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A novel pH-and temperature sensitive polymer based on MoS2 modified poly (N-Isopropyl Acrylamide)/ allyl acetoacetate for doxorubicin delivery: synthesis, characterization, in-vitro release and cytotoxicity studies

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Abstract

In this paper, we aimed to develop the nanocarrier based on poly (N-isopropyl acrylamide)—allyl acetoacetate grafted MoS2 nanosheets. The obtained polymer modified with methoxy poly (ethylene glycol) and folic acid to enable enhanced adsorption of doxorubicin. The synthesized polymer was characterized using Fourier transform infrared, X-ray diffraction, field emission scanning electron microscope, and thermogravimetric analysis. The effect of main experimental parameters on the doxorubicin adsorption were investigated and the maximum adsorption capacity was obtained at pH = 8, contact time = 15 min, and temperature = 50 °C. The results indicated that the doxorubicin release was considerably accelerated at a simulated cancer fluids (pH = 5.6) in contrast to simulated human blood fluids (pH = 7.4). Also, the cytotoxicity of the obtained nanocarrier was evaluated via MTT assay against KB cancer cell lines. The doxorubicin release and subsequent induction of apoptosis enhanced after near infrared irradiation, indicating that this nanocarrier can be employed as a dual responsive drug delivery system, with controlled drug release through near infrared irradiation and pH. The adsorption data followed the Langmuir isotherm model with a maximum adsorption capacity of 16.83 mg g−1. Kinetic studies revealed that the adsorption process was fitted with the pseudo-second-order model.

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Abbreviations

DOX:

Doxorubicin

DDSs:

Drug delivery systems

PTT:

Photothermal therapy

NIR:

Near infrared

MoS2 :

Molybdenum disulfide

TMDCs:

Transition- metal di-chalcogenides

pNIPAm:

Poly (N-isopropylacrylamide)

PEG:

Poly (ethylene glycol)

MPEG:

Methoxy poly (ethylene glycol)

FA:

Folic acid

FR:

Folic acid receptors

ABIN:

2,2, Azobisisobutyronitrile

DMF:

Dimethylformamide

AAA:

Allyl acetoacetate

DI:

Deionized

FTIR:

Fourier transform infrared

XRD:

X-ray diffraction

FE-SEM:

Field emission scanning electron microscope

EDX:

Energy-dispersive X-ray analysis

TGA:

Thermogravimetric analysis: TGA;

ICP-MS:

Inductively coupled plasma-mass spectrometry: ICP-MS

PBS:

Phosphate-buffered saline

DMEM:

Dulbecco’s modified Eagle’s medium

DMSO:

Fetal bovine serum: FBS; Dimethyl sulfoxide

OD:

Optical density

References

  1. Fu F, Wu Y, Zhu J, Wen S, Shen M, Shi X (2014) Multifunctional lactobionic acid-modified dendrimers for targeted drug delivery to liver cancer cells: investigating the role played by PEG spacer. ACS Appl Mater Interfaces 6:16416–16425

    Article  CAS  PubMed  Google Scholar 

  2. Huang YS, Lu YJ, Chen JP (2017) Magnetic graphene oxide as a carrier for targeted delivery of chemotherapy drugs in cancer therapy. J Magn Magn Mater 427:34–40

    Article  CAS  Google Scholar 

  3. Karimi S, Namazi H (2020) Simple preparation of maltose-functionalized dendrimer/graphene quantum dots as a pH-sensitive biocompatible carrier for targeted delivery of doxorubicin. Int J Biol Macromol 156:648–659

    Article  CAS  PubMed  Google Scholar 

  4. Shi W, Ching YC, Chuah CH (2021) Preparation of aerogel beads and microspheres based on chitosan and cellulose for drug delivery: A review. Int J Biol Macromol 170:751–767

    Article  CAS  PubMed  Google Scholar 

  5. Ghezzi M, Pescina S, Padula C, Santi P, Del Favero E, Cantù L, Nicoli S (2021) Polymeric micelles in drug delivery: An insight of the techniques for their characterization and assessment in biorelevant conditions. J Control Release 332:312–336

    Article  CAS  PubMed  Google Scholar 

  6. Padash Hooshyar S, Mehrabian RZ, Ahmad Panahi H, Jouybari MH, Jalilian H (2019) Synthesis and characterization of magnetized-PEGylated dendrimer anchored to thermosensitive polymer for letrozole drug delivery. Colloids Surf B 176:404–411

    Article  Google Scholar 

  7. Torabi Fard N, Tadayon F, Ahmad Panahi H, Moniri E (2022) The synthesis of functionalized graphene oxide by polyester dendrimer as a pH-sensitive nanocarrier for targeted delivery of venlafaxine hydrochloride: Central composite design optimization. J Mol Liq 349:118149

