期刊
MOLECULAR PHARMACEUTICS
卷 15, 期 8, 页码 3595-3599出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.8b00419
关键词
fibroblast activation protein; cancer-associated fibroblast; photodynamic therapy; single chain viable fragment; ferritin; tumor penetration
资金
- National Natural Science Foundation of China (NSFC) [81771869, 81571708, 81501506]
- Technology Department of Jilin Province [20160101001JC]
- Norman Bethune Program of Jilin University [2015219]
- National Institutes of Health [R01EB022596, R01NS093314]
- Congressionally Directed Medical Research Program [CA140666]
- National Science Foundation [NSF1552617]
- CDMRP [CA140666, 793849] Funding Source: Federal RePORTER
Nanoparticles have been widely tested as drug delivery carriers or imaging agents, largely because of their ability to selectively accumulate in tumors through the enhanced permeability and retention (EPR) effect. However, studies show that many tumors afford a less efficient EPR effect and that many nanoparticles are trapped in the perivascular region after extravasation and barely migrate into tumor centers. This is to a large degree attributed to the dense tumor extracellular matrix (ECM), which functions as a physical barrier to prevent efficient nanoparticle extravasation and diffusion. In this study, we report a photodynamic therapy (PDT) approach to enhance tumor uptake of nanoparticles. Briefly, we encapsulate ZnF16Pc, a photosensitizer, into ferritin nanocages, and then conjugate to the surface of the ferritin a single chain viable fragment (scFv) sequence specific to fibroblast activation protein (FAP). FAP is a plasma surface protein widely upregulated in cancer associated fibroblasts (CAFs), which is a major source of the ECM fiber components. We found that the scFv-conjugated and ZnF16Pc-loaded ferritin nanoparticles (scFv-Z@FRT) can mediate efficient and selective PDT, leading to eradication of CAFs in tumors. When tested in bilateral 4T1 tumor models, we found that the tumor accumulation of serum albumin (BSA), 10 nm quantum dots (QDs), and 50 nm QDs was increased by 2-, 3.5-, and 18-fold after scFv-Z@FRT mediated PDT. Our studies suggest a novel and safe method to enhance the delivery of nanoparticles to tumors.
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