Abstract
BackgroundA red blood cell membrane (RBCm)-derived drug delivery system allows prolonged circulation of an antitumor treatment and overcomes the issue of accelerated blood clearance induced by PEGylation. However, RBCm-derived drug delivery systems are limited by low drug-loading capacities and the lack of tumor-targeting ability. Thus, new designs of RBCm-based delivery systems are needed.ResultsHerein, we designed hyaluronic acid (HA)–hybridized RBCm (HA&RBCm)-coated lipid multichambered nanoparticles (HA&RBCm-LCNPs) to remedy the limitations of traditional RBCm drug delivery systems. The inner core co-assembled with phospholipid-regulated glycerol dioleate/water system in HA&RBCm-LCNPs met the required level of blood compatibility for intravenous administration. These newly designed nanocarriers had a honeycomb structure with abundant spaces that efficiently encapsulated paclitaxel and IR780 for photochemotherapy. The HA&RBCm coating allowed the nanocarriers to overcome the reticuloendothelial system barrier and enhanced the nanocarriers specificity to A549 cells with high levels of CD44. These properties enhanced the combinatorial antitumor effects of paclitaxel and IR780 associated with microtubule destruction and the mitochondrial apoptotic pathway.ConclusionsThe multifunctional HA&RBCm-LCNPs we designed expanded the functionality of RBCm and resulted in a vehicle for safe and efficient antitumor treatment.Graphical abstract
Highlights
A red blood cell membrane (RBCm)-derived drug delivery system allows prolonged circulation of an antitumor treatment and overcomes the issue of accelerated blood clearance induced by PEGylation
We further found that the NIR-treated PTX/IR780HA&RBCm-Lipid multi-chamber nanoparticles (LCNPs) promoted apoptosis by destroying the microtubules and by stimulating apoptosis-related proteins, such as the photodynamic therapy (PDT)-induced endogenous mitochondrial apoptotic pathway resulting from the preferential accumulation of IR780 in the mitochondria of tumor cells, which was associated with B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein
The advantages of red blood cells (RBCs) as coated nanoparticle carriers include: (a) a rich source and convenient preparation; (b) escape from the immune system to achieve extended circulation in vivo; (c) good biocompatibility and biodegradability; (d) reduced toxicity when used in certain nano-formulations; and (e) improved stability with reduced aggregation [78]
Summary
A red blood cell membrane (RBCm)-derived drug delivery system allows prolonged circulation of an antitumor treatment and overcomes the issue of accelerated blood clearance induced by PEGylation. RBCm-derived drug delivery systems are limited by low drug-loading capacities and the lack of tumor-targeting ability. For successful drug delivery to tumor tissues, a drug construct must not be eliminated by the reticuloendothelial system (RES) and should achieve prolonged circulation in the blood [6, 7]. A common method for extending the retention time of therapeutics in the blood is through the use of stealth nanoparticles camouflaged with polyethylene glycol (PEG), which increases the hydrophilicity of the constructs and allows escape from RES phagocytosis [8].
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