Photodynamic therapy (PDT) is an emerging treatment modality that is under intensive preclinical and clinical investigations for treatments of many diseases including cancer. For the purposes, it is paramount to develop a reliable drug delivery vehicle that can deliver photosensitizers (PSs) to tumors in a site-specific manner. Previous efforts have been focused on polymer- and liposome-based nanocarriers, which are usually associated with a suboptimal PS loading rate and a large particle size. Recently, we found that ferritin (FRT) nanocages can be conjugated with targeting motifs, such as RGD4C and folic acid, and serve as a safe and efficient PS carrier. In particular, we found that zinc hexadecafluorophthalocyanine (ZnF16Pc), a potent PS with a high 1O2 quantum yield (0.85 in THF) but poor water solubility, can be encapsulated into FRTs at a high loading rate (up to ~60 wt %) without comprising the colloidal stability of the nanoparticles (hydrodynamic size of the conjugates is ~8.6 ± 2.6 nm). When tested in murine U87MG subcutaneous tumor models, ZnF16Pc-loaded and RGD4C-modified FRTs (P-RFRTs) showed high tumor selectivity (tumor-to-normal-tissue ratio of 26.82 ± 4.07 at 24 h), excellent tumor control under photoirradiation (tumor growth inhibition, or TGI, rate of 83.64% on day 12), and low toxicity to the skin as well as major organs. When tested in 4T1 tumor bearing BALB/c mice, ZnF16Pc-loaded and folic acid conjugated FRTs (P-FA-FRTs) efficiently suppressed not only primary tumor growth (TGI rate of 82.65% on day 14) but also tumor metastasis to the lung, which is attributable to a PDT-stimulated anti-tumor immune response. The technology can be extended to deliver other PSs or chemotherapeutics to tumors and holds great potential in clinical translation.

Tumor targeted ferritin nanocages for efficient photodynamic therapy

251st National Meeting (2016)

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