期刊
JOURNAL OF MATERIALS CHEMISTRY B
卷 6, 期 19, 页码 3163-3180出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/c8tb00319j
关键词
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资金
- Major Project of Education Department in Sichuan [17ZA0117]
- National Natural Science Foundation of China [81603045]
- Natural Science Foundation of Chengdu Medical College [15Z103]
The safe and efficient targeted delivery of chemotherapeutic drugs has remained a challenge in metastatic breast cancer therapy. Herein, we report a rational drug delivery strategy of co-administering tumor-penetrating peptide-iRGD with self-assembled amphiphilic block copolymer nanoparticles (HA-PLA) to inhibit tumor growth and lung metastasis in 4T1 breast cancer xenograft bearing mice through increasing drug accumulation in the tumors, inducing receptor-mediated tumor cell targeting without causing severe side effects. In vitro, HA-PLA displayed sustained and pH-sensitive release behavior. The cellular uptake of HA-PLA on high CD44-expressing 4T1 cells was significantly higher than the endocytosis on low CD44-expressing L929 fibroblast cells. In vivo, HA-PLA significantly extended the blood circulation time of DOX, displayed no accelerated blood clearance (ABC) phenomenon after repeated injection and decreased the side effects of DOX. When combined with iRGD, the drug distribution and penetration of HA-PLA in tumors were remarkably increased, resulting in better antitumor efficacy and the longest whole survival. In particular, the co-administration of iRGD with HA-PLA greatly increased drug distribution in the lung, which contributed to the effective inhibition of the lung metastasis of breast cancer. Therefore, co-administering iRGD with HA-PLA is a promising approach for metastatic breast cancer therapy.
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