Platelet-promoting drug delivery efficiency for inhibition of tumor growth, metastasis, and recurrence

Abstract

Nanomedicines are considered one of the promising strategies for anticancer therapy; however, the low targeting efficiency of nanomedicines in vivo is a great obstacle to their clinical applications. Camouflaging nanomedicines with either platelet membrane (PM) or platelet would significantly prolong the retention time of nanomedicines in the bloodstream, enhance the targeting ability of nanomedicines to tumor cells, and reduce the off-target effect of nanomedicines in major organs during the anticancer treatment. In the current review, the advantages of using PM or platelet as smart carriers for delivering nanomedicines to inhibit tumor growth, metastasis, and recurrence were summarized. The opportunities and challenges of this camouflaging strategy for anticancer treatment were also discussed.

Keywords: anticancer therapy; delivery system; nanomedicine; platelet; platelet membrane.

Figure 1

The five-step CAPIR cascade for nanomedicines to deliver free drugs into tumor cells. C step: nanomedicines should be stable and stealthy for long blood circulation, which means nanomedicines should be large (about 100 nm), and the surface should be pegylated and neutral and hide binding groups. A step: nanomedicines should specifically accumulate in tumor site through enhanced permeability and retention (EPR) effect and interaction between the surface ligand on nanomedicines and receptors on tumors. P step: nanomedicines should be small (less than 30 nm) and show a positive charge on the surface for effective tumor penetration. I step: nanomedicines should show positive charge and specific ligands/functional groups on surface to stick to tumor cells for fast cellular internalization. R step: nanomedicines should release the active drug in a “smart” manner modulated by tumor microenvironment (TME) characteristics (5, 6). Figure reproduced with permission (4). Copyright, 2014 WILEY‐VCH (License Number: 5325080186333).

Figure 2

Platelets stimulate tumor angiogenesis, enhance vascular permeability, and promote the formation of metastatic tumors. Platelets stimulate tumor angiogenesis through the release of angiogenesis regulator factors, such as vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF), after activation in the tumor site; platelets trigger epithelial–mesenchymal transition (EMT) activation to enhance vascular permeability of tumor cell; circulating tumor cells (CTCs) binding with platelets are protected from shear stress and immune elimination.

Figure 3

Preparation of platelet membrane (PM)-coated nanomedicines used for inhibiting tumor growth and metastasis. The isolated platelets from whole blood were fragmented by freeze–thaw cycles assisted by sonication and purified by centrifugation to give the desired PM (18). Then the PM fused with nanomedicines to form PM-cloaked nanomedicines for inhibiting tumor growth and metastasis.

Figure 4

Platelet-loaded nanomedicine for inhibiting tumor growth and metastasis through chemotherapy, immunotherapy, or photothermal tumor therapy (PTT). Purified platelets were obtained from the whole blood by centrifugation. Then the nanomedicines were loaded into the platelet through electroporation methods to form a platelet-loaded nanomedicine system. After intravenous injection, the platelet-loaded nanomedicines would interact with tumor cells through adhesion and activation, and the loaded medicines are released for inhibiting tumor growth and metastasis through chemotherapy, immunotherapy, or PTT.