Inhibition of platelet function using liposomal nanoparticles blocks tumor metastasis

Abstract

Extensive evidence has shown that platelets support tumor metastatic progression by inducing epithelial-mesenchymal transition of cancer cells and by shielding circulating tumor cells from immune-mediated elimination. Therefore, blocking platelet function represents a potential new avenue for therapy focused on eliminating metastasis. Here we show that liposomal nanoparticles bearing the tumor-homing pentapeptide CREKA (Cys-Arg-Glu-Lys-Ala) can deliver a platelet inhibitor, ticagrelor, into tumor tissues to specifically inhibit tumor-associated platelets. The drug-loaded nanoparticles (CREKA-Lipo-T) efficiently blocked the platelet-induced acquisition of an invasive phenotype by tumor cells and inhibited platelet-tumor cell interaction in vitro. Intravenously administered CREKA-Lipo-T effectively targeted tumors within 24 h, and inhibited tumor metastasis without overt side effects. Thus, the CREKA-Lipo formulation provides a simple strategy for the efficient delivery of anti-metastatic drugs and shows considerable promise as a platform for novel cancer therapeutics.

Engineering Biomimetic Platesomes for pH‐Responsive Drug Delivery and Enhanced Antitumor Activity

“…The PEOz‐platesome‐dox also showed satisfactory stability when incubated in phosphate‐buffered saline (PBS) at 4 °C, with no significant change observed in its hydrodynamic diameter or surface charge after 10 days (Figure S2, Supporting Information). When examined by transmission electron microscopy (TEM), both the liposome and platesome (PEOz‐platesome and PEOz‐platesome‐dox) nanoparticles exhibited a typical phospholipid bilayer structure, consistent with previous reports (Figure b) . We also prepared a hybrid platesome with a similar average size (153.6 nm) and surface charge (−32.9 mV) to PEOz‐platesome‐dox but without pH responsiveness by substituting DSPE‐PEOz with DSPE‐PEG2000 (PEG‐platesome‐dox; Table S2, Supporting Information).…”

Enhanced Melanoma‐Targeted Therapy by “Fru‐Blocked” Phenyboronic Acid‐Modified Multiphase Antimetastatic Micellar Nanoparticles

“…The abundant platelets significantly assist tumor metastasis 12, 13, 14, 15, 16. To explore the adhesion between tumor cells and platelets in vitro, platelets were extracted from the blood of male C57BL/6 mice, labeled with calcein AM, and coincubated for 30 min with B16F10 cells treated with PBS, LMWH, LT NPs, or PLT NPs.…”

“…Abundant experimental evidence has indicated that platelets support tumor metastasis by adhering to tumor cells to guard the cells from flow shear stress and immune elimination in blood vessels, helping the cells cross the blood vessel endothelium 12, 13, 14. Platelet secretions also assist tumor cell survival and proliferation within specific distant organs 15, 16.…”

Anti-Metastatic Effects on Melanoma via Intravenous Administration of Anti-NF-κB siRNA Complexed with Functional Peptide-Modified Nano-Micelles

“…According to a report of nanotherapeutics for the treatment of metastasis, poly-ion complex micelles composed of PLL and PEG with a particle size of 30 nm encapsulated in dahaplatin penetrated blood vessels in tumors that had spread to lymph nodes can penetrate deep into the metastasis [13]. In addition, there are cases where tumor metastasis can be suppressed by intravenous administration of liposomal nanoparticles carrying the tumor-homing pentapeptide CREKA without side effects [51]. MPEG-PCL-CH2R4H2C was more effective than naked siRelA and improved siRNA delivery to the metastatic site; therefore, MPEG-PCL-CH2R4H2C indicated as a useful in vivo anti-metastatic siRNA delivery system.…”