    Article  CAS  Google Scholar 

  8. Large DE, Abdelmessih RG, Fink EA, Auguste DT (2021) Liposome composition in drug delivery design, synthesis, characterization, and clinical application. Adv Drug Deliv Rev 176:113851

    Article  CAS  PubMed  Google Scholar 

  9. Abniki M, Azizi Z, Ahmad Panahi H (2021) Design of 3-aminophenol-grafted polymer-modified zinc sulphide nanoparticles as drug delivery system. IET Nanobiotechnol 15:664–673

    Article  PubMed  PubMed Central  Google Scholar 

  10. Kaveh S, Tazikeh-Lemeski E, Moniri E, Ahmad Panahi H, Beiknejad D (2021) Preparation and characterization of dendrimer-modified graphene oxide nanoparticles for loading and releasing of doxorubicin. Fuller Nanotub 29:540–546

    Article  CAS  Google Scholar 

  11. Parham N, Panahi HA, Feizbakhsh A, Moniri E (2020) Synthesis of PEGylated superparamagnetic dendrimers and their applications as a drug delivery system. Polym Adv Technol 32:1568–1578

    Article  Google Scholar 

  12. Zou L, Wang H, He B, Li Z, Tan T, Cao H, He H, Zhang Z, Guo S, Li Y (2016) Current approaches of photothermal therapy in treating cancer metastasis with nanotherapeutics. Theranostics 6:762

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Yang K, Yang G, Chen L, Cheng L, Wang L, Ge C, Liu Z (2015) FeS nanoplates as a multifunctional nano-theranostic for magnetic resonance imaging guided photothermal therapy. Biomaterials 38:1–9

    Article  PubMed  Google Scholar 

  14. Chen Z, Wang Q, Wang H, Zhang L, Song G, Song G, Hu J, Wang H, Liu J, Dongyuan Zhao M (2013) Ultrathin PEGylated W18O49 nanowires as a new 980 nm-laser-driven photothermal agent for efficient ablation of cancer cells in vivo. Adv Mater 25:2095–2100

    Article  CAS  PubMed  Google Scholar 

  15. Jaque D, Maestro LM, Del Rosal B, Haro-Gonzalez P, Benayas A, Plaza JL, Martín Rodríguez E, García Solé J (2014) Nanoparticles for photothermal therapies nanoscale 6:9530

    Google Scholar 

  16. Wang K, Chen Q, Xue W, Li S, Liu Z (2017) Combined chemo-photothermal antitumor therapy using molybdenum disulfide modified with hyperbranched polyglycidyl. ACS Biomater Sci Eng 3:2325–2335

    Article  CAS  PubMed  Google Scholar 

  17. Vines JB, Yoon JH, Ryu NU, Lim DJ, Park H (2019) Gold nanoparticles for photothermal cancer therapy. Front Chem 7:167

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Moon HK, Lee SH, Choi HC (2009) In vivo near-infrared mediated tumor destruction by photothermal effect of carbon nanotubes. ACS Nano 3:3707–3713

    Article  CAS  PubMed  Google Scholar 

  19. Chang X, Zhang M, Wang C, Zhang J, Wu H, Yang S (2020) Graphene oxide/BaHoF5/PEG nanocomposite for dual-modal imaging and heat shock protein inhibitor-sensitized tumor photothermal therapy. Carbon 158:372–385

    Article  CAS  Google Scholar 

  20. Tian Q, Hu J, Zhu Y, Zou R, Chen Z, Yang S, Li R, Su Q, Han Y, Liu X (2013) Sub-10 nm Fe3O4@ Cu2–x Score–shell nanoparticles for dual-modal imaging and photothermal therapy. J Am Chem Soc 135:8571–8577

    Article  CAS  PubMed  Google Scholar 

  21. Chou SS, Kaehr B, Kim J, Foley BM, De M, Hopkins PE, Huang J, Brinker CJ, Dravid VP (2013) Chemically exfoliated MoS2 as near-infrared photothermal agents. Angew Chem Int Ed 52:4160–4164

    Article  CAS  Google Scholar 

  22. Wang X, Wang X, Cheng S, Ye M, Zhang C, Xian Y (2020) Near-Infrared Light-Switched MoS2 Nanoflakes@ Gelatin Bioplatform for Capture, Detection, and Nondestructive Release of Circulating Tumor Cells. Anal Chem 92:3111–3117

    Article  CAS  PubMed  Google Scholar 

  23. Liu L, Jiang H, Dong J, Zhang W, Dang G, Yang M, Li Y, Chen H, Ji H, Dong L (2020) PEGylated MoS2 quantum dots for traceable and pH-responsive chemotherapeutic drug delivery. Colloids Surf B 185:110590

