Platelet membrane-based and tumor-associated platelet- targeted drug delivery systems for cancer therapy

Abstract

Platelets have long been known to play critical roles in hemostasis by clumping and clotting blood vessel injuries. Recent experimental evidence strongly indicates that platelets can also interact with tumor cells by direct binding or secreting cytokines. For example, platelets have been shown to protect circulating cancer cells in blood circulation and to promote tumor metastasis. In-depth understanding of the role of platelets in cancer progression and metastasis provides promising approaches for platelet biomimetic drug delivery systems and functional platelet-targeting strategies for effective cancer treatment. This review highlights recent progresses in platelet membrane-based drug delivery and unique strategies that target tumor-associated platelets for cancer therapy. The paper also discusses future development opportunities and challenges encountered for clinical translation.

Keywords

platelet-mimicking delivery systems / tumor-associated platelets / cancer therapy / EPR effect

References

[1] Gurtner GC, Werner S, Barrandon Y, Longaker MT. Wound repair and regeneration. Nature 2008; 453(7193): 314–321

[2] Furie B, Furie BC. Thrombus formation in vivo. J Clin Invest 2005; 115(12): 3355–3362

[3] Ho-Tin-Noé B, Goerge T, Cifuni SM, Duerschmied D, Wagner DD. Platelet granule secretion continuously prevents intratumor hemorrhage. Cancer Res 2008; 68(16): 6851–6858

[4] Gay LJ, Felding-Habermann B. Contribution of platelets to tumour metastasis. Nat Rev Cancer 2011; 11(2): 123–134

[5] Quail DF, Joyce JA. Microenvironmental regulation of tumor progression and metastasis. Nat Med 2013; 19(11): 1423–1437

[6] Mammadovabach E, Zigrino P, Brucker C, Bourdon C, Freund M, Arcangelis AD, Abrams SI, Orend G, Gachet C, Mangin PH. Platelet integrin a6b1 controls lung metastasis through direct binding to cancer cell–derived ADAM9. JCI Insight 2016; 1(14): e88245

[7] Yu LX, Yan L, Yang W, Wu FQ, Ling Y, Chen SZ, Tang L, Tan YX, Cao D, Wu MC, Yan HX, Wang HY. Platelets promote tumour metastasis via interaction between TLR4 and tumour cell-released high-mobility group box1 protein. Nat Commun 2014; 5: 5256

[8] Xu P, Zuo H, Chen B, Wang R, Ahmed A, Hu Y, Ouyang J. Doxorubicin-loaded platelets as a smart drug delivery system: an improved therapy for lymphoma. Sci Rep 2017; 7: 42632

[9] Nurden AT, Nurden P, Sanchez M, Andia I, Anitua E. Platelets and wound healing. Front Biosci 2008; 13: 3532–3548

[10] Nieswandt B, Hafner M, Echtenacher B, Männel DN. Lysis of tumor cells by natural killer cells in mice is impeded by platelets. Cancer Res 1999; 59(6): 1295–1300

[11] Wang C, Sun W, Ye Y, Hu Q, Bomba HN, Gu Z. In situ activation of platelets with checkpoint inhibitors for post-surgical cancer immunotherapy. Nat Biomed Eng 2017; 1: 0011

[12] Daly ME. Determinants of platelet count in humans. Haematologica 2011; 96(1): 10–13

[13] Li J, Sharkey CC, Wun B, Liesveld JL, King MR. Genetic engineering of platelets to neutralize circulating tumor cells. J Control Release 2016; 228: 38–47

[14] Hu CM, Fang RH, Wang KC, Luk BT, Thamphiwatana S, Dehaini D, Nguyen P, Angsantikul P, Wen CH, Kroll AV, Carpenter C, Ramesh M, Qu V, Patel SH, Zhu J, Shi W, Hofman FM, Chen TC, Gao W, Zhang K, Chien S, Zhang L. Nanoparticle biointerfacing by platelet membrane cloaking. Nature 2015; 526(7571): 118–121

[15] Dehaini D, Wei X, Fang RH, Masson S, Angsantikul P, Luk BT, Zhang Y, Ying M, Jiang Y, Kroll AV, Gao W, Zhang L. Erythrocyte-platelet hybrid membrane coating for enhanced nanoparticle functionalization. Adv Mater 2017 29(16):1606209

[16] Hu Q, Sun W, Qian C, Wang C, Bomba HN, Gu Z. Anticancer platelet-mimicking nanovehicles. Adv Mater 2015; 27(44): 7043–7050

