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| Content Provider | Royal Society of Chemistry (RSC) |
|---|---|
| Author | Jiang, Wenting Fang, Xueyang Huang, Yanyu Yang, Fang Chen, Tianfeng |
| Copyright Year | 2017 |
| Abstract | Multidrug resistance is one of the main causes leading to failure of chemotherapy. Therefore, the rational design of targeting drug systems to reverse multidrug resistance is becoming an important strategy for cancer therapy. Herein, we present a novel copolymer-based nanoparticle that was size changeable and could realize the goal of precise drug controlled release under acidic conditions, and could overcome the multidrug resistance in breast cancer cells. This PCP/uPA nanosystem was formed through the crosslinking between chitosan (CS) and poly(N-isopropylacrylamide) (PNIPAM), followed by surface decoration with polyethylene glycol (mPEG) and a breast cancer targeting peptide uPA, which was then used to encapsulate metal complexes (RuPOP and Fe(PiP)3) to solve their bottleneck of low solubility and stability under physiological conditions. These multifunctional nanosystems (PCP-Ru/uPA and PCP-Fe/uPA) exhibited remarkable anticancer activity and could overcome the poor stability and low solubility of RuPOP and Fe(PiP)3. Noticeably, PCP-Ru/uPA reversed the multidrug resistance of drug-resistant MCF-7 (MCF-7R) human breast cancer cells by enhancing the cellular uptake of RuPOP by MCF-7R cells and inhibiting the expression of ABC family proteins. Furthermore, when PCP-Ru/uPA was at pH 5.3 with lysozyme, the release amount of RuPOP is the largest compared with pH at 5.3 or 7.4, and the release rate of RuPOP reached 75% at 48 h. In other words, the nanosystem with a pH-responsive effect swelled in an acidic environment and released free RuPOP in the lysosome of cancer cells efficiently, which triggered ROS up-regulation and induced apoptosis in MCF-7R cells. Taken together, this study presents a novel size changeable nanosystem for precise drug controlled release and efficient overcoming of cancer multidrug resistance. |
| Starting Page | 944 |
| Ending Page | 952 |
| Page Count | 9 |
| File Format | HTM / HTML PDF |
| ISSN | 2050750X |
| Volume Number | 5 |
| Issue Number | 5 |
| Journal | Journal of Materials Chemistry B |
| DOI | 10.1039/c6tb02361d |
| Language | English |
| Publisher | Royal Society of Chemistry |
| Access Restriction | Open |
| Subject Keyword | ABC Multiple drug resistance Chemotherapy Cancer Nanoparticle Breast cancer Chitosan Poly(N-isopropylacrylamide) Polyethylene glycol Signal peptide Nanotechnology MCF-7 American Broadcasting Company PH Lysozyme Lysosome Reactive oxygen species Apoptosis |
| Content Type | Text |
| Resource Type | Article |
| Subject | Chemistry Medicine Materials Science Biomedical Engineering |
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