Skip to main content

Advertisement

SpringerLink
Log in

Recent progress of macrophage vesicle-based drug delivery systems

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

Abstract

Nanoparticle drug delivery systems (NDDSs) are promising platforms for efficient delivery of drugs. In the past decades, many nanomedicines have received clinical approval and completed translation. With the rapid advance of nanobiotechnology, natural vectors are emerging as novel strategies to carry and delivery nanoparticles and drugs for biomedical applications. Among diverse types of cells, macrophage is of great interest for their essential roles in inflammatory and immune responses. Macrophage-derived vesicles (MVs), including exosomes, microvesicles, and those from reconstructed membranes, may inherit the chemotactic migration ability and high biocompatibility. The unique properties of MVs make them competing candidates as novel drug delivery systems for precision nanomedicine. In this review, the advantages and disadvantages of existing NDDSs and MV-based drug delivery systems (MVDDSs) were compared. Then, we summarized the potential applications of MVDDSs and discuss future perspectives. The development of MVDDS may provide avenues for the treatment of diseases involving an inflammatory process.

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

Similar content being viewed by others

Availability of data and materials

Not applicable.

Abbreviations

AA-PEG:

Aminoethylanisamide-polyethylene glycol

BDNF:

Brain-derived neurotrophic factor

BNCT:

Boron neutron capture therapy

CCR2:

C-C chemokine receptor type 2

DEX:

Dexamethasone sodium phosphate

DOX:

Adriamycin

EV:

Extracellular vesicles

MM:

Macrophage membrane

MPS:

Mononuclear phagocytic system

MVDDS:

Macrophage vesicle-based drug delivery system

NP:

Nanoparticle

PLGA:

Poly(lactic-co-glycolic acid)

PTX:

Paclitaxel

RGE:

Neuropilin-1-targeted peptide

RMM:

Reconstructed macrophage membrane

RVG29:

Rabies virus glycoprotein

ROS:

Reactive oxygen species

SPION:

Superparamagnetic iron oxide nanoparticles

TLR4:

Toll-like receptor 4

TPP:

Triphenylphosphine cation

References

  1. Florea A-M, Busselberg D. Cisplatin as an anti-tumor drug: cellular mechanisms of activity, drug resistance and induced side effects. Cancers. 2011;3(1): 1351–71.

  2. de Jong WH, Borm PJA. Drug delivery and nanoparticles: applications and hazards. Int J Nanomed. 2008;3(2):133–49.

    Article  Google Scholar 

  3. Dai Y, Xu C, Sun X, et al. Nanoparticle design strategies for enhanced anticancer therapy by exploiting the tumour microenvironment. Chem Soc Rev. 2017;46(12):3830–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Kalyane D, Raval N, Maheshwari R, et al. Employment of enhanced permeability and retention effect (EPR): nanoparticle-based precision tools for targeting of therapeutic and diagnostic agent in cancer. Mater Sci Eng C-Mater Biol Appl. 2019;98:1252–76.

    Article  CAS  Google Scholar 

  5. Oberli MA, Reichmuth AM, Dorkin JR, et al. Lipid nanoparticle assisted mRNA delivery for potent cancer immunotherapy. Nano Lett. 2017;17(3):1326–35.

    Article  CAS  PubMed  Google Scholar 

  6. McNamara K, Tofail SAM. Nanoparticles in biomedical applications. Adv Phys-X. 2017;2(1):54–88.

    CAS  Google Scholar 

  7. Peer D, Karp JM, Hong S, et al. Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol. 2007;2(12):751–60.

    Article  CAS  PubMed  Google Scholar 

  8. Fang J, Nakamura H, Maeda H. The EPR effect: unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect. Adv Drug Deliv Rev. 2011;63(3):136–51.

    Article  CAS  PubMed  Google Scholar 

  9. Anselmo AC, Mitragotri S. Nanoparticles in the clinic: an update. Bioeng Transl Med. 2019;4(3).

  10. Caracciolo G. Clinically approved liposomal nanomedicines: lessons learned from the biomolecular corona. Nanoscale. 2018;10(9):4167–72.

    Article  CAS  PubMed  Google Scholar 

  11. Bulbake U, Doppalapudi S, Kommineni N, et al. Liposomal formulations in clinical use: an updated review. Pharmaceutics. 2017;9(2).

  12. Janeway CA, Medzhitov R. Innate immune recognition. Annu Rev Immunol. 2002;20:197–216.

    Article  CAS  PubMed  Google Scholar 

  13. Fang RH, Kroll AV, Gao W, et al. Cell membrane coating nanotechnology. Adv Mater. 2018;30(23).

  14. Chen Z, Wen D, Gu Z. Cargo-encapsulated cells for drug delivery. Science China-Life Sciences. 2020;63(4):599–601.

    Article  PubMed  Google Scholar 

  15. Samuelsson B. Leukotrienes: mediators of immediate hypersensitivity reactions and inflammation. Science (New York, NY). 1983;220(4597):568–75.

    Article  CAS  Google Scholar 

  16. Ley K, Laudanna C, Cybulsky MI, et al. Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol. 2007;7(9):678–89.

    Article  CAS  PubMed  Google Scholar 

  17. Schaffner T, Keller HU, Hess MW, et al. Macrophage functions in antimicrobial defense. Klin Wochenschr. 1982;60(14):720–6.

    Article  CAS  PubMed  Google Scholar 

  18. Anderson NR, Minutolo NG, Gill S, et al. Macrophage-based approaches for cancer immunotherapy. Can Res. 2021;81(5):1201–8.

