Folate-receptor mediated pH/reduction-responsive biomimetic nanoparticles for dually activated multi-stage anticancer drug delivery
| Autor: | Gui Huang, Ye-juan Zhou, Yu Wang, Hui Li, Wei-liang Chen, Wen-jun Wan, Yang Liu, Ben-gang You, Xue-nong Zhang, Dan-dan Wang |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Cell Survival
Chemistry Pharmaceutical Intracellular pH PH reduction Pharmaceutical Science Antineoplastic Agents 02 engineering and technology Endocytosis 030226 pharmacology & pharmacy Mice 03 medical and health sciences Drug Delivery Systems Folic Acid 0302 clinical medicine In vivo medicine Animals Doxorubicin Cytotoxicity Drug Carriers Mice Inbred BALB C Chemistry technology industry and agriculture Serum Albumin Bovine Hydrogen-Ion Concentration 021001 nanoscience & nanotechnology Drug Liberation Folate receptor Biophysics Nanoparticles Nanocarriers 0210 nano-technology Histamine medicine.drug |
| Zdroj: | International Journal of Pharmaceutics. 585:119456 |
| ISSN: | 0378-5173 |
| DOI: | 10.1016/j.ijpharm.2020.119456 |
| Popis: | How to overcome the cell membrane barriers and achieve release payloads efficiently in the cytoplasm have been major challenges for anticancer drug delivery and therapeutic effects with nanosystems. In this study, bovine serum albumin (BSA) was modified with folate acid and histamine, which was then used as the nanocarrier for the antitumor agent doxorubicin (DOX). The DOX-loaded nanoparticles (DOX/FBH-NPs) were prepared via a crosslinking method, and the release of DOX from these nanoparticles (NPs) exhibited pH/reduction-responsive behaviors in vitro. These NPs interacted with the folate receptor overexpressed on the cell membrane of 4 T1 cells and achieved enhanced endocytosis. Afterwards, these NPs exhibited pH-responsiveness within endo-lysosomes and escaped from endosomes due to the “proton sponge” effect, and then completed release of DOX was triggered by high concentration of glutathione (GSH) in cytoplasm. Thus, DOX/FBH-NPs exhibited excellent cytotoxicity against 4 T1 cells in vitro. Benefited from the enhanced permeability and retention (EPR) effect and folate receptor-mediated endocytosis, these NPs gained satisfied tumor-targeting effects in vivo and efficient delivery of DOX to tumor tissues. As a result, these NPs exhibited enhanced antitumor effects and reduced side effects in vivo. In conclusion, these BSA-based NPs modified with both folate acid and histamine showed enhanced tumor-targeting effects in vivo with good biocompatibility and intracellular pH/reduction-responsive behaviors, providing a promising strategy for the efficient delivery of antitumor agents. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect