期刊
ADVANCED FUNCTIONAL MATERIALS
卷 25, 期 23, 页码 3472-3482出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adfm.201500737
关键词
gene delivery; photochemical internalization (PCI); photosensitizer; pH-responsive materials; tumor therapy
类别
资金
- Strategic Research through the National Research Foundation of Korea (NRF) - Korea government (MSIP) [2011-0028726]
- National Research Foundation of Korea [21A20132112043] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Gene therapy has great potential to bring tremendous improvement to cancer therapy. Recently, photochemical internalization (PCI) has provided the opportunity to overcome endo-lysosomal sequestration, which is one of the main bottlenecks in both gene and chemotherapeutic delivery. Despite PCI having shown great potential in gene delivery systems, it still remains difficult to perform due to the photo-oxidation of exogenous cargo genes by reactive oxygen species (ROS) generated from activated photosensitizers (PSs). In this paper, a new type of a stable light-triggered gene delivery system is demonstrated based on endo-lysosomal pH-responsive polymeric PSs, which serve as shielding material for the polymer/gene complex. By taking advantage of the endo-lysosomal pH-sensitive de-shielding ability of the pH-responsive shielding material incorporated in the ternary gene complexes (pH-TCs), a more significant photo-triggered gene expression effect is achieved without damage to the gene from ROS. In contrast, pH-insensitive material-shielded nanocarriers cause photo-oxidation of the payload and do not generate a notable transfection efficacy. Importantly, with the benefit of our newly developed gene delivery system, the deep penetration issue can be resolved. Finally, the light-triggered gene delivery system using pH-TCs is applied to deliver the therapeutic p53 gene in melanoma K-1735 bearing mice, showing excellent therapeutic potential for cancer.
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