    Article  CAS  Google Scholar 

  19. Vitale I, Manic G, Coussens LM, et al. Macrophages and metabolism in the tumor microenvironment. Cell Metab. 2019;30(1):36–50.

    Article  CAS  PubMed  Google Scholar 

  20. Clark RA, Stone RD, Leung DY, et al. Role of macrophages in would healing. Surgical forum. 1976;27(62):16–8.

    CAS  PubMed  Google Scholar 

  21. Smigiel KS, Parks WC. Macrophages, wound healing, and fibrosis: recent insights. Curr Rheumatol Rep. 2018;20(4).

  22. Mosser DM, Edwards JP. Exploring the full spectrum of macrophage activation. Nat Rev Immunol. 2008;8(12):958–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Goulielmaki E, Ioannidou A, Tsekrekou M, et al. Tissue-infiltrating macrophages mediate an exosome-based metabolic reprogramming upon DNA damage. Nat Commun. 2020;11(1).

  24. Lan J, Sun L, Xu F, et al. M2 macrophage-derived exosomes promote cell migration and invasion in colon cancer. Can Res. 2019;79(1):146–58.

    Article  CAS  Google Scholar 

  25. Nguyen M-A, Karunakaran D, Geoffrion M, et al. Extracellular vesicles secreted by atherogenic macrophages transfer MicroRNA to inhibit cell migration. Arterioscler Thromb Vas Biol. 2018, 38(1): 49–63.

  26. Zhu X, Shen H, Yin X, et al. Macrophages derived exosomes deliver miR-223 to epithelial ovarian cancer cells to elicit a chemoresistant phenotype. J Exp Clin Cancer Res. 2019;38.

  27. Shao J, Li S, Liu Y, et al. Extracellular vesicles participate in macrophage-involved immune responses under liver diseases. Life Sci. 2020;240.

  28. Vlassov AV, Magdaleno S, Setterquist R, et al. Exosomes: current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. BBA-Gen Subjects. 2012;1820(7):940–8.

    Article  CAS  Google Scholar 

  29. Xu R, Greening DW, Zhu H-J, et al. Extracellular vesicle isolation and characterization: toward clinical application. J Clin Investig. 2016;126(4): 1152–62.

  30. Kalluri R, Lebleu VS. The biology, function, and biomedical applications of exosomes. Science. 2020;367(6478): 640-+.

  31. Hessvik NP, Llorente A. Current knowledge on exosome biogenesis and release. Cell Mol Life Sci. 2018;75(2):193–208.

    Article  CAS  PubMed  Google Scholar 

  32. Wu P, Zhang B, Ocansey DKW, et al. Extracellular vesicles: a bright star of nanomedicine. Biomaterials. 2021;269: 120467.

  33. Bang C, Thum T. Exosomes: New players in cell-cell communication. Int J Biochem Cell Biol. 2012;44(11):2060–4.

    Article  CAS  PubMed  Google Scholar 

  34. Kanchanapally R, Deshmukh SK, Chavva SR, et al. Drug-loaded exosomal preparations from different cell types exhibit distinctive loading capability, yield, and antitumor efficacies: a comparative analysis. Int J Nanomed. 2019;14:531–41.

    Article  CAS  Google Scholar 

  35. Khan I, Saeed K, Khan I. Nanoparticles: Properties, applications and toxicities. Arab J Chem. 2019;12(7):908–31.

    Article  CAS  Google Scholar 

  36. Patra JK, Das G, Fraceto LF, et al. Nano based drug delivery systems: recent developments and future prospects. J Nanobiotechnol. 2018;16.

  37. Shi J, Kantoff PW, Wooster R, et al. Cancer nanomedicine: progress, challenges and opportunities. Nat Rev Cancer. 2017;17(1):20–37.

    Article  CAS  PubMed  Google Scholar 

  38. Zhang L, Beatty A, Lu L, et al. Microfluidic-assisted polymer-protein assembly to fabricate homogeneous functionalnanoparticles. Mater Sci Eng C-Mater Biol Appl. 2020;111.

  39. Strand MS, Krasnick BA, Pan H, et al. Precision delivery of RAS-inhibiting siRNA to KRAS driven cancer via peptide-based nanoparticles. Oncotarget. 2019;10(46):4761–75.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Seo Y-E, Suh H-W, Bahal R, et al. Nanoparticle-mediated intratumoral inhibition of miR-21 for improved survival in glioblastoma. Biomaterials. 2019;201: 87–98.

  41. Petersen GH, Alzghari SK, Chee W, et al. Meta-analysis of clinical and preclinical studies comparing the anticancer efficacy of liposomal versus conventional non-liposomal doxorubicin. J Control Release. 2016;232:255–64.

    Article  CAS  PubMed  Google Scholar 

  42. Mitchell MJ, Billingsley MM, Haley RM, et al. Engineering precision nanoparticles for drug delivery. Nat Rev Drug Discovery. 2021;20(2):101–24.

    Article  CAS  PubMed  Google Scholar 

  43. Anselmo AC, Mitragotri S. Impact of particle elasticity on particle-based drug delivery systems. Adv Drug Deliv Rev. 2017;108:51–67.

    Article  CAS  PubMed  Google Scholar 

  44. Mohammed L, Gomaa HG, Ragab D, et al. Magnetic nanoparticles for environmental and biomedical applications: a review. Particuology. 2017;30:1–14.

    Article  CAS  Google Scholar 

  45. Dalzon B, Guidetti M, Testemale D, et al. Utility of macrophages in an antitumor strategy based on the vectorization of iron oxide nanoparticles. Nanoscale. 2019;11(19):9341–52.