[17] Hu Q, Qian C, Sun W, Wang J, Chen Z, Bomba HN, Xin H, Shen Q, Gu Z. Engineered nanoplatelets for enhanced treatment of multiple myeloma and thrombus. Adv Mater 2016; 28(43): 9573–9580

[18] Hu Q, Sun W, Qian C, Bomba HN, Xin H, Gu Z. Relay drug delivery for amplifying targeting signal and enhancing anticancer efficacy. Adv Mater 2017; 29(13): 1605803

[19] Li J, Ai Y, Wang L, Bu P, Sharkey CC, Wu Q, Wun B, Roy S, Shen X, King MR. Targeted drug delivery to circulating tumor cells via platelet membrane-functionalized particles. Biomaterials 2016; 76: 52–65

[20] Cho MS, Bottsford-Miller J, Vasquez HG, Stone R, Zand B, Kroll MH, Sood AK, Afshar-Kharghan V. Platelets increase the proliferation of ovarian cancer cells. Blood 2012; 120(24): 4869–4872

[21] Cooke NM, Spillane CD, Sheils O, O’Leary J, Kenny D. Aspirin and P2Y12 inhibition attenuate platelet-induced ovarian cancer cell invasion. BMC Cancer 2015; 15(1): 627

[22] Klement GL, Yip TT, Cassiola F, Kikuchi L, Cervi D, Podust V, Italiano JE, Wheatley E, Abou-Slaybi A, Bender E, Almog N, Kieran MW, Folkman J. Platelets actively sequester angiogenesis regulators. Blood 2009; 113(12): 2835–2842

[23] Rachidi S, Metelli A, Riesenberg B, Wu BX, Nelson MH, Wallace C, Paulos CM, Rubinstein MP, Garrett-Mayer E, Hennig M, Bearden DW, Yang Y, Liu B, Li Z. Platelets subvert T cell immunity against cancer via GARP-TGFb axis. Sci Immunol 2017; 2(11): 7911

[24] Zhang Y, Wei J, Liu S, Wang J, Han X, Qin H, Lang J, Cheng K, Li Y, Qi Y, Anderson GJ, Sukumar S, Li S, Nie G. Inhibition of platelet function using liposomal nanoparticles blocks tumor metastasis. Theranostics 2017; 7(5): 1062–1071

[25] Ho-Tin-Noé B, Goerge T, Wagner DD. Platelets: guardians of tumor vasculature. Cancer Res 2009; 69(14): 5623–5626

[26] Kisucka J, Butterfield CE, Duda DG, Eichenberger SC, Saffaripour S, Ware J, Ruggeri ZM, Jain RK, Folkman J, Wagner DD. Platelets and platelet adhesion support angiogenesis while preventing excessive hemorrhage. Proc Natl Acad Sci USA 2006; 103(4): 855–860

[27] Li S, Zhang Y, Wang J, Zhao Y, Ji T, Zhao X, Ding Y, Zhao X, Zhao R, Li F, Yang X, Liu S, Liu Z, Lai J, Whittaker AK, Anderson GJ, Wei J, Nie G. Nanoparticle-enabled local depletion of tumor-associated platelets disrupts tumor vascular barriers and augments tumor drug accumulation. Nat Biomed Eng 2017;1:667–679

[28] Ishikawa S, Miyashita T, Inokuchi M, Hayashi H, Oyama K, Tajima H, Takamura H, Ninomiya I, Ahmed AK, Harman JW, Fushida S, Ohta T. Platelets surrounding primary tumor cells are related to chemoresistance. Oncol Rep 2016; 36(2): 787–794

Acknowledgements

This work was supported by the National Distinguished Young Scientists Program (No. 31325010), the National Natural Science Foundation of China (No. 31730032), the Innovation Research Group of National Natural Science Foundation of China (No. 11621505), and the Key Research Project of Frontier Science of the Chinese Academy of Sciences (No.QYZDJ-SSW-SLH022).

Compliance with ethics guidelines

Yinlong Zhang, Guangna Liu, Jingyan Wei, and Guangjun Nie declare no conflicts of interests. This manuscript is a review article and does not involve a research protocol requiring approval by any relevant institutional review board or ethics committee.

RIGHTS & PERMISSIONS

2018 Higher Education Press and Springer-Verlag GmbH Germany, part of Springer Nature