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.

Gold nanorod‐photosensitizer conjugates with glutathione‐sensitive linkages for synergistic cancer photodynamic/photothermal therapy

“…The synthesis of FA‐conjugated block copolymers was based on the previous study by Zhao, Kim, Ahn, et al () and Zhao, Kim, Huh, Kim, and Kim (). First, FA‐PEG‐NH 2 was synthesized through the reaction between the amino group of PEG‐bis(amine) and the carboxyl group of FA.…”

Photodynamic nanomedicine in the treatment of solid tumors: Perspectives and challenges

“…For example, Yin et al conjugated the AS1411 aptamer to multifunctional iron oxide nanoparticles packaging 5,10,15,20-tetrakis(1-methylpyridinium-4-yl) porphyrin (TMPyP4) for multimodal imaging and subsequent PDT of breast cancer [34]. Other examples where porphyrin PS have been packaged in nanoparticles capable of active targeting of cancer cells include mannose receptor-targeted silica nanoparticles, CD22-targeted viral nanoparticles and folate receptor-targeted polymeric nanoparticles [39, 40, 44, 54]. …”

Photodynamic Therapy: One Step Ahead with Self-Assembled Nanoparticles

“…108 In an attempt to improve tumor-targeted drug delivery system in PDT, folic acid (FA)-conjugated amphiphilic block copolymers of PEG and poly-β-benzyl- L -aspartate (PBLA) were synthesized with the potential to act as pH-responsive PS release reservoirs. 109 2,4-Diacetyl deuteroporphyrin IX dimethyl ether (DD-PpIX) was conjugated to amphiphilic copolymeric nanoparticles (to produce FA-PEG-P(Asp-Hyd)-DD-PpIX) which formed micelles in aqueous solution. In vitro release tests demonstrated strong pH dependence 107 and more than 97% cellular uptake have been achieved using HeLa cells.…”

“…In vitro release tests demonstrated strong pH dependence 107 and more than 97% cellular uptake have been achieved using HeLa cells. 109 …”