Skip to main content

Advertisement

SpringerLink
Log in

Polymeric micelles and cancer therapy: an ingenious multimodal tumor-targeted drug delivery system

  • Review Article
  • Published:
Drug Delivery and Translational Research Aims and scope Submit manuscript

Abstract

Since the beginning of pharmaceutical research, drug delivery methods have been an integral part of it. Polymeric micelles (PMs) have emerged as multifunctional nanoparticles in the current technological era of nanocarriers, and they have shown promise in a range of scientific fields. They can alter the release profile of integrated pharmacological substances and concentrate them in the target zone due to their improved permeability and retention, making them more suitable for poorly soluble medicines. With their ability to deliver poorly soluble chemotherapeutic drugs, PMs have garnered considerable interest in cancer. As a result of their remarkable biocompatibility, improved permeability, and minimal toxicity to healthy cells, while also their capacity to solubilize a wide range of drugs in their micellar core, PMs are expected to be a successful treatment option for cancer therapy in the future. Their nano-size enables them to accumulate in the tumor microenvironment (TME) via the enhanced permeability and retention (EPR) effect. In this review, our major aim is to focus primarily on the stellar applications of PMs in the field of cancer therapeutics along with its mechanism of action and its latest advancements in drug and gene delivery (DNA/siRNA) for cancer, using various therapeutic strategies such as crossing blood–brain barrier, gene therapy, photothermal therapy (PTT), and immunotherapy. Furthermore, PMs can be employed as “smart drug carriers,” allowing them to target specific cancer sites using a variety of stimuli (endogenous and exogenous), which improve the specificity and efficacy of micelle-based targeted drug delivery. All the many types of stimulants, as well as how the complex of PM and various anticancer drugs react to it, and their pharmacodynamics are also reviewed here. In conclusion, commercializing engineered micelle nanoparticles (MNPs) for application in therapy and imaging can be considered as a potential approach to improve the therapeutic index of anticancer drugs. Furthermore, PM has stimulated intense interest in research and clinical practice, and in light of this, we have also highlighted a few PMs that have previously been approved for therapeutic use, while the majority are still being studied in clinical trials for various cancer therapies.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Availability of data and material

As this is a review article, availability of data and materials are not required for this submission.

Abbreviations

R&D:

Research and development

PK:

Pharmacokinetics

NP:

Nanoparticle

PMs:

Polymeric micelles

TME:

Tumor microenvironment

EPR:

Enhanced permeability and retention

PTT:

Photothermal therapy

MNPs:

Micelle nanoparticles

DDSs:

Drug delivery systems

VEGF:

Vascular endothelial growth factors

ACs:

Amphiphilic copolymer

DOX:

Doxorubicin

PBC:

Pluronic block copolymer

PEO:

Poly-(ethylene oxide)

PPO:

Poly-(propylene oxide)

PEG:

Polyethylene glycol

RES:

Reticuloendothelial system

PLA:

Poly(lactic acid)

CMC:

Critical micelle concentration

CAC:

Critical aggregation concentration

SSPMs:

Stimuli-sensitive PMs

GSH:

Glutathione

MMPs:

Matrix metalloproteases

ROS:

Reactive oxygen species

LCST:

Lower critical solution temperature

pNIPAAm:

Poly(N-isopropyl acrylamide)

PNVCL:

Poly(N-vinylcaprolactam

PTX:

Paclitaxel

GSSG:

Glutathione disulfide

Met-PEA-PEG:

L-methionine poly(ester amide)

RA:

Rheumatoid arthritis

CS:

Chitosan

CS-NBCF:

Chitosan-nitrobenzyl chloroformate conjugate

Pp:

Peptide linker

TAT:

Trans-activating transcriptional activator

mPEG-GSHn-PA:

Methoxypolyethylene glycol amine-glutathione-palmitic acid

UCST:

Upper critical solution temperature

ABC:

Amphiphilic block copolymers

PPy:

(P(HEMA-co-DMA)-b-P(AAm-co-AN)

PDT:

Photodynamic therapy

PCI:

Photochemical internalization

NIR:

Near-infrared

DNQ:

2-Diazo-1,2-naphthoquinone

DTX:

Docetaxel

Poly-DOX:

DOX conjugated polymer

US:

Ultrasound

MBs:

Microbubbles

Cur:

Curcumin

MgO-NPs:

Magnesium oxide nanoparticles

Fe3O4 :

Magnetite

Fe3O3 :

Maghemite

SPIONs:

Superparamagnetic iron oxide nanoparticles

MRI:

Magnetic resonance imaging

Fmoc:

Fluorenylmethyloxycarbonyl

PEG-PBLA:

Poly(ethylene glycol)- poly(beta-benzyl L-aspartate)

MDR:

Multi-drug resistance

mPEG-b-PAE:

Poly(ethylene glycol) methyl ether-b-poly(-amino esters)

(PAE-ss-mPEG):

Poly(ethylene glycol) methyl ether-grafted disulfide-poly(-amino esters)

PEG-PAAPBA-Pasp:

PEG-Poly(3-acrylamidophenylboronic acid)- L-Aspartic acid

BBB:

Blood–brain barrier

Pgp:

P-glycoprotein

CS-SA:

Stearic acid-grafted chitosan

CNS:

Central nervous system

siRNA:

Small interfering RNA

PICs:

Polyion complex

miRNA:

Micro-RNA

shRNA:

Short hairpin RNA

dsRNA:

Double-stranded RNA

RISC:

RNA induced silencing complex

AGO:

Argonaute

HSV-tk:

Herpes simplex virus-1 thymidine kinase

CDK:

Cyclin-dependent kinase

BAX2:

BCL-2 like protein

TRAIL:

TNF-related apoptosis-inducing ligand

Azo:

Azobenzene

PEI:

Polyethyleneimine

DOPE:

1,2-Dioleyl-sn-glycero-3-phosphoethanolamine

PAPD:

PEG-Azo-PEI-DOPE

CSC:

Cancer stem cell

DOTAP:

N-[1-(2,3-dioleoyloxy) propyl]-N, N, N-trimethylammonium methyl sulfate

Gd:

Gadolinium

MRCA:

Magnetic resonance coronary angiography

mPEG-b-P(DPA-DE):

Methyloxy-poly(ethylene glycol)-block-poly[dopamine-2-(dibutylamino) ethylamine-l-glutamate]

SQUID:

Superconducting quantum interference device

(P(PEGMA-co-APMA)-b-PMMA):

Poly[(poly(ethylene glycol) methyl ether methacrylate)-co-(3-aminopropyl methacrylate)]-block-poly(methylmethacrylate)

RAFT:

Reversible addition fragmentation chain transfer

TCPP:

5,10,15,20-Tetrakis (4-carboxyphenyl) porphyrin

TEM:

Transmission electron microscopy

DLS:

Dynamic light scattering

NETs:

Neuroendocrine tumors

UCNP:

Upconversion nanoparticle

PNBMA-PEG:

Poly(4,5-dimethyl-2-nitrobenzoate)-polyethylene glycol

RB:

Rose Bengal

GEM:

Gemcitabine

MTT:

Methyl thiazolyl tetrazolium

IPMs:

IR-780-loaded polymeric micelles

DSPE-PEG2000:

1,2-Distearoyl-sn-glycero-3-phosphoethanolamine- N-methoxy(polyethylene glycol)-2000

OLM-D:

Ovalbumin-loaded pH/redox dual-sensitive micellar vaccine

ASN:

Autophagy cascade amplification nanoparticle

HA-OXA:

OXA grafted hyaluronic acid prodrug

C-TFG micelles:

Autophagy sensitive micelles

DLPC :

Dilauroyl phosphatidylcholine

OVA:

Ovalbumin

DCs:

Dendritic cells

IDO:

Indoleamine-pyrrole 2,3-dioxygenase

PHMs:

Polymeric hybrid micelles

PCL-PEI:

Polycaprolactone-polyethylenimine

API:

Active pharmaceutical ingredient’s

Vd :

Volume of distribution

CL:

Total body clearance

Cmax :

Maximum plasma drug concentration

NSCLC:

Non-small cell lung cancer

PEG-b-pAsp:

Poly(ethylene glycol)-block-poly(aspartic acid)

PEG-b-pGlu:

Poly(ethylene glycol)block-poly(glutamic-acid).

