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Platelet-membrane-biomimetic nanoparticles for targeted antitumor drug delivery

Haijun WangCollege of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, 201620, ChinaJunzi WuCollege of Basic Medicine, Yunnan University of Traditional Chinese Medicine, Kunming, 650500, China. [email protected]Gareth R. WilliamsUCL School of Pharmacy, University College London, 29-39 Brunswick Square, London, WC1N 1AX, UKQing FanDepartment of Pharmacy, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Science, Jinan, 250117, ChinaShiwei NiuCollege of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, 201620, ChinaXiaotian XieCollege of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, 201620, ChinaLi‐Min ZhuCollege of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, 201620, China. [email protected]

2019en

ABI

Annotatsiya

BACKGROUND: Nanoscale drug-delivery systems (DDSs) have great promise in tumor diagnosis and treatment. Platelet membrane (PLTM) biomimetic DDSs are expected to enhance retention in vivo and escape uptake by macrophages, as well as minimizing immunogenicity, attributing to the CD47 protein in PLTM sends "don't eat me" signals to macrophages. In addition, P-selectin is overexpressed on the PLTM, which would allow a PLTM-biomimetic DDS to specifically bind to the CD44 receptors upregulated on the surface of cancer cells. RESULTS: In this study, porous nanoparticles loaded with the anti-cancer drug bufalin (Bu) were prepared from a chitosan oligosaccharide (CS)-poly(lactic-co-glycolic acid) (PLGA) copolymer. These were subsequently coated with platelet membrane (PLTM) to form PLTM-CS-pPLGA/Bu NPs. The PLTM-CS-pPLGA/Bu NPs bear a particle size of ~ 192 nm, and present the same surface proteins as the PLTM. Confocal microscopy and flow cytometry results revealed a greater uptake of PLTM-CS-pPLGA/Bu NPs than uncoated CS-pPLGA/Bu NPs, as a result of the targeted binding of P-selectin on the surface of the PLTM to the CD44 receptors of H22 hepatoma cells. In vivo biodistribution studies in H22-tumor carrying mice revealed that the PLTM-CS-pPLGA NPs accumulated in the tumor, because of a combination of active targeting effect and the EPR effect. The PLTM-CS-pPLGA/Bu NPs led to more effective tumor growth inhibition over other bufalin formulations. CONCLUSIONS: Platelet membrane biomimetic nanoparticles played a promising targeted treatment of cancer with low side effect.

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DOI: 10.1186/s12951-019-0494-y

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