Size-engineered biocompatible polymeric nanophotosensitizer for locoregional photodynamic therapy of cancer.
Current approaches in use of water-insoluble photosensitizers for photodynamic therapy (PDT) of cancer often demand a nano-delivery system. Here, we report a photosensitizer-loaded biocompatible nano-delivery formulation (PPaN-20) whose size was engineered to ca. 20nm to offer improved cell/tissue penetration and efficient generation of cytotoxic singlet oxygen. PPaN-20 was fabricated through the physical assembly of all biocompatible constituents: pyropheophorbide-a (PPa, water-insoluble photosensitizer), polycaprolactone (PCL, hydrophobic/biodegradable polymer), and Pluronic F-68 (clinically approved polymeric surfactant). Repeated microemulsification/evaporation method resulted in a fine colloidal dispersion of PPaN-20 in water, where the particulate PCL matrix containing well-dispersed PPa molecules inside was stabilized by the Pluronic corona. Compared to a control sample of large-sized nanoparticles (PPaN-200) prepared by a conventional solvent displacement method, PPaN-20 revealed optimal singlet oxygen generation and efficient cellular uptake by virtue of the suitably engineered size and constitution, leading to high in vitro phototoxicity against cancer cells. Upon administration to tumor-bearing mice by peritumoral route, PPaN-20 showed efficient tumor accumulation by the enhanced cell/tissue penetration evidenced by in vivo near-infrared fluorescence imaging. The in vivo PDT treatment with peritumorally administrated PPaN-20 showed significantly enhanced suppression of tumor growth compared to the control group, demonstrating great potential as a biocompatible photosensitizing agent for locoregional PDT treatment of cancer.
Center for Theragnosis, Korea Institute of Science and Technology, 39-1Hawolgok-dong, Seongbuk-gu, Seoul 136-791, South Korea; Carbon Nanomaterials Design Laboratory, Global Research Laboratory, Research Institute of Advanced Materials, and Department of Materials Science and Engineering, Seoul National University, Gwanak-gu, Seoul 151-744, South Korea.
Keunsoo
K
Jeong
Center for Theragnosis, Korea Institute of Science and Technology, 39-1Hawolgok-dong, Seongbuk-gu, Seoul 136-791, South Korea; Department of Chemistry, Kyung Hee University, Dongdaemoon-gu, Seoul 130-701, South Korea.
Solji
S
Park
Center for Theragnosis, Korea Institute of Science and Technology, 39-1Hawolgok-dong, Seongbuk-gu, Seoul 136-791, South Korea.
Yong-Deok
YD
Lee
Center for Theragnosis, Korea Institute of Science and Technology, 39-1Hawolgok-dong, Seongbuk-gu, Seoul 136-791, South Korea.
Chi Soo
CS
Kang
Department of Chemistry, Kyung Hee University, Dongdaemoon-gu, Seoul 130-701, South Korea.
Hyun Jun
HJ
Kim
Department of Chemistry, Kyung Hee University, Dongdaemoon-gu, Seoul 130-701, South Korea.
Hyeonjong
H
Park
Center for Theragnosis, Korea Institute of Science and Technology, 39-1Hawolgok-dong, Seongbuk-gu, Seoul 136-791, South Korea.
Ick Chan
IC
Kwon
Department of Chemistry, Kyung Hee University, Dongdaemoon-gu, Seoul 130-701, South Korea.
Jungahn
J
Kim
Carbon Nanomaterials Design Laboratory, Global Research Laboratory, Research Institute of Advanced Materials, and Department of Materials Science and Engineering, Seoul National University, Gwanak-gu, Seoul 151-744, South Korea.
Chong Rae
CR
Park
Center for Theragnosis, Korea Institute of Science and Technology, 39-1Hawolgok-dong, Seongbuk-gu, Seoul 136-791, South Korea. Electronic address: sehoonkim@kist.re.kr.
Sehoon
S
Kim
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D002734:Chlorophyll / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D016503:Drug Delivery Systems; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D036103:Nanotechnology / Q000379:methods*; D009369:Neoplasms / Q000188:drug therapy*; D010316:Particle Size; D038761:Photobleaching / Q000187:drug effects; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011091:Polyesters / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D026082:Singlet Oxygen / Q000737:chemistry
D001672:Biocompatible Materials; D017319:Photosensitizing Agents; D011091:Polyesters; D011108:Polymers; D002734:Chlorophyll; D026082:Singlet Oxygen; C040298:pyropheophorbide a; C016240:polycaprolactone
Photodynamic therapy; Physical assembly; Pluronic polymer nanoparticle; Polycaprolactone; Pyropheophorbide-a