References

  1. Tripathi RM, Shrivastav BR, Shrivastav A. Antibacterial and catalytic activity of biogenic gold nanoparticles synthesised by Trichoderma harzianum. IET Nanobiotechnol. 2018;12:509–13.

    Article  Google Scholar 

  2. Tripathi R, Pudake RN, Shrivastav B, Shrivastav A. Antibacterial activity of poly (vinyl alcohol)–biogenic silver nanocomposite film for food packaging material. Adv Nat Sci Nanosci Nanotechnol. 2018;9: 025020.

    Article  Google Scholar 

  3. Tripathi R, Chung SJ. Reclamation of hexavalent chromium using catalytic activity of highly recyclable biogenic Pd (0) nanoparticles. Sci Rep. 2020;10:1–14.

    Article  Google Scholar 

  4. Mehrotra N, Tripathi RM, Zafar F, Singh MP. Catalytic degradation of dichlorvos using biosynthesized zero valent iron nanoparticles. IEEE Trans Nanobiosci. 2017;16:280–6.

    Article  Google Scholar 

  5. Agarwal M, Bhadwal AS, Kumar N, Shrivastav A, Shrivastav BR, Singh MP, et al. Catalytic degradation of methylene blue by biosynthesised copper nanoflowers using F. benghalensis leaf extract. IET Nanobiotechnol. 2016;10:321–5.

    Article  Google Scholar 

  6. Tripathi RM, Gupta RK, Bhadwal AS, Singh P, Shrivastav A, Shrivastav B. Fungal biomolecules assisted biosynthesis of Au–Ag alloy nanoparticles and evaluation of their catalytic property. IET Nanobiotechnol. 2015;9:178–83.

    Article  Google Scholar 

  7. Tripathi R, Bhadwal AS, Gupta RK, Singh P, Shrivastav A, Shrivastav B. ZnO nanoflowers: novel biogenic synthesis and enhanced photocatalytic activity. J Photochem Photobiol B. 2014;141:288–95.

    Article  CAS  Google Scholar 

  8. Tripathi R, Kumar N, Bhadwal AS, Gupta RK, Shrivastav B, Shrivastav A. Facile and rapid biomimetic approach for synthesis of HAp nanofibers and evaluation of their photocatalytic activity. Mater Lett. 2015;140:64–7.

    Article  CAS  Google Scholar 

  9. Tripathi RM, Ahn D, Kim YM, Chung SJ. Enzyme mimetic activity of ZnO-Pd nanosheets synthesized via a green route. Molecules. 2020;25:2585.

    Article  CAS  Google Scholar 

  10. Tripathi RM, Chung SJ. Phytosynthesis of palladium nanoclusters: an efficient nanozyme for ultrasensitive and selective detection of reactive oxygen species. Molecules. 2020;25:3349.

    Article  CAS  Google Scholar 

  11. Tripathi RM, Chung SJ. Eco-friendly synthesis of SnO2-Cu nanocomposites and evaluation of their peroxidase mimetic activity. Nanomaterials. 2021;11:1798.

    Article  CAS  Google Scholar 

  12. Tripathi R, Park SH, Kim G, Kim D-H, Ahn D, Kim YM, et al. Metal-induced redshift of optical spectra of gold nanoparticles: An instant, sensitive, and selective visual detection of lead ions. Int Biodeterior Biodegradation. 2019;144: 104740.

    Article  CAS  Google Scholar 

  13. Tripathi R, Gupta RK, Singh P, Bhadwal AS, Shrivastav A, Kumar N, et al. Ultra-sensitive detection of mercury (II) ions in water sample using gold nanoparticles synthesized by Trichoderma harzianum and their mechanistic approach. Sens Actuators B Chem. 2014;204:637–46.

    Article  CAS  Google Scholar 

  14. Tripathi RM, Sharma P. Gold nanoparticles-based point-of-care colorimetric diagnostic for plant diseases. In: Biosensors in Agriculture: Recent Trends and Future Perspectives. Springer; 2021. p. 191–204.

    Chapter  Google Scholar 

  15. Safari J, Zarnegar Z. Advanced drug delivery systems: nanotechnology of health design. A review J Saudi Chem Soc. 2014;18:85–99.

    Article  CAS  Google Scholar 

  16. Tripathi R, Shrivastav A, Shrivastav B. Biogenic gold nanoparticles: as a potential candidate for brain tumor directed drug delivery. Arti Cells Nanomed Biotechnol. 2015;43:311–7.

    Article  CAS  Google Scholar 

  17. Mehrotra N, Tripathi RM. Short interfering RNA therapeutics: nanocarriers, prospects and limitations. IET Nanobiotechnol. 2015;9:386–95.

    Article  Google Scholar 

  18. Tripathi R, Chung SJ. Biogenic nanomaterials: Synthesis, characterization, growth mechanism, and biomedical applications. J Microbiol Methods. 2019;157:65–80.

    Article  CAS  Google Scholar 

  19. Movassaghian S, Merkel OM, Torchilin VP. Applications of polymer micelles for imaging and drug delivery. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2015;7:691–707.

    Article  CAS  Google Scholar 

  20. Qu Y, Chu B, Shi K, Peng J, Qian Z. Recent progress in functional micellar carriers with intrinsic therapeutic activities for anticancer drug delivery. J Biomed Nanotechnol. 2017;13:1598–618.

    Article  CAS  Google Scholar 

  21. Aly HA. Cancer therapy and vaccination. J Immunol Methods. 2012;382:1–23.

    Article  CAS  Google Scholar 

  22. Zhou Q, Zhang L, Yang T, Wu H. Stimuli-responsive polymeric micelles for drug delivery and cancer therapy. Int J Nanomed. 2018;13:2921.

    Article  CAS  Google Scholar 

  23. Rao NV, Ko H, Lee J, Park JH. Recent progress and advances in stimuli-responsive polymers for cancer therapy. Front Bioeng Biotechnol. 2018;6:110.

    Article  Google Scholar 

  24. Muller RH, Keck CM. Challenges and solutions for the delivery of biotech drugs–a review of drug nanocrystal technology and lipid nanoparticles. J Biotechnol. 2004;113:151–70.

    Article  CAS  Google Scholar 

  25. Zheng X, Xie J, Zhang X, Sun W, Zhao H, Li Y, et al. An overview of polymeric nanomicelles in clinical trials and on the market. Chin Chem Lett. 2021;32:243–57.

    Article  CAS  Google Scholar 

  26. Trédan O, Galmarini CM, Patel K, Tannock IF. Drug resistance and the solid tumor microenvironment. J Natl Cancer Inst. 2007;99:1441–54.

    Article  Google Scholar 

  27. Vasan N, Baselga J, Hyman DM. A view on drug resistance in cancer. Nature. 2019;575:299–309.

    Article  CAS  Google Scholar 

  28. Tran S, DeGiovanni P, Piel B, Rai P. Cancer nanomedicine: a review of recent success in drug delivery. Clin Transl Med. 2017;6:44.