    Article  CAS  Google Scholar 

  24. Li Z, Yang Y, Yao J, Shao Z, Chen X (2020) A facile fabrication of silk/ MoS2 hybrids for Photothermal therapy. Mater Sci Eng C 79:123–129

    Article  Google Scholar 

  25. Khafaji M, Zamani M, Golizadeh M, Bavi O (2019) Inorganic nanomaterials for chemo/photothermal therapy: a promising horizon on effective cancer treatment. Biophys Rev 11:335–352

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Khodabakhshi MJ, Ahmad Panahi H, Konoz E, Feizbakhsh A, Kimiagar S (2020) Synthesis of pH and thermo‐sensitive dendrimers based on MoS2 and magnetic nanoparticles for cisplatin drug delivery system by the near‐infrared laser. Polym Adv Technol

  27. Khodabakhshi MJ, Ahmad Panahi H, Konoz E, Feizbakhsh A, Kimiagar S (2021) NIR- triggered drug delivery system based on Fe3O4- MoS2 core-shell grafted poly (N- vinylcaprolactam): isotherm and kinetics studies. Polym-Plast Tech Mat 1247–1260

  28. Yang Y, Wu J, Bremner DH, Niu S, Li Y, Zhang XJ, Xie X, Zhu LM (2020) A multifunctional nanoplatform based on MoS2 -nanosheets for targeted drug delivery and chemo-photothermal therapy. Colloids Surf B 185:110585

    Article  CAS  Google Scholar 

  29. Kim J, Kim H, Kim WJ (2016) Single-layered MoS2 –PEI–PEG nanocomposite-mediated gene delivery controlled by photo and redox stimuli. Small 12:1184–1192

    Article  CAS  PubMed  Google Scholar 

  30. Kukkar M, Tuteja SK, Kumar P, Kim KH, Bhadwal AS, Deep A (2018) A novel approach for amine derivatization of MoS2 nanosheets and their application toward label-free immunosensor. Anal Biochem 555:1–8

    Article  CAS  PubMed  Google Scholar 

  31. Chen L, Xu J, Wang Y, Huang R (2021) Ultra-small MoS2 nanodots-incorporated mesoporous silica nanospheres for pH-sensitive drug delivery and CT imaging. J Mater Sci Technol 63:91–96

    Article  CAS  Google Scholar 

  32. Zeng G, Chen T, Huang L, Meiying L, Ruming J, Qing W, Yanfeng D, Yuanqing W, Xiaoyong Z, Yen W (2018) Surface modification and drug delivery applications of MoS2 nanosheets with polymers through the combination of mussel inspired chemistry and SET-LRP. J Taiwan Inst Chem Eng 82:205–213

    Article  CAS  Google Scholar 

  33. Almeida H, Helena Amaral M, Lobão P (2012) Temperature and pH stimuli-responsive polymers and their applications in controlled and selfregulated drug delivery. J App Pharm Sci 2:1–10

    CAS  Google Scholar 

  34. Macewan SR, Callahan DJ, Chilkoti A (2010) Stimulus-responsive macromulecules and nanoparticules for cancer drug delivery. Nanomedicine UK 5:793–806

    Article  CAS  Google Scholar 

  35. Gil ES, Hudson SM (2004) Stimuli-responsive polymers and their bioconjugates. Prog Polym Sci 29:1173–1222

    Article  CAS  Google Scholar 

  36. Khalaj Moazen M, Ahmad Panahi H (2017) Magnetic iron oxide nanoparticles grafted N-isopropylacrylamide/chitosan copolymer for the extraction and determination of letrozole in human biological samples. J Sep Sci 40:1125–1132

    Article  CAS  PubMed  Google Scholar 

  37. Khodabakhshi MJ, Ahmad Panahi H, Konoz E, Feizbakhsh A, Kimiagar S (2021) Synthesis of pH and thermo-sensitive dendrimers based on MoS2 and magnetic nanoparticles for cisplatin drug delivery system by the near-infrared laser. Polym Adv Technol 32:1626–1635

    Article  CAS  Google Scholar 

  38. Ashuri A, Miralinaghi M, Moniri E (2022) Evaluation of folic acid-conjugated chitosan grafted Fe3O4/graphene oxide as a pH- and magnetic field-responsive system for adsorption and controlled release of gemcitabine. Korean J Chem Eng 39:1880–1890

    Article  CAS  Google Scholar 

  39. Le Thuy Trang N, Tien Dung Nguyen D, Hoi Nguyen N, Khoa Nguyen C, Dai D, Nguyen H (2021) Methoxy polyethylene glycol–cholesterol modified soy lecithin liposomes for poorly water-soluble anticancer drug delivery. J Appl Polym Sci 138:49858

