期刊
ACS APPLIED MATERIALS & INTERFACES
卷 8, 期 40, 页码 26630-26637出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.6b10255
关键词
Cerenkov radiation; photodynamic therapy; hollow mesoporous silica nanoparticles; chlorin e6; positron emission tomography
资金
- University of Wisconsin-Madison
- National Institutes of Health (NIBIB/NCI) [1R01CA169365, 1R01EB021336, P30CA014520]
- American Cancer Society [125246-RSG-13-099-01-CCE]
Traditional photodynamic therapy (PDT) requires external light to activate photosensitizers for therapeutic purposes. However, the limited tissue penetration of light is still a major challenge for this method. To overcome this limitation, we report an optimized system that uses Cerenkov radiation for PDT by using radionuclides to activate a well-known photosensitizer (chlorin e6, Ce6). By taking advantage of hollow mesoporous silica nanoparticles (HMSNs) that can intrinsically radiolabel an oxophilic zirconium-89 (Zr-89, t(1/2) = 78.4 h) radionuclide, as well as possess great drug loading capacity, Ce6 can be activated by Cerenkov radiation from Zr-89 in the same nanoconstruct. In-vitro cell viability experiments demonstrated dose-dependent cell deconstruction as a function of the concentration of Ce6 and Zr-89. In vivo studies show inhibition of tumor growth when mice were subcutaneously injected with [Zr-89]HMSN-Ce6, and histological analysis of the tumor section showed damage to tumor tissues, implying that reactive oxygen species mediated the destruction. This study offers a way to use an internal radiation source to achieve deep-seated tumor therapy without using any external light source for future applications.
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