    Article  Google Scholar 

  29. Marzbali MY, Khosroushahi AY. Polymeric micelles as mighty nanocarriers for cancer gene therapy: a review. Cancer Chemother Pharmacol. 2017;79:637–49.

    Article  Google Scholar 

  30. Cho H, Lai TC, Tomoda K, Kwon GS. Polymeric micelles for multi-drug delivery in cancer. AAPS PharmSciTech. 2015;16:10–20.

    Article  CAS  Google Scholar 

  31. Gaucher G, Satturwar P, Jones M-C, Furtos A, Leroux J-C. Polymeric micelles for oral drug delivery. Eur J Pharm Biopharm. 2010;76:147–58.

    Article  CAS  Google Scholar 

  32. Luschmann C, Tessmar J, Schoeberl S, Strau O, Luschmann K, Goepferich A. Self-assembling colloidal system for the ocular administration of cyclosporine A. Cornea. 2014;33:77–81.

    Article  Google Scholar 

  33. Kanazawa T, Morisaki K, Suzuki S, Takashima Y. Prolongation of life in rats with malignant glioma by intranasal siRNA/drug codelivery to the brain with cell-penetrating peptide-modified micelles. Mol Pharm. 2014;11:1471–8.

    Article  CAS  Google Scholar 

  34. Richter A, Olbrich C, Krause M, Hoffmann J, Kissel T. Polymeric micelles for parenteral delivery of sagopilone: physicochemical characterization, novel formulation approaches and their toxicity assessment in vitro as well as in vivo. Eur J Pharm Biopharm. 2010;75:80–9.

    Article  CAS  Google Scholar 

  35. Maeda H, Wu J, Sawa T, Matsumura Y, Hori K. Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Control Release. 2000;65:271–84.

    Article  CAS  Google Scholar 

  36. Cabral H, Matsumoto Y, Mizuno K, Chen Q, Murakami M, Kimura M, et al. Accumulation of sub-100 nm polymeric micelles in poorly permeable tumours depends on size. Nat Nanotechnol. 2011;6:815–23.

    Article  CAS  Google Scholar 

  37. Li Y, Xiao K, Zhu W, Deng W, Lam KS. Stimuli-responsive cross-linked micelles for on-demand drug delivery against cancers. Adv Drug Deliv Rev. 2014;66:58–73.

    Article  CAS  Google Scholar 

  38. Nakayama M, Akimoto J, Okano T. Polymeric micelles with stimuli-triggering systems for advanced cancer drug targeting. J Drug Target. 2014;22:584–99.

    Article  CAS  Google Scholar 

  39. Chaturvedi VK, Singh A, Singh VK, Singh MP. Cancer nanotechnology: a new revolution for cancer diagnosis and therapy. Curr Drug Metab. 2019;20:416–29.

    Article  CAS  Google Scholar 

  40. Rana S, Bhattacharjee J, Barick KC, Verma G, Hassan PA, Yakhmi JV. Interfacial engineering of nanoparticles for cancer therapeutics. Nanostructures for Cancer Therapy: Elsevier; 2017. p. 177–209.

    Google Scholar 

  41. Parveen S, Misra R, Sahoo SK. Nanoparticles: a boon to drug delivery, therapeutics, diagnostics and imaging. Nanomed Nanotechnol Biol Med. 2012;8:147–66.

    Article  CAS  Google Scholar 

  42. Pathak C, Vaidya FU, Pandey SM. Mechanism for development of nanobased drug delivery system. In: Applications of Targeted Nano Drugs and Delivery Systems. Elsevier; 2019. p. 35–67.

    Chapter  Google Scholar 

  43. Bhattacharjee J, Verma G, Aswal V, Hassan P. Small angle neutron scattering study of doxorubicin-surfactant complexes encapsulated in block copolymer micelles. Pramana. 2008;71:991–5.

    Article  CAS  Google Scholar 

  44. Jhaveri AM, Torchilin VP. Multifunctional polymeric micelles for delivery of drugs and siRNA. Front Pharmacol. 2014;5:77.

    Article  Google Scholar 

  45. Li Y, Gao J, Zhang C, Cao Z, Cheng D, Liu J, et al. Stimuli-responsive polymeric nanocarriers for efficient gene delivery. In: Polymeric Gene Delivery Systems. Springer; 2017. p. 167–215.

    Chapter  Google Scholar 

  46. Alfurhood JA, Sun H, Kabb CP, Tucker BS, Matthews JH, Luesch H, et al. Poly (N-(2-hydroxypropyl) methacrylamide)–valproic acid conjugates as block copolymer nanocarriers. Polym Chem. 2017;8:4983–7.

    Article  CAS  Google Scholar 

  47. Rabanel J-M, Faivre J, Tehrani SF, Lalloz A, Hildgen P, Banquy X. Effect of the polymer architecture on the structural and biophysical properties of PEG–PLA nanoparticles. ACS Appl Mater Interfaces. 2015;7:10374–85.

    Article  CAS  Google Scholar 

  48. Mishra S, De A, Mozumdar S. Synthesis of thermoresponsive polymers for drug delivery. Drug Delivery System: Springer; 2014. p. 77–101.

    Google Scholar 

  49. Xiong W, Peng L, Chen H, Li Q. Surface modification of MPEG-b-PCL-based nanoparticles via oxidative self-polymerization of dopamine for malignant melanoma therapy. Int J Nanomed. 2015;10:2985.

    CAS  Google Scholar 

  50. Li Z, Tan S, Li S, Shen Q, Wang K. Cancer drug delivery in the nano era: an overview and perspectives. Oncol Rep. 2017;38:611–24.

    Article  CAS  Google Scholar 

  51. Xu W, Ling P, Zhang T. Polymeric micelles, a promising drug delivery system to enhance bioavailability of poorly water-soluble drugs. J Drug Deliv. 2013;2013:340315.

    Article  Google Scholar 

  52. Sharma AK, Zhang L, Li S, Kelly DL, Alakhov VY, Batrakova EV, et al. Prevention of MDR development in leukemia cells by micelle-forming polymeric surfactant. J Control Release. 2008;131:220–7.

    Article  CAS  Google Scholar 

  53. Kanazawa T, Sugawara K, Tanaka K, Horiuchi S, Takashima Y, Okada H. Suppression of tumor growth by systemic delivery of anti-VEGF siRNA with cell-penetrating peptide-modified MPEG–PCL nanomicelles. Eur J Pharm Biopharm. 2012;81:470–7.

    Article  CAS  Google Scholar 

  54. Laouini A, Koutroumanis KP, Charcosset C, Georgiadou S, Fessi H, Holdich RG, et al. pH-Sensitive micelles for targeted drug delivery prepared using a novel membrane contactor method. ACS Appl Mater Interfaces. 2013;5:8939–47.

    Article  CAS  Google Scholar 

  55. Koyamatsu Y, Hirano T, Kakizawa Y, Okano F, Takarada T, Maeda M. pH-responsive release of proteins from biocompatible and biodegradable reverse polymer micelles. J Control Release. 2014;173:89–95.

    Article  CAS  Google Scholar 

  56. Kagaya H, Oba M, Miura Y, Koyama H, Ishii T, Shimada T, et al. Impact of polyplex micelles installed with cyclic RGD peptide as ligand on gene delivery to vascular lesions. Gene Ther. 2012;19:61–9.

