title: Self-assembled photosensitizer-conjugated nanoparticles for targeted photodynamic therapy.
abstract: An effective tumor-targeted drug delivery system for photodynamic therapy was developed by designing ligand-mediated nanoparticles with stable formulations of a hydrophobic photosensitizer. Novel folic acid (FA)-conjugated amphiphilic block copolymers of polyethylene glycol (PEG) and poly-β-benzyl-L-aspartate (PBLA) with the potential to act as pH-responsive drug release reservoirs were synthesized. The photosensitizer, 2,4-diacetyl deuteroporphyrin IX dimethyl ether (DD-PpIX), was conjugated to the copolymers through pH-sensitive hydrazone linkage. The syntheses and compositions of all copolymers were confirmed by ¹H NMR measurement. Photosensitizer-conjugated amphiphilic copolymeric nanoparticles (FA-PEG-P(Asp-Hyd)-DD-PpIX) were prepared by micelle formation in aqueous solution. The particle sizes of the FA-PEG-PBLA and FA-PEG-P(Asp-Hyd)-DD-PpIX nanoparticles were determined by light-scattering measurements. The range was 105-298 nm, depending on copolymer molecular weight and composition. Field emission scanning electron microscopy showed that the FA-PEG-P(Asp-Hyd)-DD-PpIX copolymeric nanoparticles were submicron in size and spherical in shape. The results of in vitro release tests showed that the release profiles of DD-PpIX from the nanoparticles were strongly pH-dependent and influenced by the amount of photosensitizer that was conjugated. In vitro tests using HeLa cells indicated that the FA-PEG-P(Asp-Hyd)-DD-PpIX nanoparticles had low dark-toxicity and showed more than 97% of cellular uptake. Based on our results, the FA-PEG-P(Asp-Hyd)-DD-PpIX nanoparticle system could be a promising approach for developing novel photosensitizer delivery carriers for photodynamic therapy.
authors.affiliation: Graduate School of Green Energy Technology, Chungnam National University, South Korea.
authors.forename: Linlin
authors.initials: L
authors.lastname: Zhao
authors.forename: Tae-Hyun
authors.initials: TH
authors.lastname: Kim
authors.forename: Kang Moo
authors.initials: KM
authors.lastname: Huh
authors.forename: Hae-Won
authors.initials: HW
authors.lastname: Kim
authors.forename: So Yeon
authors.initials: SY
authors.lastname: Kim
mesh_terms: D006367:HeLa Cells; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D053758:Nanoparticles; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage*
chemical_list: D008823:Micelles; D017319:Photosensitizing Agents