    Article  CAS  PubMed  Google Scholar 

  46. Yang H, Shao R, Huang H, et al. Engineering macrophages to phagocytose cancer cells by blocking the CD47/SIRPα axis. Cancer Med. 2019;8(9):4245–53.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Liu X, Li H, Chen Y, et al. Mixed-charge nanoparticles for long circulation, low reticuloendothelial system clearance, and high tumor accumulation. Adv Healthcare Mater. 2014;3(9):1439–47.

    Article  CAS  Google Scholar 

  48. Owens DE, Peppas NA. Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int J Pharm. 2006;307(1):93–102.

    Article  CAS  PubMed  Google Scholar 

  49. Suk JS, Xu QG, Kim N, et al. PEGylation as a strategy for improving nanoparticle-based drug and gene delivery. Adv Drug Deliv Rev. 2016;99:28–51.

    Article  CAS  PubMed  Google Scholar 

  50. Abuchowski A, McCoy JR, Palczuk NC, et al. Effect of covalent attachment of polyethylene glycol on immunogenicity and circulating life of bovine liver catalase. J Biol Chem. 1977;252(11):3582–6.

    Article  CAS  PubMed  Google Scholar 

  51. Elahi N, Kamali M, Baghersad MH. Recent biomedical applications of gold nanoparticles: a review. Talanta. 2018;184:537–56.

    Article  CAS  PubMed  Google Scholar 

  52. El-Hammadi MM, Small-Howard AL, Fernandez-Arevalo M, et al. Development of enhanced drug delivery vehicles for three cannabis-based terpenes using poly(lactic-co-glycolic acid) based nanoparticles. Ind Crops Prod. 2021;164.

  53. Rafiei P, Haddadi A. Docetaxel-loaded PLGA and PLGA-PEG nanoparticles for intravenous application: pharmacokinetics and biodistribution profile. Int J Nanomed. 2017;12:935–47.

    Article  CAS  Google Scholar 

  54. Lu J, Liu X, Liao Y-P, et al. Breast cancer chemo-immunotherapy through liposomal delivery of an immunogenic cell death stimulus plus interference in the IDO-1 pathway. Acs Nano. 2018;12(11): 11041–61.

  55. Ishida T, Maeda R, Ichihara M, et al. Accelerated clearance of PEGylated liposomes in rats after repeated injections. J Control Release. 2003;88(1):35–42.

    Article  CAS  PubMed  Google Scholar 

  56. Lubich C, Allacher P, de la Rosa M, et al. The mystery of antibodies against polyethylene glycol (PEG) — what do we know? Pharm Res. 2016;33(9):2239–49.

    Article  CAS  PubMed  Google Scholar 

  57. Batrakova EV, Kim MS. Using exosomes, naturally-equipped nanocarriers, for drug delivery. J Control Release. 2015;219:396–405.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Patel HM. Serum opsonins and liposomes: their interaction and opsonophagocytosis. Crit Rev Ther Drug Carrier Syst. 1992;9(1):39–90.

    CAS  PubMed  Google Scholar 

  59. Liu R, An Y, Jia W, et al. Macrophage-mimic shape changeable nanomedicine retained in tumor for multimodal therapy of breast cancer. J Control Release. 2020;321:589–601.

    Article  CAS  PubMed  Google Scholar 

  60. Zhang Y, Cai K, Li C, et al. Macrophage-membrane-coated nanoparticles for tumor-targeted chemotherapy. Nano Lett. 2018;18(3):1908–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Basel MT, Shrestha TB, Bossmann SH, et al. Cells as delivery vehicles for cancer therapeutics. Ther Deliv. 2014;5(5):555–67.

    Article  CAS  PubMed  Google Scholar 

  62. Li Z, Yu X-F, Chu PK. Recent advances in cell-mediated nanomaterial delivery systems for photothermal therapy. J Mater Chem B. 2018;6(9): 1296–311.

  63. Lee CH, Choi EY. Macrophages and inflammation. J Rheum Dis. 2018;25(1): 11–8.

  64. Sylvestre M, Crane CA, Pun SH. Progress on modulating tumor-associated macrophages with biomaterials. Adv Mater. 2020;32(13).

  65. Wan S-W, Wu-Hsieh BA, Lin Y-S, et al. The monocyte-macrophage-mast cell axis in dengue pathogenesis. J Biomed Sci, 2018;25.

  66. Ross R. Mechanisms of disease — atherosclerosis — an inflammatory disease. N Engl J Med. 1999;340(2):115–26.

    Article  CAS  PubMed  Google Scholar 

  67. Italiani P, Boraschi D. From monocytes to M1/M2 macrophages: phenotypical vs. functional differentiation. Front Immun. 2014;5.

  68. Wynn TA, Chawla A, Pollard JW. Macrophage biology in development, homeostasis and disease. Nature. 2013;496(7446):445–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Thery C, Witwer KW, Aikawa E, et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J Extracellular Vesicles. 2018;7(1).

  70. D'souza-Schorey C, Schorey JS. Regulation and mechanisms of extracellular vesicle biogenesis and secretion [M]//STAHL P, RAPOSO G. Extracellular Vesicles and Mechanisms of Cell-Cell Communication. 2018: 125–33.

  71. van Niel G, D’Angelo G, Raposo G. Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol. 2018;19(4):213–28.