    Article  CAS  Google Scholar 

  57. Wu H, Zhu L, Torchilin VP. pH-sensitive poly (histidine)-PEG/DSPE-PEG co-polymer micelles for cytosolic drug delivery. Biomaterials. 2013;34:1213–22.

    Article  CAS  Google Scholar 

  58. Min KH, Kim J-H, Bae SM, Shin H, Kim MS, Park S, et al. Tumoral acidic pH-responsive MPEG-poly (β-amino ester) polymeric micelles for cancer targeting therapy. J Control Release. 2010;144:259–66.

    Article  CAS  Google Scholar 

  59. Perche F, Patel NR, Torchilin VP. Accumulation and toxicity of antibody-targeted doxorubicin-loaded PEG–PE micelles in ovarian cancer cell spheroid model. J Control Release. 2012;164:95–102.

    Article  CAS  Google Scholar 

  60. Sawant RR, Jhaveri AM, Koshkaryev A, Qureshi F, Torchilin VP. The effect of dual ligand-targeted micelles on the delivery and efficacy of poorly soluble drug for cancer therapy. J Drug Target. 2013;21:630–8.

    Article  CAS  Google Scholar 

  61. Salzano G, Riehle R, Navarro G, Perche F, De Rosa G, Torchilin V. Polymeric micelles containing reversibly phospholipid-modified anti-survivin siRNA: a promising strategy to overcome drug resistance in cancer. Cancer Lett. 2014;343:224–31.

    Article  CAS  Google Scholar 

  62. Palazzolo S, Bayda S, Hadla M, Caligiuri I, Corona G, Toffoli G, et al. The clinical translation of organic nanomaterials for cancer therapy: a focus on polymeric nanoparticles, micelles, liposomes and exosomes. Curr Med Chem. 2018;25:4224–68.

    Article  CAS  Google Scholar 

  63. Sarisozen C, Joshi U, Mendes LP, Torchilin VP. Stimuli-responsive polymeric micelles for extracellular and intracellular drug delivery. Stimuli Responsive Polymeric Nanocarriers for Drug Delivery Applications: Elsevier; 2019. p. 269–304.

    Google Scholar 

  64. Kulthe SS, Choudhari YM, Inamdar NN, Mourya V. Polymeric micelles: authoritative aspects for drug delivery. Des Monomers Polym. 2012;15:465–521.

    Article  CAS  Google Scholar 

  65. Mura S, Nicolas J, Couvreur P. Stimuli-responsive nanocarriers for drug delivery. Nat Mater. 2013;12:991–1003.

    Article  CAS  Google Scholar 

  66. Dai Y, Chen X, Zhang X. Recent advances in stimuli-responsive polymeric micelles via click chemistry. Polym Chem. 2019;10:34–44.

    Article  CAS  Google Scholar 

  67. Biswas S, Kumari P, Lakhani PM, Ghosh B. Recent advances in polymeric micelles for anti-cancer drug delivery. Eur J Pharm Sci. 2016;83:184–202.

    Article  CAS  Google Scholar 

  68. Liu D, Yang F, Xiong F, Gu N. The smart drug delivery system and its clinical potential. Theranostics. 2016;6:1306.

    Article  CAS  Google Scholar 

  69. Hu X, Tian J, Liu T, Zhang G, Liu S. Photo-triggered release of caged camptothecin prodrugs from dually responsive shell cross-linked micelles. Macromolecules. 2013;46:6243–56.

    Article  CAS  Google Scholar 

  70. Basel MT, Shrestha TB, Troyer DL, Bossmann SH. Protease-sensitive, polymer-caged liposomes: a method for making highly targeted liposomes using triggered release. ACS Nano. 2011;5:2162–75.

    Article  CAS  Google Scholar 

  71. Li J, Ma YJ, Wang Y, Chen BZ, Guo XD, Zhang CY. Dual redox/pH-responsive hybrid polymer-lipid composites: Synthesis, preparation, characterization and application in drug delivery with enhanced therapeutic efficacy. Chem Eng J. 2018;341:450–61.

    Article  CAS  Google Scholar 

  72. Qiu N, Du X, Ji J, Zhai G. A review of stimuli-responsive polymeric micelles for tumor-targeted delivery of curcumin. Drug Dev Ind Pharm. 2021;47:839–56.

    Article  CAS  Google Scholar 

  73. Raza A, Hayat U, Rasheed T, Bilal M, Iqbal HM. “Smart” materials-based near-infrared light-responsive drug delivery systems for cancer treatment: a review. J Market Res. 2019;8:1497–509.

    CAS  Google Scholar 

  74. Deepak P, Nagaich U, Sharma A, Gulati N, Chaudhary A. Polymeric micelles: potential drug delivery devices. Indones J Pharm. 2013;24:222–37.

    Google Scholar 

  75. Akimoto J, Nakayama M, Okano T. Temperature-responsive polymeric micelles for optimizing drug targeting to solid tumors. J Control Release. 2014;193:2–8.

    Article  CAS  Google Scholar 

  76. Cortez-Lemus NA, Licea-Claverie A. Poly (N-vinylcaprolactam), a comprehensive review on a thermoresponsive polymer becoming popular. Prog Polym Sci. 2016;53:1–51.

    Article  CAS  Google Scholar 

  77. Rao NV, Yoon HY, Han HS, Ko H, Son S, Lee M, et al. Recent developments in hyaluronic acid-based nanomedicine for targeted cancer treatment. Expert Opin Drug Deliv. 2016;13:239–52.

    Article  CAS  Google Scholar 

  78. Kocak G, Tuncer C. Bütün V. pH-Responsive polymers. Polym Chem. 2017;8:144–76.

    Article  CAS  Google Scholar 

  79. Cairns RA, Harris IS, Mak TW. Regulation of cancer cell metabolism. Nat Rev Cancer. 2011;11:85–95.

    Article  CAS  Google Scholar 

  80. Liu Y, Wang W, Yang J, Zhou C, Sun J. pH-sensitive polymeric micelles triggered drug release for extracellular and intracellular drug targeting delivery. Asian J Pharm Sci. 2013;8:159–67.

    Article  Google Scholar 

  81. Han Y, Pan J, Liang N, Gong X, Sun S. A pH-sensitive polymeric micellar system based on chitosan derivative for efficient delivery of paclitaxel. Int J Mol Sci. 2021;22:6659.

    Article  CAS  Google Scholar 

  82. Thambi T, Lee DS. Stimuli-responsive polymersomes for cancer therapy. In: Stimuli Responsive Polymeric Nanocarriers for Drug Delivery Applications. Elsevier; 2019. p. 413–38.

    Chapter  Google Scholar 

  83. Choi KY, Saravanakumar G, Park JH, Park K. Hyaluronic acid-based nanocarriers for intracellular targeting: interfacial interactions with proteins in cancer. Colloids Surf B. 2012;99:82–94.

    Article  CAS  Google Scholar 

  84. Sun C, Lu J, Wang J, Hao P, Li C, Qi L, et al. Redox-sensitive polymeric micelles with aggregation-induced emission for bioimaging and delivery of anticancer drugs. J Nanobiotechnol. 2021;19:1–15.

    Article  Google Scholar 

  85. Na Q, Xiyou D, Ji J, Zhai G. A review of stimuli-responsive polymeric micelles for tumor-targeted delivery of curcumin. Drug Dev Ind Pharm. 2021;47:839–56.

    Article  Google Scholar 

  86. Estrela JM, Ortega A, Obrador E. Glutathione in cancer biology and therapy. Crit Rev Clin Lab Sci. 2006;43:143–81.

    Article  CAS  Google Scholar 

  87. Cheng R, Feng F, Meng F, Deng C, Feijen J, Zhong Z. Glutathione-responsive nano-vehicles as a promising platform for targeted intracellular drug and gene delivery. J Control Release. 2011;152:2–12.

