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Overcoming drug resistance with functional mesoporous titanium dioxide nanoparticles combining targeting, drug delivery and photodynamic therapy

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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.

Graphical abstract: Overcoming drug resistance with functional mesoporous titanium dioxide nanoparticles combining targeting, drug delivery and photodynamic therapy

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Publication details

The article was received on 11 Jul 2018, accepted on 16 Oct 2018 and first published on 17 Oct 2018


Article type: Paper
DOI: 10.1039/C8TB01810C
Citation: J. Mater. Chem. B, 2018, Advance Article
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    Overcoming drug resistance with functional mesoporous titanium dioxide nanoparticles combining targeting, drug delivery and photodynamic therapy

    Z. Guo, K. Zheng, Z. Tan, Y. Liu, Z. Zhao, G. Zhu, K. Ma, C. Cui, L. Wang and T. Kang, J. Mater. Chem. B, 2018, Advance Article , DOI: 10.1039/C8TB01810C

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