    Article  PubMed  CAS  Google Scholar 

  72. Madsen SJ, Hirschberg H. Macrophages as delivery vehicles for anticancer agents. Ther Deliv. 2019;10(3):189–201.

    Article  CAS  PubMed  Google Scholar 

  73. Guo L, Zhang Y, Wei R, et al. Proinflammatory macrophage-derived microvesicles exhibit tumor tropism dependent on CCL2/CCR2 signaling axis and promote drug delivery via SNARE-mediated membrane fusion. Theranostics. 2020;10(15):6581–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Pang L, Zhu Y, Qin J, et al. Primary M1 macrophages as multifunctional carrier combined with PLGA nanoparticle delivering anticancer drug for efficient glioma therapy. Drug Delivery. 2018;25(1):1922–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Zhang H, Dong S, Li Z, et al. Biointerface engineering nanoplatforms for cancer-targeted drug delivery. Asian J Pharm Sci. 2020;15(4):397–415.

    Article  PubMed  Google Scholar 

  76. Xia Y, Rao L, Yao H, et al. Engineering macrophages for cancer immunotherapy and drug delivery. Adv Mater. 2020;32(40).

  77. Arteaga-Blanco L, Bou-Habib D. The role of extracellular vesicles from human macrophages on host-pathogen interaction. Int J Mol Sci. 2021;22(19).

  78. Marchetti B, Leggio L, L'episcopo F, et al. Glia-derived extracellular vesicles in Parkinson's disease. J Clin Med. 2020;9(6).

  79. Giri P, Schorey J. Exosomes derived from M. bovis BCG infected macrophages activate antigen-specific CD4+ and CD8+ T cells in vitro and in vivo. Plos One. 2008;3(6): e2461.

  80. Robbins P, Morelli A. Regulation of immune responses by extracellular vesicles. Nat Rev Immunol. 2014;14(3):195–208.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Cheng L, Wang Y, Huang L. Exosomes from M1-polarized macrophages potentiate the cancer vaccine by creating a pro-inflammatory microenvironment in the lymph node. Mol Ther. 2017;25(7):1665–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Kim MS, Haney MJ, Zhao Y, et al. Engineering macrophage-derived exosomes for targeted paclitaxel delivery to pulmonary metastases: in vitro and in vivo evaluations. Nanomedicine-Nanotechnology Biology and Medicine. 2018;14(1):195–204.

    Article  CAS  PubMed  Google Scholar 

  83. Tang T-T, Lv L-L, Wang B, et al. Employing macrophage-derived microvesicle for kidney-targeted delivery of dexamethasone: an efficient therapeutic strategy against renal inflammation and fibrosis. Theranostics. 2019;9(16): 4740–55.

  84. Tang T-T, Lv L-L, Cao J-Y, et al. Employing macrophage-derived microvesicle for kidney-targeted delivery of dexamethasone: an efficient therapeutic strategy against renal inflammation and fibrosis. Nephrol Dial Transplant. 2019;34.

  85. Silva AKA, Luciani N, Gazeau F, et al. Combining magnetic nanoparticles with cell derived microvesicles for drug loading and targeting. Nanomed Nanotech Biol Med. 2015;11(3):645–55.

    Article  CAS  PubMed  Google Scholar 

  86. Sweeney MD, Sagare AP, Zlokovic BV. Blood-brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders. Nat Rev Neurol. 2018;14(3):133–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Dong X. Current strategies for brain drug delivery. Theranostics. 2018;8(6):1481–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Xuan M, Shao J, Dai L, et al. Macrophage cell membrane camouflaged mesoporous silica nanocapsules for in vivo cancer therapy. Adv Healthcare Mater. 2015;4(11):1645–52.

    Article  CAS  Google Scholar 

  89. Yuan D, Zhao Y, Banks WA, et al. Macrophage exosomes as natural nanocarriers for protein delivery to inflamed brain. Biomaterials. 2017;142:1–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Clayton A, Harris CL, Court J, et al. Antigen-presenting cell exosomes are protected from complement-mediated lysis by expression of CD55 and CD59. Eur J Immunol. 2003;33(2):522–31.

    Article  CAS  PubMed  Google Scholar 

  91. Qu Y, Franchi L, Nunez G, et al. Nonclassical IL-1 beta secretion stimulated by P2X7 receptors is dependent on inflammasome activation and correlated with exosome release in murine macrophages. J Immunol. 2007;179(3):1913–25.

    Article  CAS  PubMed  Google Scholar 

  92. Kamerkar S, Lebleu VS, Sugimoto H, et al. Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer. Nature. 2017;546(7659): 498-+.

  93. Yang W, Wang L, Mettenbrink E, et al. Nanoparticle toxicology. Annu Rev Pharmacol Toxicol. 2021;61:269–89.

    Article  CAS  PubMed  Google Scholar 

  94. Rao L, He Z, Meng Q-F, et al. Effective cancer targeting and imaging using macrophage membrane-camouflaged upconversion nanoparticles. J Biomed Mater Res Part A. 2017;105(2): 521–30.

  95. Ji B, Cai H, Yang Y, et al. Hybrid membrane camouflaged copper sulfide nanoparticles for photothermal-chemotherapy of hepatocellular carcinoma. Acta Biomater. 2020;111:363–72.

    Article  CAS  PubMed  Google Scholar 

  96. Wang P, Wang H, Huang Q, et al. Exosomes from M1-polarized macrophages enhance paclitaxel antitumor activity by activating macrophages-mediated inflammation. Theranostics. 2019;9(6):1714–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Doyle LM, Wang MZ. Overview of extracellular vesicles, their origin, composition, purpose, and methods for exosome isolation and analysis. Cells. 2019;8(7).