    Article  CAS  Google Scholar 

  88. Daund V, Chalke S, Sherje AP, Kale P. ROS responsive mesoporous silica nanoparticles for smart drug delivery: A review. J Drug Deliv Sci Technol. 2021;64:102599.

    Article  CAS  Google Scholar 

  89. Deng Z, Hu J, Liu S. Reactive Oxygen, Nitrogen, and Sulfur Species (RONSS)-Responsive Polymersomes for Triggered Drug Release. Macromol Rapid Commun. 2017;38:1600685.

    Article  Google Scholar 

  90. Dharmaraja AT. Role of reactive oxygen species (ROS) in therapeutics and drug resistance in cancer and bacteria. J Med Chem. 2017;60:3221–40.

    Article  CAS  Google Scholar 

  91. Lu Y, Aimetti AA, Langer R, Gu Z. Bioresponsive materials. Nat Rev Mater. 2016;2:1–17.

    Google Scholar 

  92. Xu Q, Chu CC. Development of ROS-responsive amino acid-based poly (ester amide) nanoparticle for anticancer drug delivery. J Biomed Mater Res A. 2021;109:524–37.

    Article  CAS  Google Scholar 

  93. Harris AL. Hypoxia–a key regulatory factor in tumour growth. Nat Rev Cancer. 2002;2:38–47.

    Article  CAS  Google Scholar 

  94. Cabane E, Zhang X, Langowska K, Palivan CG, Meier W. Stimuli-responsive polymers and their applications in nanomedicine. Biointerphases. 2012;7:9.

    Article  CAS  Google Scholar 

  95. Thambi T, Deepagan V, Yoon HY, Han HS, Kim S-H, Son S, et al. Hypoxia-responsive polymeric nanoparticles for tumor-targeted drug delivery. Biomaterials. 2014;35:1735–43.

    Article  CAS  Google Scholar 

  96. Brown JM, Wilson WR. Exploiting tumour hypoxia in cancer treatment. Nat Rev Cancer. 2004;4:437–47.

    Article  CAS  Google Scholar 

  97. Vaupel P, Mayer A, Höckel M. Tumor hypoxia and malignant progression. Methods Enzymol. 2004;381:335–54.

    Article  CAS  Google Scholar 

  98. Xiang L, Gilkes DM, Chaturvedi P, Luo W, Hu H, Takano N, et al. Ganetespib blocks HIF-1 activity and inhibits tumor growth, vascularization, stem cell maintenance, invasion, and metastasis in orthotopic mouse models of triple-negative breast cancer. J Mol Med. 2014;92:151–64.

    Article  CAS  Google Scholar 

  99. Chen Z, Wen W, Guo J. Hypoxia-sensitive micelles based on amphiphilic chitosan derivatives for drug-controlled release. Polym Adv Technol. 2021;32:3113–22.

    Article  CAS  Google Scholar 

  100. Chen H, Liu D, Guo Z. Endogenous stimuli-responsive nanocarriers for drug delivery. Chem Lett. 2016;45:242–9.

    Article  CAS  Google Scholar 

  101. Yao Q, Dai Z, Hoon Choi J, Kim D, Zhu L. Building stable MMP2-responsive multifunctional polymeric micelles by an all-in-one polymer–lipid conjugate for tumor-targeted intracellular drug delivery. ACS Appl Mater Interfaces. 2017;9:32520–33.

    Article  CAS  Google Scholar 

  102. Lima AC, Reis RL, Ferreira H, Neves NM. Glutathione reductase-sensitive polymeric micelles for controlled drug delivery on arthritic diseases. ACS Biomater Sci Eng. 2021;7:3229–41.

    Article  CAS  Google Scholar 

  103. Rasheed T, Bilal M, Abu-Thabit NY, Iqbal HM. The smart chemistry of stimuli-responsive polymeric carriers for target drug delivery applications. In: Stimuli Responsive Polymeric Nanocarriers for Drug Delivery Applications, vol. 1. Elsevier; 2018. p. 61–99.

    Chapter  Google Scholar 

  104. Napoli A, Valentini M, Tirelli N, Müller M, Hubbell JA. Oxidation-responsive polymeric vesicles. Nat Mater. 2004;3:183–9.

    Article  CAS  Google Scholar 

  105. Yang J, Zhai S, Qin H, Yan H, Xing D, Hu X. NIR-controlled morphology transformation and pulsatile drug delivery based on multifunctional phototheranostic nanoparticles for photoacoustic imaging-guided photothermal-chemotherapy. Biomaterials. 2018;176:1–12.

    Article  CAS  Google Scholar 

  106. Brown AA, Azzaroni O, Huck WT. Photoresponsive polymer brushes for hydrophilic patterning. Langmuir. 2009;25:1744–9.

    Article  CAS  Google Scholar 

  107. Hossion AM, Bio M, Nkepang G, Awuah SG, You Y. Visible light controlled release of anticancer drug through double activation of prodrug. ACS Med Chem Lett. 2013;4:124–7.

    Article  CAS  Google Scholar 

  108. Liu C, Zhang Y, Liu M, Chen Z, Lin Y, Li W, et al. A NIR-controlled cage mimicking system for hydrophobic drug mediated cancer therapy. Biomaterials. 2017;139:151–62.

    Article  CAS  Google Scholar 

  109. Zhao Y. Rational design of light-controllable polymer micelles. Chem Rec. 2007;7:286–94.

    Article  CAS  Google Scholar 

  110. Schumers JM, Fustin CA, Gohy JF. Light-responsive block copolymers. Macromol Rapid Commun. 2010;31:1588–607.

    Article  CAS  Google Scholar 

  111. Zhao Y-L, Stoddart JF. Azobenzene-based light-responsive hydrogel system. Langmuir. 2009;25:8442–6.

    Article  CAS  Google Scholar 

  112. Cui J, Del Campo A. Photo-responsive polymers: properties, synthesis and applications. Smart polymers and their applications: Elsevier; 2014. p. 93–133.

    Google Scholar 

  113. Chen J, Qian C, Ren P, Yu H, Kong X, Huang C, et al. Light-Responsive Micelles Loaded With Doxorubicin for Osteosarcoma Suppression. Front Pharmacol. 2021;12:1378.

    Google Scholar 

  114. Yadav HK, Mohammed A, Dibi M. Advancements in exogeneous techniques for stimuli-sensitive delivery systems. Drug Targeting and Stimuli Sensitive Drug Delivery Systems: Elsevier; 2018. p. 447–81.

    Google Scholar 

  115. Ahmed SE, Martins AM, Husseini GA. The use of ultrasound to release chemotherapeutic drugs from micelles and liposomes. J Drug Target. 2015;23:16–42.

    Article  CAS  Google Scholar 

  116. Wu P, Jia Y, Qu F, Sun Y, Wang P, Zhang K, et al. Ultrasound-responsive polymeric micelles for sonoporation-assisted site-specific therapeutic action. ACS Appl Mater Interfaces. 2017;9:25706–16.

    Article  CAS  Google Scholar 

  117. Li Y, Zhang H, Zhai G-X. Intelligent polymeric micelles: development and application as drug delivery for docetaxel. J Drug Target. 2017;25:285–95.

    Article  CAS  Google Scholar 

  118. Gupta AK, Naregalkar RR, Vaidya VD, Gupta M. Recent advances on surface engineering of magnetic iron oxide nanoparticles and their biomedical applications. Nanomedicine. 2007;2:23–39.