    Article  Google Scholar 

  40. Gebrie HT, Addisu KD, Darge HF, Worku Mekonnen T, Thankachan kottackal D, Tsai H.C, (2021) Development of thermo/redox-responsive diselenide linked methoxy poly (ethylene glycol)-block-poly (ε-caprolactone-co-p-dioxanone) hydrogel for localized control drug release. J Polym Res 28:448

    Article  CAS  Google Scholar 

  41. Shen H, Liu Q, Liu D, Yu S, Wang X, Yang M (2021) Fabrication of doxorubicin conjugated methoxy poly(ethylene glycol)-block-poly(ε-caprolactone) nanoparticles and study on their in vitro antitumor activities. J Biomater Sci Polym Ed 32:1703–1717

    Article  CAS  PubMed  Google Scholar 

  42. Cheng W, Nie J, Xu L, Liang C, Peng Y, Liu G, Wang T, Mei L, Huang L, Zeng X (2017) pH- sensitive delivery vehicle based on folic acid-conjugated polydopamine-modified mesoporous silica nanoparticles for targeted cancer therapy. ACS Appl Mater Interfaces 9:18462–18473

    Article  CAS  PubMed  Google Scholar 

  43. Jahan ST, Sadat S, Walliser M, Haddadi A (2017) Targeted therapeutic nanoparticles: an immense promise to fight against cancer. J Drug Deliv

  44. Jiao Z, Wang X, Chen Z (2011) Folate-conjugated methoxy poly (ethylene glycol)/poly (L-Alanine) amphiphilic block copolymeric micelles for targeted delivery of paclitaxel. Drug Deliv 18:478–484

    Article  CAS  PubMed  Google Scholar 

  45. Agabeigi R, Rasta S, Rahmati-Yamchi M, Salehi R, Alizadeh E (2020) Novel Chemo-Photothermal Therapy in Breast Cancer Using Methotrexate-Loaded Folic Acid Conjugated Au@ SiO2 Nanoparticles. Nanoscale Res Lett 15:1–14

    Article  Google Scholar 

  46. Hamrang R, Moniri E, Heydarinasab A, Safaeijavan R (2022) In vitro evaluation of copper sulfide nanoparticles decorated with folic acid/chitosan as a novel pH-sensitive nanocarrier for the efficient controlled targeted delivery of cytarabine as an anticancer drug. Biotechnol Appl Biochem

  47. Wang S, Li K, Chen Y, Chen H, Ma M, Feng J, Zhao Q, Shi J (2015) Biocompatible PEGylated MoS2 nanosheets: controllable bottom-up synthesis and highly efficient photothermal regression of tumor. Biomaterials 39:206–217. https://doi.org/10.1016/j.biomaterials.2014.11.009

  48. Shen P, Li Q, Zhang H, Liu R, Liu B, Yang X, Dong Q, Cui T, Liu B (2017) Raman and IR spectroscopic characterization of molybdenum disulfide under quasi-hydrostatic and non-hydrostatic conditions. physica. Status Solidi 254:1600798

  49. Reza Soltani E, Tahvildari K, Moniri E, Ahmad PH (2021) NIR-Laser Triggered Drug Release from Molybdenum Disulfide Nanosheets Modified with Thermosensitive Polymer for Prostate Cancer Treatment. J Inorg Organomet Polym Mater 31:4659–4669

    Article  CAS  Google Scholar 

  50. Zhang D, Fan X, Yang A, Zong X (2018) Hierarchical assembly of urchin-like alpha-iron oxide hollow microspheres and molybdenum disulphide nanosheets for ethanol gas sensing. J Colloid Interface Sci 523:217–225

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Acknowledgements

The authors would like to acknowledge Islamic Azad University (North Tehran Branch) for financial support of this project.

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The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

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Contributions

Elham Reza Soltani: Methodology, Conceptualization, Investigation, Formal analysis, Validation, Writing-original draft. Kambiz Tahvildari: Supervision, Project administration, Formal analysis, Validation, Writing-original draft. Elham Moniri: Supervision, Project administration, Formal analysis, Validation, Writing-original draft. Homayon Ahmad Panahi: Project administration, Formal analysis, Writing-review and editing, Investigation.

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Correspondence to Kambiz Tahvildari or Elham Moniri.

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Reza Soltani, E., Tahvildari, K., Moniri, E. et al. A novel pH-and temperature sensitive polymer based on MoS2 modified poly (N-Isopropyl Acrylamide)/ allyl acetoacetate for doxorubicin delivery: synthesis, characterization, in-vitro release and cytotoxicity studies. J Polym Res 29, 446 (2022). https://doi.org/10.1007/s10965-022-03286-x

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