  98. Moore C, Kosgodage U, Lange S, et al. The emerging role of exosome and microvesicle- (EMV-) based cancer therapeutics and immunotherapy. Int J Cancer. 2017;141(3):428–36.

    Article  CAS  PubMed  Google Scholar 

  99. Haraszti RA, Miller R, Stoppato M, et al. Exosomes produced from 3D cultures of MSCs by tangential flow filtration show higher yield and improved activity. Mol Ther. 2018;26(12):2838–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Christie C, Madsen SJ, Peng Q, et al. Macrophages as nanoparticle delivery vectors for photothermal therapy of brain tumors. Ther Deliv. 2015;6(3):371–84.

    Article  CAS  PubMed  Google Scholar 

  101. Charoenviriyakul C, Takahashi Y, Morishita M, et al. Cell type-specific and common characteristics of exosomes derived from mouse cell lines: yield, physicochemical properties, and pharmacokinetics. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 2017;96:316–22.

    Article  CAS  Google Scholar 

  102. Théry C, Zitvogel L, Amigorena S. Exosomes: composition, biogenesis and function. Nat Rev Immunol. 2002;2(8):569–79.

    Article  PubMed  CAS  Google Scholar 

  103. Parada N, Romero-Trujillo A, Georges N, et al. Camouflage strategies for therapeutic exosomes evasion from phagocytosis. J Adv Res. 2021;31:61–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Jia G, Han Y, An Y, et al. NRP-1 targeted and cargo-loaded exosomes facilitate simultaneous imaging and therapy of glioma in vitro and in vivo. Biomaterials. 2018;178:302–16.

    Article  CAS  PubMed  Google Scholar 

  105. Wang S, Li F, Ye T, et al. Macrophage-tumor chimeric exosomes accumulate in lymph node and tumor to activate the immune response and the tumor microenvironment. Sci Transl Med. 2021;13(615): eabb6981.

  106. Zhang M, Jin K, Gao L, et al. Methods and technologies for exosome isolation and characterization. Small Methods. 2018;2(9):1800021.

    Article  CAS  Google Scholar 

  107. Li P, Kaslan M, Lee SH, et al. Progress in exosome isolation techniques. Theranostics. 2017;7(3):789–804.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Li YJ, Wu JY, Liu J, et al. Artificial exosomes for translational nanomedicine. J Nanobiotechnology. 2021;19(1):242.

    Article  PubMed  PubMed Central  Google Scholar 

  109. Parodi A, Quattrocchi N, van de Ven AL, et al. Synthetic nanoparticles functionalized with biomimetic leukocyte membranes possess cell-like functions. Nat Nanotechnol. 2013;8(1):61–8.

    Article  CAS  PubMed  Google Scholar 

  110. He Z, Zhang Y, Feng N. Cell membrane-coated nanosized active targeted drug delivery systems homing to tumor cells: a review. Mater Sci Eng C-Mater Biol Appl. 2020;106.

  111. Vijayan V, Uthaman S, Park I-K. Cell membrane-camouflaged nanoparticles: a promising biomimetic strategy for cancer theragnostics. Polymers. 2018;10(9).

  112. Jeppesen DK, Fenix AM, Franklin JL, et al. Reassessment of exosome composition. Cell. 2019;177(2): 428-+.

  113. Barenholz Y. Doxil (R) - The first FDA-approved nano-drug: lessons learned. J Control Release. 2012;160(2):117–34.

    Article  CAS  PubMed  Google Scholar 

  114. Si J, Shao S, Shen Y, et al. Macrophages as active nanocarriers for targeted early and adjuvant cancer chemotherapy. Small. 2016;12(37):5108–19.

    Article  CAS  PubMed  Google Scholar 

  115. Oun R, Moussa YE, Wheate NJ. The side effects of platinum-based chemotherapy drugs: a review for chemists (vol 47, pg 6645, 2018). Dalton Trans. 2018;47(23): 7848-.

  116. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. Ca-a Cancer J Clinic. 2020;70(1):7–30.

    Article  PubMed  Google Scholar 

  117. Dent R, Trudeau M, Pritchard KI, et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res. 2007;13(15):4429–34.

    Article  PubMed  Google Scholar 

  118. Li S, Wu Y, Ding F, et al. Engineering macrophage-derived exosomes for targeted chemotherapy of triple-negative breast cancer. Nanoscale. 2020;12(19):10854–62.

    Article  CAS  PubMed  Google Scholar 

  119. Qiu Y, Ren K, Zhao W, et al. A “dual-guide” bioinspired drug delivery strategy of a macrophage-based carrier against postoperative triple-negative breast cancer recurrence. Journal of controlled release : official journal of the Controlled Release Society. 2020;329:191–204.

    Article  CAS  Google Scholar 

  120. Gong C, Yu X, You B, et al. Macrophage-cancer hybrid membrane-coated nanoparticles for targeting lung metastasis in breast cancer therapy. J Nanobiotechnol. 2020;18(1).

  121. Xiong F, Ling X, Chen X, et al. Pursuing specific chemotherapy of orthotopic breast cancer with lung metastasis from docking nanoparticles driven by bioinspired exosomes. Nano Lett. 2019;19(5):3256–66.

    Article  CAS  PubMed  Google Scholar 

  122. Li P, Gao M, Hu Z, et al. Synergistic ferroptosis and macrophage re-polarization using engineering exosome-mimic M1 nanovesicles for cancer metastasis suppression. Chem Eng J. 2021;409.

  123. Haney MJ, Zhao Y, Jin YS, et al. Macrophage-derived extracellular vesicles as drug delivery systems for triple negative breast cancer (TNBC) therapy. J Neuroimmune Pharmacol. 2020;15(3):487–500.