    Article  CAS  Google Scholar 

  119. Wang Y, Kohane DS. External triggering and triggered targeting strategies for drug delivery. Nat Rev Mater. 2017;2:1–14.

    Article  Google Scholar 

  120. Schleich N, Danhier F, Préat V. Iron oxide-loaded nanotheranostics: Major obstacles to in vivo studies and clinical translation. J Control Release. 2015;198:35–54.

    Article  CAS  Google Scholar 

  121. Jeon G, Yang SY, Byun J, Kim JK. Electrically actuatable smart nanoporous membrane for pulsatile drug release. Nano Lett. 2011;11:1284–8.

    Article  CAS  Google Scholar 

  122. Servant A, Bussy C, Al-Jamal K, Kostarelos K. Design, engineering and structural integrity of electro-responsive carbon nanotube-based hydrogels for pulsatile drug release. J Mater Chem B. 2013;1:4593–600.

    Article  CAS  Google Scholar 

  123. Ge J, Neofytou E, Cahill TJ III, Beygui RE, Zare RN. Drug release from electric-field-responsive nanoparticles. ACS Nano. 2012;6:227–33.

    Article  CAS  Google Scholar 

  124. Song K, Wang Z, Liu X, Zhang G, Wang X, Ouyang D, et al. A novel dual sensitive polymer-gambogic acid conjugate: synthesis, characterization, and in vitro evaluation. Nanotechnology. 2019;30: 505701.

    Article  CAS  Google Scholar 

  125. Pamfil D, Vasile C. Responsive polymeric nanotherapeutics. In: Polymeric nanomaterials in nanotherapeutics. Elsevier; 2019. p. 67–121.

    Chapter  Google Scholar 

  126. Cheng R, Meng F, Deng C, Klok H-A, Zhong Z. Dual and multi-stimuli responsive polymeric nanoparticles for programmed site-specific drug delivery. Biomaterials. 2013;34:3647–57.

    Article  CAS  Google Scholar 

  127. Savić R, Eisenberg A, Maysinger D. Block copolymer micelles as delivery vehicles of hydrophobic drugs: micelle–cell interactions. J Drug Target. 2006;14:343–55.

    Article  Google Scholar 

  128. Gill KK, Nazzal S, Kaddoumi A. Paclitaxel loaded PEG5000–DSPE micelles as pulmonary delivery platform: formulation characterization, tissue distribution, plasma pharmacokinetics, and toxicological evaluation. Eur J Pharm Biopharm. 2011;79:276–84.

    Article  CAS  Google Scholar 

  129. Moses MA, Brem H, Langer R. Advancing the field of drug delivery: taking aim at cancer. Cancer Cell. 2003;4:337–41.

    Article  CAS  Google Scholar 

  130. Doppalapudi S, Jain A, Domb AJ, Khan W. Biodegradable polymers for targeted delivery of anti-cancer drugs. Expert Opin Drug Deliv. 2016;13:891–909.

    Article  CAS  Google Scholar 

  131. Majumder N, G Das N, Das SK. Polymeric micelles for anticancer drug delivery. Ther Deliv. 2020;11:613–35.

    Article  CAS  Google Scholar 

  132. Latere Dwan’Isa J-P, Rouxhet L, Préat V, Brewster M, Arien A. Prediction of drug solubility in amphiphilic di-block copolymer micelles: the role of polymer-drug compatibility. Pharmazie Int J Pharm Sci. 2007;62:499–504.

    CAS  Google Scholar 

  133. Kim JY, Kim S, Papp M, Park K, Pinal R. Hydrotropic solubilization of poorly water-soluble drugs. J Pharm Sci. 2010;99:3953–65.

    Article  CAS  Google Scholar 

  134. Zhang Y, Huang Y, Li S. Polymeric micelles: nanocarriers for cancer-targeted drug delivery. AAPS PharmSciTech. 2014;15:862–71.

    Article  CAS  Google Scholar 

  135. Yang C, Attia ABE, Tan JP, Ke X, Gao S, Hedrick JL, et al. The role of non-covalent interactions in anticancer drug loading and kinetic stability of polymeric micelles. Biomaterials. 2012;33:2971–9.

    Article  CAS  Google Scholar 

  136. Zhang H, Mi P. Polymeric micelles for tumor theranostics. Theranostic Bionanomaterials: Elsevier; 2019. p. 289–302.

    Google Scholar 

  137. Kaur J, Mishra V, Singh SK, Gulati M, Kapoor B, Chellappan DK, et al. Harnessing amphiphilic polymeric micelles for diagnostic and therapeutic applications: Breakthroughs and bottlenecks. J Control Release. 2021;334:64–95.

    Article  CAS  Google Scholar 

  138. Matsumura Y. Preclinical and clinical studies of NK012, an SN-38-incorporating polymeric micelles, which is designed based on EPR effect. Adv Drug Deliv Rev. 2011;63:184–92.

    Article  CAS  Google Scholar 

  139. Attia MF, Anton N, Wallyn J, Omran Z, Vandamme TF. An overview of active and passive targeting strategies to improve the nanocarriers efficiency to tumour sites. J Pharm Pharmacol. 2019;71:1185–98.

    Article  CAS  Google Scholar 

  140. Torchilin V. Targeted polymeric micelles for delivery of poorly soluble drugs. Cell Mol Life Sci. 2004;61:2549–59.

    Article  CAS  Google Scholar 

  141. Bae YH. Drug targeting and tumor heterogeneity. J Control Release. 2009;133:2.

    Article  CAS  Google Scholar 

  142. Wicki A, Witzigmann D, Balasubramanian V, Huwyler J. Nanomedicine in cancer therapy: challenges, opportunities, and clinical applications. J Control Release. 2015;200:138–57.

    Article  CAS  Google Scholar 

  143. Wang N, Chen X-C, Ding R-L, Yang X-L, Li J, Yu X-Q, et al. Synthesis of high drug loading, reactive oxygen species and esterase dual-responsive polymeric micelles for drug delivery. RSC Adv. 2019;9:2371–8.

    Article  CAS  Google Scholar 

  144. Costa SA, Mozhdehi D, Dzuricky MJ, Isaacs FJ, Brustad EM, Chilkoti A. Active targeting of cancer cells by nanobody decorated polypeptide micelle with bio-orthogonally conjugated drug. Nano Lett. 2018;19:247–54.

    Article  Google Scholar 

  145. Xie Y-T, Du Y-Z, Yuan H, Hu F-Q. Brain-targeting study of stearic acid–grafted chitosan micelle drug-delivery system. Int J Nanomed. 2012;7:3235.

    CAS  Google Scholar 

  146. Sardoiwala MN, Kaundal B, Choudhury SR. Development of engineered nanoparticles expediting diagnostic and therapeutic applications across blood–brain barrier. In: Handbook of Nanomaterials for Industrial Applications. Elsevier; 2018. p. 696–709.

    Chapter  Google Scholar 

  147. Hu F-Q, Ren G-F, Yuan H, Du Y-Z, Zeng S. Shell cross-linked stearic acid grafted chitosan oligosaccharide self-aggregated micelles for controlled release of paclitaxel. Colloids Surf B. 2006;50:97–103.

    Article  CAS  Google Scholar 

  148. Batrakova EV, Zhang Y, Li Y, Li S, Vinogradov SV, Persidsky Y, et al. Effects of pluronic P85 on GLUT1 and MCT1 transporters in the blood-brain barrier. Pharm Res. 2004;21:1993–2000.

