Porphyrin–High-Density Lipoprotein: A Novel Photosensitizing Nanoparticle for Lung Cancer Therapy

Background We have developed ultrasmall porphyrin–high-density lipoprotein (HDL) nanoparticles ( Methods The in vitro uptake of porphyrinHDL and the corresponding PDT efficacy were evaluated in both SR-BI–positive and SR-BI–negative lung cancer cell lines. A clinically relevant orthotopic lung cancer model in mice was used to examine fluorescence activation and quantification of uptake in tumor. In addition, we investigated the effect of porphyrinHDL-mediated PDT. Results PorphyrinHDL promoted proper intracellular uptake in the H460 human lung cancer cell line. When irradiated with a 671-nm PDT laser, porphyrinHDL produced significant therapeutic effectiveness in vitro. After systemic administration in mice with orthotopic lung cancer xenografts, porphyrinHDL demonstrated selective accumulation and photoactivation in tumor with significantly enhanced disease-to-normal tissue contrast. Moreover, porphyrinHDL-PDT significantly induced cell apoptosis in lung tumors (73.2%) without toxicity in normal tissues or damage to adjacent critical structures. Conclusions SR-BI–targeted porphyrinHDL-mediated PDT of lung cancer is selective and effective in vitro and in vivo. These initial proof-of-principle studies suggest the potential of a "smart" PDT approach for highly selective tumor ablation.