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PorphyrinHDL: A Novel Photosensitizing Nanoparticle for Lung Cancer Therapy.
Annals of Thoracic Surgery 2018 October 12
BACKGROUND: We have developed ultra-small porphyrin-lipoprotein nanoparticles (<20nm) 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 towards development of a minimally-invasive treatment for peripheral lung cancer and metastatic lymph nodes of advanced lung cancer.
METHODS: The in vitro uptake of porphyrinHDL and the corresponding PDT efficacy were evaluated in both SR-BI positive and 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 H460 human lung cancer cell line. When irradiated with a 671 nm PDT laser, porphyrinHDL produced significant therapeutic effectiveness in vitro. After systemically 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%) with neither toxicity in normal tissues nor damage to adjacent critical structures.
CONCLUSIONS: SR-BI targeted porphyrinHDL-mediated PDT of lung cancer is selective and effective both in vitro and in vivo. These initial proof-of-principle studies suggest the potential of a "smart" PDT approach for highly selective tumor ablation.
METHODS: The in vitro uptake of porphyrinHDL and the corresponding PDT efficacy were evaluated in both SR-BI positive and 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 H460 human lung cancer cell line. When irradiated with a 671 nm PDT laser, porphyrinHDL produced significant therapeutic effectiveness in vitro. After systemically 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%) with neither toxicity in normal tissues nor damage to adjacent critical structures.
CONCLUSIONS: SR-BI targeted porphyrinHDL-mediated PDT of lung cancer is selective and effective both in vitro and in vivo. These initial proof-of-principle studies suggest the potential of a "smart" PDT approach for highly selective tumor ablation.
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