    Article  CAS  Google Scholar 

  149. Torchilin VP. Nanoparticulates as drug carriers. Imperial College Press; 2006.

    Book  Google Scholar 

  150. Rao KS, Ghorpade A, Labhasetwar V. Targeting anti-HIV drugs to the CNS. Expert Opin Drug Deliv. 2009;6:771–84.

    Article  CAS  Google Scholar 

  151. Wohlfart S, Khalansky AS, Gelperina S, Begley D, Kreuter J. Kinetics of transport of doxorubicin bound to nanoparticles across the blood–brain barrier. J Control Release. 2011;154:103–7.

    Article  CAS  Google Scholar 

  152. Navarro G, Pan J, Torchilin VP. Micelle-like nanoparticles as carriers for DNA and siRNA. Mol Pharm. 2015;12:301–13.

    Article  CAS  Google Scholar 

  153. Liu XQ, Sun CY, Yang XZ, Wang J. Polymeric-micelle-based nanomedicine for siRNA delivery. Part Part Syst Charact. 2013;30:211–28.

    Article  CAS  Google Scholar 

  154. Wang K, Kievit FM, Zhang M. Nanoparticles for cancer gene therapy: recent advances, challenges, and strategies. Pharmacol Res. 2016;114:56–66.

    Article  CAS  Google Scholar 

  155. Ameres SL, Martinez J, Schroeder R. Molecular basis for target RNA recognition and cleavage by human RISC. Cell. 2007;130:101–12.

    Article  CAS  Google Scholar 

  156. Amjad MW, Kesharwani P, Amin MCIM, Iyer AK. Recent advances in the design, development, and targeting mechanisms of polymeric micelles for delivery of siRNA in cancer therapy. Prog Polym Sci. 2017;64:154–81.

    Article  CAS  Google Scholar 

  157. Bader A, Brown D, Stoudemire J, Lammers P. Developing therapeutic microRNAs for cancer. Gene Ther. 2011;18:1121–6.

    Article  CAS  Google Scholar 

  158. Joshi U, Filipczak N, Khan MM, Attia SA, Torchilin V. Hypoxia-sensitive micellar nanoparticles for co-delivery of siRNA and chemotherapeutics to overcome multi-drug resistance in tumor cells. Int J Pharm. 2020;590: 119915.

    Article  CAS  Google Scholar 

  159. Rafael D, Gener P, Andrade F, Seras-Franzoso J, Montero S, Fernández Y, et al. AKT2 siRNA delivery with amphiphilic-based polymeric micelles show efficacy against cancer stem cells. Drug Delivery. 2018;25:961–72.

    Article  CAS  Google Scholar 

  160. Lu Y, Zhong L, Jiang Z, Pan H, Zhang Y, Zhu G, et al. Cationic micelle-based siRNA delivery for efficient colon cancer gene therapy. Nanoscale Res Lett. 2019;14:1–9.

    Article  Google Scholar 

  161. Wang H, Ding S, Zhang Z, Wang L, You Y. Cationic micelle: a promising nanocarrier for gene delivery with high transfection efficiency. J Gene Med. 2019;21: e3101.

    Article  Google Scholar 

  162. Yi N, Oh B, Kim HA, Lee M. Combined delivery of BCNU and VEGF siRNA using amphiphilic peptides for glioblastoma. J Drug Target. 2014;22:156–64.

    Article  CAS  Google Scholar 

  163. Zhou X, Zheng Q, Wang C, Xu J, Wu J-P, Kirk TB, et al. Star-shaped amphiphilic hyperbranched polyglycerol conjugated with dendritic poly (L-lysine) for the codelivery of docetaxel and MMP-9 siRNA in cancer therapy. ACS Appl Mater Interfaces. 2016;8:12609–19.

    Article  CAS  Google Scholar 

  164. Zhang CG, Zhu WJ, Liu Y, Yuan ZQ, Yang SD, Chen WL, et al. Novel polymer micelle mediated co-delivery of doxorubicin and P-glycoprotein siRNA for reversal of multidrug resistance and synergistic tumor therapy. Sci Rep. 2016;6:1–12.

    Google Scholar 

  165. Yao C, Liu J, Wu X, Tai Z, Gao Y, Zhu Q, et al. Reducible self-assembling cationic polypeptide-based micelles mediate co-delivery of doxorubicin and microRNA-34a for androgen-independent prostate cancer therapy. J Control Release. 2016;232:203–14.

    Article  CAS  Google Scholar 

  166. Kim TH, Mount CW, Dulken BW, Ramos J, Fu CJ, Khant HA, et al. Filamentous, mixed micelles of triblock copolymers enhance tumor localization of indocyanine green in a murine xenograft model. Mol Pharm. 2012;9:135–43.

    Article  CAS  Google Scholar 

  167. Zhang X, Chen D, Ba S, Chang J, Zhou J, Zhao H, et al. Poly (l-histidine) based copolymers: effect of the chemically substituted l-histidine on the physio-chemical properties of the micelles and in vivo biodistribution. Colloids Surf B. 2016;140:176–84.

    Article  CAS  Google Scholar 

  168. Yang H, Mao H, Wan Z, Zhu A, Guo M, Li Y, et al. Micelles assembled with carbocyanine dyes for theranostic near-infrared fluorescent cancer imaging and photothermal therapy. Biomaterials. 2013;34:9124–33.

    Article  CAS  Google Scholar 

  169. Yang HY, Jang M-S, Gao GH, Lee JH, Lee DS. pH-Responsive biodegradable polymeric micelles with anchors to interface magnetic nanoparticles for MR imaging in detection of cerebral ischemic area. Nanoscale. 2016;8:12588–98.

    Article  CAS  Google Scholar 

  170. Liu X, Yang G, Zhang L, Liu Z, Cheng Z, Zhu X. Photosensitizer cross-linked nano-micelle platform for multimodal imaging guided synergistic photothermal/photodynamic therapy. Nanoscale. 2016;8:15323–39.

    Article  CAS  Google Scholar 

  171. Chen G, Jaskula-Sztul R, Esquibel CR, Lou I, Zheng Q, Dammalapati A, et al. Neuroendocrine tumor-targeted upconversion nanoparticle-based micelles for simultaneous nir-controlled combination chemotherapy and photodynamic therapy, and fluorescence imaging. Adv Func Mater. 2017;27:1604671.

    Article  Google Scholar 

  172. Han H, Wang H, Chen Y, Li Z, Wang Y, Jin Q, et al. Theranostic reduction-sensitive gemcitabine prodrug micelles for near-infrared imaging and pancreatic cancer therapy. Nanoscale. 2016;8:283–91.

    Article  CAS  Google Scholar 

  173. He B, Hu HY, Tan T, Wang H, Sun KX, Li YP, et al. IR-780-loaded polymeric micelles enhance the efficacy of photothermal therapy in treating breast cancer lymphatic metastasis in mice. Acta Pharmacol Sin. 2018;39:132–9.

    Article  CAS  Google Scholar 

  174. Cheng C-T, Castro G, Liu C-H, Lau P. Advanced nanotechnology: an arsenal to enhance immunotherapy in fighting cancer. Clin Chim Acta. 2019;492:12–9.

    Article  CAS  Google Scholar 

  175. Poilil Surendran S, Moon MJ, Park R, Jeong YY. Bioactive nanoparticles for cancer immunotherapy. Int J Mol Sci. 2018;19:3877.

    Article  Google Scholar 

  176. Jiang D, Mu W, Pang X, Liu Y, Zhang N, Song Y, et al. Cascade cytosol delivery of dual-sensitive micelle-tailored vaccine for enhancing cancer immunotherapy. ACS Appl Mater Interfaces. 2018;10:37797–811.

