Multifunctional Mesoporous Silica Nanoparticles for Targeted Delivery, Chemotherapy, and Photodynamic Therapy

Project: Research

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Description

Combination therapy involves the use of two or more treatment modalities or drugs together. It has shown higher therapeutic efficacy when compared with the individual therapeutic methods, particularly in suppressing drug resistance and preventing disease recurrence. Recently, combined chemotherapy and photodynamic therapy (PDT) has received considerable attention as a promising way to treat cancer. PDT utilizes the combined action of a photosensitizer, light, and molecular oxygen to generate reactive oxygen species to eradicate tumor cells. It is generally non-invasive and can tolerate repeated doses. The cytotoxic effect can be induced specifically at the malignant site through precise delivery of the light. In chemotherapy, targeted delivery of anticancer drugs remains as a major challenge. Functional nanoparticles have found to be excellent carriers which can prolong the half-life of the drugs, improve their water solubility, reduce the immunogenicity, and enhance their localization at the tumor site by either passive or active targeting. To further reduce the toxic side effects of the drugs, it is desirable that they can be released in a controlled manner. As a result, development of nanocarriers that can deliver anticancer drugs specifically to the tumor site and control their release through interactions with some tumor-associated stimuli is of great importance. The aim of this project is to develop multifunctional nanocarriers based on mesoporous silica nanoparticles (MSN) for photosensitizers and anticancer drugs with a view to achieving synergistic cytotoxic effects. We plan to prepare a series of multifunctional MSN which encapsulate conjugates of pyropheophorbide a (Pyro) and doxorubicin linked with an acid-labile hydrazone bond. The outer surface of the MSN will also be decorated with folate groups to target the folate receptors overexpressed in tumor cells. On the basis that the extracellular region of solid tumors and some intracellular compartments are acidic, the hydrazone linkage is expected to be cleaved favorably in these regions to release the doxorubicin. Upon irradiation, the Pyro moiety, which is still covalently linked to MSN, will trigger the formation of singlet oxygen, which also causes cellular and tissue damage. Hence, the resulting multifunctional MSN can offer several levels of control of the drug specificity and afford synergistic anticancer effects. Apart from the synthesis and study of the acid-triggered release of doxorubicin, the in vitro and in vivo photodynamic activities of these nanosystems will also be examined and compared with those of some reference compounds.

Detail(s)

Project number9042161
Grant typeGRF
StatusFinished
Effective start/end date1/01/1326/06/17