Platelet-camouflaged nanococktail: Simultaneous inhibition of drug-resistant tumor growth and metastasis via a cancer cells and tumor vasculature dual-targeting strategy

Abstract

Multidrug resistance (MDR) poses a great challenge to cancer therapy. It is difficult to inhibit the growth of MDR cancer due to its chemoresistance. Furthermore, MDR cancers are more likely to metastasize, causing a high mortality among cancer patients. In this study, a nanomedicine RGD-NPVs@MNPs/DOX was developed by encapsulating melanin nanoparticles (MNPs) and doxorubicin (DOX) inside RGD peptide (c(RGDyC))-modified nanoscale platelet vesicles (RGD-NPVs) to efficiently inhibit the growth and metastasis of drug-resistant tumors via a cancer cells and tumor vasculature dual-targeting strategy.Methods: The in vitro immune evasion potential and the targeting performance of RGD-NPVs@MNPs/DOX were examined using RAW264.7, HUVECs, MDA-MB-231 and MDA-MB-231/ADR cells lines. We also evaluated the pharmacokinetic behavior and the in vivo therapeutic performance of RGD-NPVs@MNPs/DOX using a MDA-MB-231/ADR tumor-bearing nude mouse model.Results: By taking advantage of the self-recognizing property of the platelet membrane and the conjugated RGD peptides, RGD-NPVs@MNPs/DOX was found to evade immune clearance and target the αvβ3 integrin on tumor vasculature and resistant breast tumor cells. Under irradiation with a NIR laser, RGD-NPVs@MNPs/DOX produced a multipronged effect, including reversal of cancer MDR, efficient killing of resistant cells by chemo-photothermal therapy, elimination of tumor vasculature for blocking metastasis, and long-lasting inhibition of the expressions of VEGF, MMP2 and MMP9 within the tumor.Conclusion: This versatile nanomedicine of RGD-NPVs@MNPs/DOX integrating unique biomimetic properties, excellent targeting performance, and comprehensive therapeutic strategies in one formulation might bring opportunities to MDR cancer therapy.

Hybrid cellular membrane nanovesicles amplify macrophage immune responses against cancer recurrence and metastasis

“…More importantly, the NVs contain lipids and proteins of source cells and inherit multiple unique capabilities from the source cells 28 . For example, platelet-derived NVs (P-NVs) can interact with CTCs in the blood and bind to damaged vasculature and tissues [29][30][31][32] ; M1 macrophage-derived NVs (M1-NVs) can repolarize TAMs to an M1-like phenotype 33,34 . Moreover, we have recently reported a facile method for fusing NVs derived from two different types of cells, resulting in hybrid NVs containing characteristics from both source cells 30 .…”

Cell Membrane-Camouflaged Nanocarriers for Cancer Diagnostic and Therapeutic

“…The resulting nanoparticles exhibited synergistic photothermalchemotherapy leading to potent in vivo antitumor efficacy (Liu et al, 2019). In another study, RGD peptide [c(RGDyC)]modified platelet vesicles were employed to co-load melanin nanoparticles (MNPs) and DOX to achieve chemo-photothermal therapy for drug-resistant tumors (Jing et al, 2018). In addition, numerous CM-coated NPs have been developed for cancer photothermal-chemotherapy including RBC-melanoma cell hybrid membrane-coated, DOX-loaded hollow copper sulfide nanoparticles (Wang et al, 2018); RBC-camouflaged, PTX-loaded polymeric NPs (Su et al, 2016); RBCmimetic hollow mesoporous PB NPs (Chen et al, 2017a); and RBC-coated, PTX-loaded gold nanocages (Zhu et al, 2018).…”

Biomimetic Nanocarriers for Cancer Target Therapy

“…Moreover, platelet membrane-coated NPs loaded with DOX and modified with RGD peptides, were shown to be capable of avoiding immune-mediated purging and target cancer vasculature [47]. The unique properties of platelet membrane were employed also by Kim and co-workers to produce platelet membrane-coated gold nanostars containing curcumin with the ability to efficiently target melanoma cancer cells [48].…”