1. Lipid insertion enables targeted functionalization of paclitaxel-loaded erythrocyte membrane nanosystem by tumor-penetrating bispecific recombinant protein.
- Author
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Chen H, Sha H, Zhang L, Qian H, Chen F, Ding N, Ji L, Zhu A, Xu Q, Meng F, Yu L, Zhou Y, and Liu B
- Subjects
- Animals, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Antineoplastic Agents therapeutic use, Cell Death drug effects, Cell Line, Tumor, Drug Delivery Systems, ErbB Receptors metabolism, Erythrocyte Membrane drug effects, Erythrocyte Membrane ultrastructure, Erythrocytes drug effects, Erythrocytes metabolism, Fluorescence, Humans, Male, Mice, Inbred BALB C, Mice, Nude, Neoplasms pathology, Oligopeptides metabolism, Paclitaxel chemistry, Paclitaxel therapeutic use, Phosphatidylethanolamines chemistry, Polyethylene Glycols chemistry, Tissue Distribution drug effects, Erythrocyte Membrane metabolism, Lipids chemistry, Nanoparticles chemistry, Neoplasms drug therapy, Paclitaxel pharmacology, Recombinant Proteins pharmacology
- Abstract
Background: There is currently much interest in cancer cell targeting and tumor penetrating for research and therapeutic purposes., Purpose: To improve targeting delivery of antitumor drugs to gastric cancer, in this study, a tumor-targeting biocompatible drug delivery system derived from erythrocyte membrane for delivering paclitaxel (PTX) was constructed., Methods: Erythrocyte membrane of human red blood cells (RBCs) were used for preparing of erythrocyte membrane-derived vesicles. 1,2-distearoyl- sn -glycero-3-phosphoethanolamine- N -(maleimide[polyethylene glycol]-3400) (DSPE-PEG-MAL), a phospholipid derivative, was used to insert tumor-targeting molecular into erythrocyte membrane-derived vesicles. A lipid insertion method was used to functionalize these vesicles without the need for direct chemical conjugation. Furthermore, a tumor-penetrating bispecific recombinant protein named anti-EGFR-iRGD was used for the first time in this work to enable nanosystem to target and penetrate efficiently into the tumor site., Results: Paclitaxel (PTX)-loaded anti-EGFR-iRGD-modified erythrocyte membrane nano-system (anti-EGFR-iRGD-RBCm-PTX, abbreviated to PRP) were manufactured. PRP was spheroid, uniformly size, about 171.7±4.7 nm in average, could be stable in vitro for 8 days, and released PTX in a biphasic pattern. PRP showed comparable cytotoxicity toward human gastric cancer cells in vitro. In vivo studies showed that, PRP accumulated in tumor site within 2 h of administration, lasted longer than 48 h, and the tumor volume was reduced 61% by PRP treatment in Balb/c nude mice, without causing severe side effects., Conclusion: PRP has potential applications in cancer treatment and as an adjunct for other anticancer strategies., Competing Interests: Disclosure The authors report no conflicts of interest in this work.
- Published
- 2018
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