期刊
ACS NANO
卷 7, 期 8, 页码 6988-6996出版社
AMER CHEMICAL SOC
DOI: 10.1021/nn402199g
关键词
photodynamic therapy; photosensitizer; targeted delivery; ferritin; nanoparticle
类别
资金
- NCl/NIH [5R00CA153772, R01CA156775]
- UGA
- U.S. National Science Foundation [ECCS0823849, CBET 1139057]
- Georgia Cancer Coalition Distinguished Clinicians and Scientists Award
- Intramural Research Program of NIBIB
- NIH
- Major State Basic Research Development Program of China (973 Program) [2013CB733802]
- National Nature Science of Foundation of China (NSFC) [81101101, 51273165]
- Key Project of Chinese Ministry of Education [212149]
- NATIONAL CANCER INSTITUTE [R21CA120536, R00CA153772, R01CA156775] Funding Source: NIH RePORTER
Photodynamic therapy is an emerging treatment modality that is under, intensive preclinical and clinical investigations for many types of disease including cancer. Despite the promise, there is a lack of a reliable drug delivery vehicle that can transport photosensitizers (PSs) to tumors in a site-specific manner: Previous efforts have been focused on polymer- or liposome-based nanocarriers, which are usually associated with a suboptimal PS loading rate and a large particle size. We report herein that a RGD4C-modified ferritin (RFRT), a protein-based nanoparticle, can serve as a safe and efficient PS vehicle. Zinc hexadecafluorophthalocyanine (ZnF16Pc), a potent PS with a high 102 quantum yield but poor water solubility, can be encapsulated into RFRTs with a loading rate as high as similar to 60 wt % (i.e, 13 mg of ZnF16Pc can be loaded on 1 mg of RAM), which far exceeds those reported previously.. Despite the high loading, the ZnF16Pc-loaded Fans (P-RFRTs) show an overall particle size of 18.6 +/- 2.6 nm, which is significantly smaller than other PS-nanocarrier conjugates: When tested on U87MG subcutaneous tumor models, P-RFRTs showed a high tumor accumulation rate (tumor-to-normal tissue ratio of 26.82 +/- 4.07at 24 h), a good tumor inhibition rate (8164% on day 12), as well as minimal toxicity to the skin and other major organs. This technology can be extended to deliver other metal-containing PSs and holds great clinical translation potential.
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