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. Electronic supplementary material The online version of this article (10.1186/s12951-019-0494-y) contains supplementary material, which is available to authorized users.
24In this study, we developed novel thermal and redox-responsive micelles based on the Pluronic 25 F127 tri-block copolymer and employed these for redox-responsive intratumor release of bufalin, an 26 anti-cancer drug. Pluronic F127 was first functionalized with carboxylate groups, and then assembled 27 into micelles. The HOOC-F127-COOH micelles are 20 ± 4 nm in size at 37 ºC, but expand to 281 ± 5 28 nm when cooled to 4 ºC. This allows for the free diffusion of bufalin into the micellar cores at low 29 temperatures, while at 37 ºC the micelles are much more compact and the drug molecules can be 30 effectively held in their interiors. A high encapsulation efficiency and loading content were obtained 31 via drug incorporation at 4 ºC. The drug-loaded micelles were cross-linked with cystamine, which 32 contains a disulfide bond responsive to the local cancer microenvironment. In vitro studies showed that 33 drug release from the cross-linked micelles was low under normal physiological conditions, but 34 markedly accelerated upon exposure to conditions representative of the intracellular tumor environment. 35Confocal microscopy revealed that the cross-linked micelles gave high levels of drug release inside the 36 cells. In vivo studies in mice showed the drug-loaded cross-linked micelles have potent anti-tumor 37 activities, leading to high levels of apoptosis of tumor cells and significant reductions in tumor volume. 38The drug-loaded cross-linked micelles did not significantly influence body weight, and there was no 39 evidence for detrimental off-target effects. These results indicate that the Pluronic-based micelles 40 developed in this work are promising drug delivery systems for the targeted treatment of cancer. 41 42 43
Herein, we developed curcumin (Cur)-loaded porous poly(lactic-co-glycolic acid) (pPLGA) nanoparticles (NPs) by the nanoprecipitation method. Dopamine (DA) was then selfpolymerized to form a polydopamine (PDA) layer on the surface of the NPs, yielding Cur@pPLGA/PDA NPs able to act as both chemotherapeutic and photothermal agents. These NPs were further camouflaged with the red blood cell membrane (RBCM) to construct RBCM-Cur@pPLGA/PDA NPs. The RBCM-pPLGA/PDA NPs were around 200 nm in size, demonstrated photothermal performance in the NIR region with a potent photothermal conversion efficiency (35.2%). The blank carrier has favorable cytocompatibility, but when drug loaded can efficiently induce the death of cancer cells (particularly when combined with an NIR laser treatment). Cellular uptake results revealed greater in vitro uptake of RBCM-Cur@pPLGA/PDA NPs than bare Cur@pPLGA/PDA NPs in the case of cancer cells, but reduced macrophage phagocytosis. In vivo studies in mice showed the RBCM-Cur@pPLGA/PDA NPs exhibited prolonged blood circulation times and superior photothermal effect (>43 ℃) for tumor specific chemo-photothermal therapy.The RBCM-Cur@pPLGA/PDA NP platform presents great potential for targeted synergistic cancer treatments.
In this study, curcumin-loaded porous poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) were prepared and surface modified with red blood cell membranes (RBCM) to yield biomimetic RBCM-p-PLGA@Cur NPs. The NPs displayed a visible cell-membrane structure at their exterior and had a uniform size of 162 ± 3 nm. In vitro studies showed that drug release from non-porous PLGA NPs was slow and that much of the drug remained trapped in the NPs. In contrast, release was accelerated from the porous PLGA NPs, and after the RBCM coating, a sustained release over 48 h was obtained. Confocal microscopy and flow cytometry results revealed that the RBCM-p-PLGA NPs led to a greater cellular uptake by H22 hepatocarcinoma cells than the uncoated analogue NPs, but could avoid phagocytosis by macrophages. The drug-free formulations were highly biocompatible, while the drug-loaded systems were effective in killing cancer cells. RBCM-p-PLGA@Cur NPs possess potent anti-tumor activity in a murine H22 xenograft cancer model (in terms of reduced tumor volume and mass, as well as inducing apoptosis of tumor cells), and have no observable systemic toxicity. Overall, our study demonstrates that the use of the RBCM to cloak nanoscale drug delivery systems holds great promise for targeted cancer treatment, and can ameliorate the severe side effects currently associated with chemotherapy.
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