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Photodynamic Therapy with Blended Conducting Polymer/Fullerene Nanoparticle Photosensitizers
Published on: October 28, 2015
Overcoming drug resistance with functional mesoporous titanium dioxide nanoparticles combining targeting, drug
Zhaoming Guo1, Kun Zheng, Zhenquan Tan
1School of Life Science and Medicine, Dalian University of Technology, Panjin, Liaoning 124221, China. guozm@dlut.edu.cn.
Abstract:
The resistance of tumor cells is a major cause of chemotherapy failure in cancer patients. Photodynamic therapy (PDT) as a noninvasive treatment strategy with high specificity is a promising method for the treatment of cancer. In this study, a CD44 and N-cadherin dual targeting drug delivery system in combination with mesoporous titanium dioxide nanoparticle (MTN)-based PDT has been successfully constructed for overcoming drug resistance. Hyaluronic acid (HA) and ADH-1 (a cyclic pentapeptide) were grafted onto the surface of MTN to construct ADH-1-HA-MTN, and doxorubicin (DOX) was selected as a model drug. HA can both trap DOX in the wells of MTN and target CD44-overexpressing tumor cells. ADH-1 blocks the EMT process of tumor cells by selectively inhibiting the function of N-cadherin. Besides, a large number of reactive oxygen species (ROS) were generated by MTN under X-ray irradiation, which could provide a cancer cell killing effect. Cytotoxicity tests showed that ADH-1-HA-MTN/DOX was more toxic to tumor cells than its non-ADH-1 modified counterparts. Western blotting analysis showed that ADH-1-HA-MTN/DOX overcame the drug resistance of tumor cells by preventing the process of epithelial-mesenchymal transition. Taken together, ADH-1-HA-MTN may be a promising targeted drug delivery system to overcome the drug resistance of tumors.
Insights
This study developed a dual-targeting drug delivery system using mesoporous titanium dioxide nanoparticles (MTN) to overcome tumor cell resistance to chemotherapy. The system targets CD44 and N-cadherin, enhancing treatment efficacy.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Tumor cell resistance to chemotherapy is a significant challenge in cancer treatment.
- Photodynamic therapy (PDT) offers a noninvasive, specific approach for cancer treatment.
Purpose of the Study:
- To construct a dual-targeting drug delivery system for overcoming drug resistance in cancer.
- To utilize mesoporous titanium dioxide nanoparticles (MTN) for targeted drug delivery and photodynamic therapy.
Main Methods:
- Grafting hyaluronic acid (HA) and ADH-1 peptide onto MTN to create ADH-1-HA-MTN.
- Loading doxorubicin (DOX) as a model drug into the MTN.
- Utilizing HA for CD44 targeting and ADH-1 for N-cadherin inhibition to block epithelial-mesenchymal transition (EMT).
- Employing X-ray irradiation to generate reactive oxygen species (ROS) from MTN for cancer cell killing.
Main Results:
- The ADH-1-HA-MTN/DOX system demonstrated enhanced cytotoxicity against tumor cells compared to controls.
- Western blotting confirmed that the system effectively prevented EMT, thereby overcoming drug resistance.
- MTN generated significant ROS under X-ray irradiation, contributing to the anti-cancer effect.
Conclusions:
- The developed ADH-1-HA-MTN system shows promise as a targeted drug delivery platform.
- This approach effectively overcomes tumor drug resistance by dual targeting and inhibiting EMT.
- The combination of drug delivery and PDT offers a potent strategy for cancer therapy.
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