Development of pH sensitive 2-(diisopropylamino)ethyl methacrylate based nanoparticlesfor photodynamic therapy

Abstract

Photodynamic therapy is an effective treatment for tumors that involves theadministration of light-activated photosensitizers. However, most photosensitizers areinsoluble and non-specific. To target the acid environment of tumor sites, wesynthesized three poly(ethylene glycol) methacrylate-co-2-(diisopropylamino)ethylmethacrylate (PEGMA-co-DPA) copolymers capable of self-assembly to form pHsensitive nanoparticles in an aqueous environment, as a means of encapsulating thewater-insoluble photosensitizer, meso-tetra(hydroxyphenyl)chlorin (m-THPC).The critical aggregation pH of the PEGMA-co-DPA polymers was 5.8–6.6 andthe critical aggregation concentration was 0.0045–0.0089 wt% at pH 7.4. Usingsolvent evaporation, m-THPC loaded nanoparticles were prepared with a highdrug encapsulation efficiency (approximately 89%). Dynamic light scattering andtransmission electron microscopy revealed the spherical shape and 132 nm diameter of thenanoparticles. The in vitro release rate of m-THPC at pH 5.0 was faster than at pH7.0 (58% versus 10% m-THPC released within 48 h, respectively). The in vitrophotodynamic therapy efficiency was tested with the HT-29 cell line. m-THPC loadedPEGMA-co-DPA nanoparticles exhibited obvious phototoxicity in HT-29 coloncancer cells after light irradiation. The results indicate that these pH sensitivenanoparticles are potential carriers for tumor targeting and photodynamic therapy.