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Novel ZnO hollow-nanocarriers containing paclitaxel targeting folate-receptors in a malignant pH-microenvironment for effective monitoring and promoting breast tumor regression
| Content Provider | PubMed Central |
|---|---|
| Author | Puvvada, Nagaprasad Rajput, Shashi Kumar, B. N. Prashanth Sarkar, Siddik Konar, Suraj Brunt, Keith R. Rao, Raj R. Mazumdar, Abhijit Das, Swadesh K. Basu, Ranadhir Fisher, Paul B. Mandal, Mahitosh Pathak, Amita |
| Copyright Year | 2015 |
| Abstract | Low pH in the tumor micromilieu is a recognized pathological feature of cancer. This attribute of cancerous cells has been targeted herein for the controlled release of chemotherapeutics at the tumour site, while sparing healthy tissues. To this end, pH-sensitive, hollow ZnO-nanocarriers loaded with paclitaxel were synthesized and their efficacy studied in breast cancer in vitro and in vivo. The nanocarriers were surface functionalized with folate using click-chemistry to improve targeted uptake by the malignant cells that over-express folate-receptors. The nanocarriers released ~75% of the paclitaxel payload within six hours in acidic pH, which was accompanied by switching of fluorescence from blue to green and a 10-fold increase in the fluorescence intensity. The fluorescence-switching phenomenon is due to structural collapse of the nanocarriers in the endolysosome. Energy dispersion X-ray mapping and whole animal fluorescent imaging studies were carried out to show that combined pH and folate-receptor targeting reduces off-target accumulation of the nanocarriers. Further, a dual cell-specific and pH-sensitive nanocarrier greatly improved the efficacy of paclitaxel to regress subcutaneous tumors in vivo. These nanocarriers could improve chemotherapy tolerance and increase anti-tumor efficacy, while also providing a novel diagnostic read-out through fluorescent switching that is proportional to drug release in malignant tissues. |
| Related Links | http://dx.doi.org/10.1038/srep11760 |
| Starting Page | 11760 |
| File Format | |
| ISSN | 20452322 |
| e-ISSN | 20452322 |
| Journal | Scientific Reports |
| Volume Number | 5 |
| Language | English |
| Publisher | Nature Publishing Group |
| Access Restriction | Open |
| Rights Holder | Nature Publishing Group |
| Subject Keyword | Science and technology Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
