A self-assembled pH/enzyme dual-responsive prodrug with PEG deshielding for multidrug-resistant tumor therapy
| Autor: | Yun Chen, Zhiyuan Xu, Ronghua Ni, Jianhua Zhu |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Surface Properties
Biomedical Engineering Mice Nude ATP-binding cassette transporter 02 engineering and technology 010402 general chemistry Endocytosis 01 natural sciences Polyethylene Glycols Rats Sprague-Dawley Mice In vivo Cell Line Tumor PEG ratio Animals Humans General Materials Science Prodrugs Particle Size Cell Proliferation Antibiotics Antineoplastic Molecular Structure Chemistry Mammary Neoplasms Experimental General Chemistry General Medicine Prodrug Hydrogen-Ion Concentration 021001 nanoscience & nanotechnology Drug Resistance Multiple 0104 chemical sciences Rats Multiple drug resistance Drug Liberation Doxorubicin Drug Resistance Neoplasm Cancer research PEGylation MCF-7 Cells Matrix Metalloproteinase 2 Nanoparticles ATP-Binding Cassette Transporters Efflux Drug Screening Assays Antitumor 0210 nano-technology Peptides |
| Zdroj: | Journal of materials chemistry. B. 8(6) |
| ISSN: | 2050-7518 |
| Popis: | Multidrug resistance (MDR) is one of the major obstacles for tumor therapy. Intake by receptor-mediated endocytosis enables molecules to bypass ABC transporter efflux, which is the primary mechanism of MDR. Here, we developed a novel pH/enzyme dual-responsive polypeptide prodrug to reverse multidrug resistance. This drug is composed of pH/MMP2-sensitive nanoparticles (MSNPs) self-assembled from mPEG–peptide–DOX. MSNPs can overcome sequential physiological barriers of multidrug resistance by prolonging the circulation time through PEGylation, enhancing tumor accumulation through passive targeting, increasing tumor penetration by enzyme-sensitive PEG deshielding, bypassing ABC transporter efflux by undergoing receptor-mediated endocytosis, and inducing sufficient DOX release from nanoparticles triggered by lysosomal pH. The reversal of MDR by MSNPs was evaluated in MCF-7/ADR cells and nude mice bearing tumors consisting of MCF-7/ADR cells. Both in vitro and in vivo studies showed that the MSNPs can effectively reverse MDR. Thus, MSNPs may constitute a potentially promising strategy for overcoming MDR in clinical applications. |
| Databáze: | OpenAIRE |
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