    Article  CAS  Google Scholar 

  177. Garg SM, Vakili MR, Molavi O, Lavasanifar A. Self-associating poly (ethylene oxide)-block-poly (α-carboxyl-ε-caprolactone) drug conjugates for the delivery of STAT3 inhibitor JSI-124: potential application in cancer immunotherapy. Mol Pharm. 2017;14:2570–84.

    Article  CAS  Google Scholar 

  178. Wang X, Li M, Ren K, Xia C, Li J, Yu Q, et al. On-demand autophagy cascade amplification nanoparticles precisely enhanced oxaliplatin-induced cancer immunotherapy. Adv Mater. 2020;32:2002160.

    Article  CAS  Google Scholar 

  179. Yuba E, Sakaguchi N, Kanda Y, Miyazaki M, Koiwai K. pH-responsive micelle-based cytoplasmic delivery system for induction of cellular immunity. Vaccines. 2017;5:41.

    Article  Google Scholar 

  180. Peng J, Xiao Y, Li W, Yang Q, Tan L, Jia Y, et al. Photosensitizer micelles together with IDO inhibitor enhance cancer photothermal therapy and immunotherapy. Adv Sci. 2018;5:1700891.

    Article  Google Scholar 

  181. Li H, Li Y, Wang X, Hou Y, Hong X, Gong T, et al. Rational design of polymeric hybrid micelles to overcome lymphatic and intracellular delivery barriers in cancer immunotherapy. Theranostics. 2017;7:4383.

    Article  CAS  Google Scholar 

  182. Jani D, Allinson J, Berisha F, Cowan KJ, Devanarayan V, Gleason C, et al. Recommendations for use and fit-for-purpose validation of biomarker multiplex ligand binding assays in drug development. AAPS J. 2016;18:1–14.

    Article  CAS  Google Scholar 

  183. Bobo D, Robinson KJ, Islam J, Thurecht KJ, Corrie SR. Nanoparticle-based medicines: a review of FDA-approved materials and clinical trials to date. Pharm Res. 2016;33:2373–87.

    Article  CAS  Google Scholar 

  184. Wu L, Zou Y, Deng C, Cheng R, Meng F, Zhong Z. Intracellular release of doxorubicin from core-crosslinked polypeptide micelles triggered by both pH and reduction conditions. Biomaterials. 2013;34:5262–72.

    Article  CAS  Google Scholar 

  185. Sang X, Yang Q, Shi G, Zhang L, Wang D, Ni C. Preparation of pH/redox dual responsive polymeric micelles with enhanced stability and drug controlled release. Mater Sci Eng C. 2018;91:727–33.

    Article  CAS  Google Scholar 

  186. Li B, Pang S, Li X, Li Y. PH and redox dual-responsive polymeric micelles with charge conversion for paclitaxel delivery. J Biomater Sci Polym Ed. 2020;31:2078–93.

    Article  CAS  Google Scholar 

  187. Yang Z, Cheng R, Zhao C, Sun N, Luo H, Chen Y, et al. Thermo-and pH-dual responsive polymeric micelles with upper critical solution temperature behavior for photoacoustic imaging-guided synergistic chemo-photothermal therapy against subcutaneous and metastatic breast tumors. Theranostics. 2018;8:4097.

    Article  CAS  Google Scholar 

  188. Liu H, Wang K, Yang C, Huang S, Wang M. Multifunctional polymeric micelles loaded with doxorubicin and poly (dithienyl-diketopyrrolopyrrole) for near-infrared light-controlled chemo-phototherapy of cancer cells. Colloids Surf B. 2017;157:398–406.

    Article  CAS  Google Scholar 

  189. Song L, Zhang B, Jin E, Xiao C, Li G, Chen X. A reduction-sensitive thermo-responsive polymer: Synthesis, characterization, and application in controlled drug release. Eur Polymer J. 2018;101:183–9.

    Article  CAS  Google Scholar 

  190. Liu X, Li C, Lv J, Huang F, An Y, Shi L, et al. Glucose and h2o2 dual-responsive polymeric micelles for the self-regulated release of insulin. ACS Appl Bio Mater. 2020;3:1598–606.

    Article  CAS  Google Scholar 

  191. Huang Y, Tang Z, Peng S, Zhang J, Wang W, Wang Q, et al. pH/redox/UV irradiation multi-stimuli responsive nanogels from star copolymer micelles and Fe3+ complexation for “on-demand” anticancer drug delivery. React Funct Polym. 2020;149: 104532.

    Article  CAS  Google Scholar 

  192. Qu J, Wang QY, Kl Chen, Luo JB, Zhou QH, Lin J. Reduction/temperature/pH multi-stimuli responsive core cross-linked polypeptide hybrid micelles for triggered and intracellular drug release. Colloids Surf B Biointerfaces. 2018;170:373–81.

    Article  CAS  Google Scholar 

  193. Dong Y, Ma X, Huo H, Zhang Q, Qu F, Chen F. Preparation of quadruple responsive polymeric micelles combining temperature-, pH-, redox-, and UV-responsive behaviors and its application in controlled release system. J Appl Polym Sci. 2018;135:46675.

    Article  Google Scholar 

  194. Zhang D, Li J, Xie H, Zhu A, Xu Y, Zeng B, et al. Polyion complex micelles formed by azobenzene-based polymer with multi-responsive properties. J Appl Polym Sci. 2021;138:50580.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors are grateful to the entire administration of AUUP, Noida, India, for their unwavering support in completing the aforementioned work.

Author information

Authors and Affiliations

  1. Amity Institute of Microbial Technology, Amity University Uttar Pradesh, Noida, Uttar Pradesh, 201303, India

    Sharath Kumar Hari, Ankita Gauba & Neeraj Shrivastava

  2. Amity Institute of Nanotechnology, Amity University Uttar Pradesh, Noida, Uttar Pradesh, 201303, India

    Ravi Mani Tripathi

  3. School of Studies in Microbiology, Vikram University, Ujjain, Madhya Pradesh, 456010, India

    Sudhir Kumar Jain

  4. Department of Biological Sciences, Rani Durgavati University, Jabalpur, M.P, 482001, India

    Akhilesh Kumar Pandey

  5. Vikram University, Ujjain, Madhya Pradesh, 456010, India

    Akhilesh Kumar Pandey

Authors
  1. Sharath Kumar Hari
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ankita Gauba
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Neeraj Shrivastava
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ravi Mani Tripathi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sudhir Kumar Jain
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Akhilesh Kumar Pandey
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the study conception and design. R.M. Tripathi, N. Shrivastava, S. K. Jain, and A.K. Pandey planned and structured the review. Material preparation, data collection, analysis, preparation of the first draft, and all the illustrations were created by Ankita Gauba and Sharath Kumar Hari. All authors commented on previous versions of the manuscript. Supervision was done by R.M. Tripathi, N. Shrivastava, S. K. Jain, and A.K. Pandey. All the authors critically revised the work and approved the final version.

Corresponding author

Correspondence to Ravi Mani Tripathi.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

We agreed with the journal policy and provided our consent for the publication.

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Sharath Kumar Hari and Ankita Gauba have equal contribution.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hari, S.K., Gauba, A., Shrivastava, N. et al. Polymeric micelles and cancer therapy: an ingenious multimodal tumor-targeted drug delivery system. Drug Deliv. and Transl. Res. 13, 135–163 (2023). https://doi.org/10.1007/s13346-022-01197-4

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13346-022-01197-4

Keywords

Search

Navigation