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

Abstract

We have developed ultrasmall porphyrin-high-density lipoprotein (HDL) nanoparticles (<20 nm), called "porphyrinHDL," that have a high density of porphyrin molecules and dissociate rapidly upon tumor cell accumulation to become fluorescent and photoactive. This is introduced as a novel activatable photosensitizer for image-guided photodynamic therapy (PDT). Here, we report the studies of these nanoparticles targeted to scavenger receptor class B type I (SR-BI) expressed on lung cancer cells as a first step toward development of a minimally invasive treatment for peripheral lung cancer and metastatic lymph nodes of advanced lung cancer. The invitro 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. 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 invitro. 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. SR-BI-targeted porphyrinHDL-mediated PDT of lung cancer is selective and effective invitro and invivo. These initial proof-of-principle studies suggest the potential of a "smart" PDT approach for highly selective tumor ablation.