    Article  PubMed  Google Scholar 

  124. Rayamajhi S, Nguyen TDT, Marasini R, et al. Macrophage-derived exosome-mimetic hybrid vesicles for tumor targeted drug delivery. Acta Biomater. 2019;94:482–94.

    Article  CAS  PubMed  Google Scholar 

  125. Cao H, Wang H, He X, et al. Bioengineered macrophages can responsively transform into nanovesicles to target lung metastasis. Nano Lett. 2018;18(8):4762–70.

    Article  CAS  PubMed  Google Scholar 

  126. Kim MS, Haney MJ, Zhao Y, et al. Development of exosome-encapsulated paclitaxel to overcome MDR in cancer cells. Nanomed Nanotechnol Biol Med. 2016;12(3):655–64.

    Article  CAS  PubMed  Google Scholar 

  127. Zhang X, Liu L, Tang M, et al. The effects of umbilical cord-derived macrophage exosomes loaded with cisplatin on the growth and drug resistance of ovarian cancer cells. Drug Dev Ind Pharm. 2020;46(7):1150–62.

    Article  CAS  PubMed  Google Scholar 

  128. Leonard F, Curtis LT, Yesantharao P, et al. Enhanced performance of macrophage-encapsulated nanoparticle albumin-bound-paclitaxel in hypo-perfused cancer lesions. Nanoscale. 2016;8(25):12544–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Li J, Li N, Wang J. M1 macrophage-derived exosome-encapsulated cisplatin can enhance its anti-lung cancer effect. Minerva medica. 2020.

  130. Deng X, Shao Z, Zhao Y. Solutions to the drawbacks of photothermal and photodynamic cancer therapy. Adv Sci. 2021;8(3).

  131. Li Y, Li X, Zhou F, et al. Nanotechnology-based photoimmunological therapies for cancer. Cancer Lett. 2019;442:429–38.

    Article  CAS  PubMed  Google Scholar 

  132. Huang X, Jain PK, El-Sayed IH, et al. Plasmonic photothermal therapy (PPTT) using gold nanoparticles. Lasers Med Sci. 2008;23(3):217–28.

    Article  PubMed  Google Scholar 

  133. Cheng L, Wang C, Feng L, et al. Functional nanomaterials for phototherapies of cancer. Chem Rev. 2014;114(21):10869–939.

    Article  CAS  PubMed  Google Scholar 

  134. Riley RS, Day ES. Gold nanoparticle-mediated photothermal therapy: applications and opportunities for multimodal cancer treatment. Wiley Interdiscip Rev Nanomed Nanobiotech. 2017;9(4).

  135. Wang Z, Chang Z, Lu M, et al. Janus silver/silica nanoplatforms for light-activated liver cancer chemo/photothermal therapy. ACS Appl Mater Interfaces. 2017;9(36):30306–17.

    Article  CAS  PubMed  Google Scholar 

  136. Hu Y, Hu H, Yan J, et al. Multifunctional porous iron oxide nanoagents for MRI and photothermal/chemo synergistic therapy. Bioconjug Chem. 2018;29(4):1283–90.

    Article  CAS  PubMed  Google Scholar 

  137. Meng Q-F, Rao L, Zan M, et al. Macrophage membrane-coated iron oxide nanoparticles for enhanced photothermal tumor therapy. Nanotech. 2018;29(13).

  138. Xuan M, Shao J, Dai L, et al. Macrophage cell membrane camouflaged Au nanoshells for in vivo prolonged circulation life and enhanced cancer photothermal therapy. ACS Appl Mater Interfaces. 2016;8(15):9610–8.

    Article  CAS  PubMed  Google Scholar 

  139. Liu Y, Bhattarai P, Dai Z, et al. Photothermal therapy and photoacoustic imaging via nanotheranostics in fighting cancer. Chem Soc Rev. 2019;48(7):2053–108.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Yousaf T, Dervenoulas G, Politis M. Advances in MRI methodology [M]//POLITIS M. Imaging in Movement Disorders: Imaging Methodology and Applications in Parkinson's Disease. 2018: 31–76.

  141. Rayamajhi S, Marasini R, Tuyen Duong Thanh N, et al. Strategic reconstruction of macrophage-derived extracellular vesicles as a magnetic resonance imaging contrast agent. Biomater Sci. 2020;8(10): 2887–904.

  142. Sier VQ, De Vries MR, Van Der Vorst JR, et al. Cell-Based tracers as Trojan horses for image-guided surgery. Int J Mol Sci. 2021;22(2).

  143. Guidotti G, Brambilla L, Rossi D. Cell-penetrating peptides: from basic research to clinics. Trends Pharmacol Sci. 2017;38(4):406–24.

    Article  CAS  PubMed  Google Scholar 

  144. Abbott NJ, Patabendige AAK, Dolman DEM, et al. Structure and function of the blood-brain barrier. Neurobiol Dis. 2010;37(1):13–25.

    Article  CAS  PubMed  Google Scholar 

  145. Pardridge WM. The blood-brain barrier: bottleneck in brain drug development. NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics. 2005;2(1):3–14.

    Article  Google Scholar 

  146. Madsen SJ, Gach HM, Hong SJ, et al. Increased nanoparticle-loaded exogenous macrophage migration into the brain following PDT-induced blood-brain barrier disruption. Lasers Surg Med. 2013;45(8):524–32.

