Co-administration of biocompatible self-assembled polylactic acid–hyaluronic acid block copolymer nanoparticles with tumor-penetrating peptide-iRGD for metastatic breast cancer therapy
| Autor: | Drunp Tashi, Caifeng Deng, Bingyin Su, Xiaohong Xu, Quan Zhang, Yongmei Wu |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Biomedical Engineering
02 engineering and technology 010402 general chemistry Endocytosis 01 natural sciences chemistry.chemical_compound Breast cancer In vivo Hyaluronic acid medicine General Materials Science Lung business.industry General Chemistry General Medicine respiratory system 021001 nanoscience & nanotechnology medicine.disease Metastatic breast cancer In vitro 0104 chemical sciences medicine.anatomical_structure chemistry Drug delivery Cancer research 0210 nano-technology business |
| Zdroj: | Journal of Materials Chemistry B. 6:3163-3180 |
| ISSN: | 2050-7518 2050-750X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|