    Article  PubMed  PubMed Central  Google Scholar 

  147. Lu M, Huang Y. Bioinspired exosome-like therapeutics and delivery nanoplatforms. Biomater. 2020;242.

  148. Tian T, Zhang H-X, He C-P, et al. Surface functionalized exosomes as targeted drug delivery vehicles for cerebral ischemia therapy. Biomater. 2018;150: 137–49.

  149. Beeraka NM, Doreswamy SH, Sadhu SP, et al. The role of exosomes in stemness and neurodegenerative diseases-chemoresistant-cancer therapeutics and phytochemicals. Int J Mol Sci. 2020;21(18).

  150. Huang S, Ge X, Yu J, et al. Increased miR-124-3p in microglial exosomes following traumatic brain injury inhibits neuronal inflammation and contributes to neurite outgrowth via their transfer into neurons. FASEB J. 2018;32(1):512–28.

    Article  CAS  PubMed  Google Scholar 

  151. Gupta A, Pulliam L. Exosomes as mediators of neuroinflammation. J Neuroinflammation. 2014;11.

  152. Batrakova EV. Macrophage-derived extracellular vesicles target inflamed brain and deliver therapeutic proteins for treatment of neurodegenerative disorders. J Neuroimmune Pharmacol. 2019;14(2): 336-.

  153. Poewe W, Seppi K, Tanner CM, et al. Parkinson disease. Nat Rev Dis Primers. 2017;3.

  154. Lane CA, Hardy J, Schott JM. Alzheimer’s disease. Eur J Neurol. 2018;25(1):59–70.

    Article  CAS  PubMed  Google Scholar 

  155. Haney MJ, Klyachko NL, Zhaoa Y, et al. Exosomes as drug delivery vehicles for Parkinson’s disease therapy. J Control Release. 2015;207:18–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Han Y, Gao C, Wang H, et al. Macrophage membrane-coated nanocarriers Co-modified by RVG29 and TPP improve brain neuronal mitochondria-targeting and therapeutic efficacy in Alzheimer’s disease mice. Bioact Mater. 2021;6(2):529–42.

    Article  CAS  PubMed  Google Scholar 

  157. Yao J, Wang Z, Cheng Y, et al. M2 macrophage-derived exosomal microRNAs inhibit cell migration and invasion in gliomas through PI3K/AKT/mTOR signaling pathway. J Transl Med. 2021;19(1).

  158. Li J, Kong J, Ma S, et al. Exosome-coated B-10 carbon dots for precise boron neutron capture therapy in a mouse model of glioma in situ. Adv Funct Mater. 2021.

  159. Li F, Zhao L, Shi Y, et al. Edaravone-loaded macrophage-derived exosomes enhance neuroprotection in the rat permanent middle cerebral artery occlusion model of stroke. Mol Pharm. 2020;17(9):3192–201.

    Article  CAS  PubMed  Google Scholar 

  160. Tabas I, Bornfeldt KE. Macrophage phenotype and function in different stages of atherosclerosis. Circ Res. 2016;118(4):653–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Virani SS, Alonso A, Benjamin EJ, et al. Heart disease and stroke statistics—2020 update: a report from the American Heart Association. Circulation. 2020;141(9):E139–596.

    Article  PubMed  Google Scholar 

  162. Chinetti-Gbaguidi G, Colin S, Staels B. Macrophage subsets in atherosclerosis. Nat Rev Cardiol. 2015;12(1):10–7.

    Article  CAS  PubMed  Google Scholar 

  163. Cao H, Dan Z, He X, et al. Liposomes coated with isolated macrophage membrane can target lung metastasis of breast cancer. ACS Nano. 2016;10(8):7738–48.

    Article  CAS  PubMed  Google Scholar 

  164. Peng R, Ji H, Jin L, et al. Macrophage-based therapies for atherosclerosis management. J Immunol Res. 2020;2020.

  165. Bouchareychas L, Phat D, Covarrubias S, et al. Macrophage exosomes resolve atherosclerosis by regulating hematopoiesis and inflammation via MicroRNA cargo. Cell Rep. 2020;32(2).

  166. Wang Y, Zhang K, Li T, et al. Macrophage membrane functionalized biomimetic nanoparticles for targeted anti-atherosclerosis applications. Theranostics. 2021;11(1):164–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Gao C, Huang Q, Liu C, et al. Treatment of atherosclerosis by macrophage-biomimetic nanoparticles via targeted pharmacotherapy and sequestration of proinflammatory cytokines. Nat Commun. 2020;11(1).

  168. Kapoor G, Saigal S, Elongavan A. Action and resistance mechanisms of antibiotics: a guide for clinicians. J Anaesthesiol Clin Pharmacol. 2017;33(3):300–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Aslam B, Wang W, Arshad MI, et al. Antibiotic resistance: a rundown of a global crisis. Infect Drug Resist. 2018;11:1645–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Wang C, Wang Y, Zhang L, et al. Pretreated macrophage-membrane-coated gold nanocages for precise drug delivery for treatment of bacterial infections. Adv Mater. 2018;30(46).

  171. Qin M, Du G, Sun X. Biomimetic cell-derived nanocarriers for modulating immune responses. Biomater Sci. 2020;8(2):530–43.

    Article  CAS  PubMed  Google Scholar 

  172. Li J, Wang Y, Yang J, et al. Bacteria activated-macrophage membrane-coated tough nanocomposite hydrogel with targeted photothermal antibacterial ability for infected wound healing. Chem Eng J. 2021;420: 127638.

  173. Fu J, Li Y, Zhang Y, et al. An engineered pseudo-macrophage for rapid treatment of bacteria-infected osteomyelitis via microwave-excited anti-infection and immunoregulation. Adv Mater. 2021;33(41):2102926.

    Article  CAS  Google Scholar 

  174. Cypryk W, Lorey M, Puustinen A, et al. Proteomic and bioinformatic characterization of extracellular vesicles released from human macrophages upon influenza A virus infection. J Proteome Res. 2017;16(1):217–27.

    Article  CAS  PubMed  Google Scholar 

  175. Wu W, Wu D, Yan W, et al. Interferon-induced macrophage-derived exosomes mediate antiviral activity against hepatitis B virus through miR-574-5p. J Infect Dis. 2021;223(4):686–98.

    Article  CAS  PubMed  Google Scholar 

  176. Cai C, Koch B, Morikawa K, et al. Macrophage-derived extracellular vesicles induce long-lasting immunity against hepatitis C virus which is blunted by polyunsaturated fatty acids. Front Immunol. 2018;9:723.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  177. Kouwaki T, Okamotto M, Tsukamoto H, et al. Extracellular vesicles deliver host and virus RNA and regulate innate immune response. Int J Mol Sci 2017;18(3).

  178. Li R, He Y, Zhu Y, et al. Route to rheumatoid arthritis by macrophage-derived microvesicle-coated nanoparticles. Nano Lett. 2019;19(1):124–34.

    Article  CAS  PubMed  Google Scholar 

  179. He H, Ghosh S, Yang H. Nanomedicines for dysfunctional macrophage-associated diseases. J Control Release. 2017;247:106–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  180. YAN F, ZHONG Z, WANG Y, et al. Exosome-based biomimetic nanoparticles targeted to inflamed joints for enhanced treatment of rheumatoid arthritis. J Nanobiotechnol. 2020;18(1).

  181. Thamphiwatana S, Angsantikul P, Escajadillo T, et al. Macrophage-like nanoparticles concurrently absorbing endotoxins and proinflammatory cytokines for sepsis management. Proc Natl Acad Sci USA. 2017;114(43):11488–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. Molinaro R, Pasto A, Corbo C, et al. Macrophage-derived nanovesicles exert intrinsic anti-inflammatory properties and prolong survival in sepsis through a direct interaction with macrophages. Nanoscale. 2019;11(28):13576–86.

    Article  CAS  PubMed  Google Scholar 

  183. Sun T, Kwong CHT, Gao C, et al. Amelioration of ulcerative colitis via inflammatory regulation by macrophage-biomimetic nanomedicine. Theranostics. 2020;10(22):10106–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. Yurkin ST, Wang Z. Cell membrane-derived nanoparticles: emerging clinical opportunities for targeted drug delivery. Nanomedicine. 2017;12(16):2007–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  185. Spiller KL, Koh TJ. Macrophage-based therapeutic strategies in regenerative medicine. Adv Drug Deliv Rev. 2017;122:74–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  186. Ou Z, Zhong H, Zhang L, et al. Macrophage membrane-coated nanoparticles alleviate hepatic ischemia-reperfusion injury caused by orthotopic liver transplantation by neutralizing endotoxin. Int J Nanomed. 2020;15:4125–38.

    Article  CAS  Google Scholar 

  187. Jin Y, Liu R, Xie J, et al. Interleukin-10 deficiency aggravates kidney inflammation and fibrosis in the unilateral ureteral obstruction mouse model. Lab Invest. 2013;93(7):801–11.

    Article  CAS  PubMed  Google Scholar 

  188. Tang T-T, Wang B, Wu M, et al. Extracellular vesicle-encapsulated IL-10 as novel nanotherapeutics against ischemic AKI. Sci Adv. 2020;6(33).

  189. Kumar P, Bose PP. Macrophage ghost entrapped amphotericin B: a novel delivery strategy towards experimental visceral leishmaniasis. Drug Deliv Transl Res. 2019;9(1):249–59.

    Article  CAS  PubMed  Google Scholar 

  190. Nie W, Wu G, Zhang J, et al. Responsive exosome nano-bioconjugates for synergistic cancer therapy. Angewandte Chemie-International Edition. 2020;59(5):2018–22.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

The work was supported by the Hunan Provincial Science and Technology Plan (No. 2016TP2002).

Author information

Authors and Affiliations

  1. Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China

    Wen-Jie Xu, Jia-Xin Cai, Yong-Jiang Li, Jun-Yong Wu & Daxiong Xiang

  2. Institute of Clinical Pharmacy, Central South University, Changsha, 410011, Hunan, China

    Wen-Jie Xu, Jia-Xin Cai, Yong-Jiang Li, Jun-Yong Wu & Daxiong Xiang

  3. Hunan Provincial Engineering Research Center of Translational Medicine and Innovative Drug, Hunan Province, Changsha, China

    Wen-Jie Xu, Jia-Xin Cai, Yong-Jiang Li, Jun-Yong Wu & Daxiong Xiang

Authors
  1. Wen-Jie Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jia-Xin Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yong-Jiang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jun-Yong Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Daxiong Xiang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

X.-W.J. and C.-J.X. formulated the idea. X.-W.J. made the figure and wrote the manuscript. C.-J.X. made the table. L.-Y.J., C.-J.X., and W.-J.Y. critically revised the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Daxiong Xiang.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

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.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xu, WJ., Cai, JX., Li, YJ. et al. Recent progress of macrophage vesicle-based drug delivery systems. Drug Deliv. and Transl. Res. 12, 2287–2302 (2022). https://doi.org/10.1007/s13346-021-01110-5

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13346-021-01110-5

Keywords

Search

Navigation