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

Abstract

Photodynamic therapy is an effective treatment for tumors that involves the administration of light-activated photosensitizers. However, most photosensitizers are insoluble and non-specific. To target the acid environment of tumor sites, we synthesized three poly(ethylene glycol) methacrylate-co-2-(diisopropylamino)ethyl methacrylate (PEGMA-co-DPA) copolymers capable of self-assembly to form pH sensitive nanoparticles in an aqueous environment, as a means of encapsulating the water-insoluble photosensitizer, meso-tetra(hydroxyphenyl)chlorin (m-THPC). The critical aggregation pH of the PEGMA-co-DPA polymers was 5.8-6.6 and the critical aggregation concentration was 0.0045-0.0089 wt% at pH 7.4. Using solvent evaporation, m-THPC loaded nanoparticles were prepared with a high drug encapsulation efficiency (approximately 89%). Dynamic light scattering and transmission electron microscopy revealed the spherical shape and 132 nm diameter of the nanoparticles. The in vitro release rate of m-THPC at pH 5.0 was faster than at pH 7.0 (58% versus 10% m-THPC released within 48 h, respectively). The in vitro photodynamic therapy efficiency was tested with the HT-29 cell line. m-THPC loaded PEGMA-co-DPA nanoparticles exhibited obvious phototoxicity in HT-29 colon cancer cells after light irradiation. The results indicate that these pH sensitive nanoparticles are potential carriers for tumor targeting and photodynamic therapy.

Photoinduced effects of m-tetrahydroxyphenylchlorin loaded lipid nanoemulsions on multicellular tumor spheroids

“…liposomal mTHPC formulations [28, 29] or the encapsulation of mTHPC into nanoparticles composed of poly(lactic-co-glycolic acid) [30], poly(lactic-co-glycolic acid)-b-poly(ethylene glycol) [31], poly(ethylene glycol) methacrylate-co-2-(diisopropylamino)ethyl methacrylate copolymers [32], human serum albumin [33], organic-modified silica [34] or calcium phosphate. [35] These studies describe promising carriers for mTHPC by improving solubility and reducing dark toxicity however it is not possible to directly compare them as very different model systems were used in each case.…”

pH-sensitive drug-delivery Systems for Tumor Targeting

“…When the pH became slightly acidic, polyHis became charged and exposed pH e triggered tumor targeting via ionization mechanism Various ionizable monomers could be employed as materials for pH-sensitive micelles, including sulfonates [26], carboxylic acids [27] and amines [28]. 2-(disopropylamino) ethyl methacrylate (DPA) is an amine-containing monomer, which is highly biocompatible and pH sensitive with a pKa of 6.2 [41,42]. At physiological pH, DPA is hydrophobic due to its deionization, however, at pH e , it could be ionized and becomes hydrophilic.…”

“…At physiological pH, DPA is hydrophobic due to its deionization, however, at pH e , it could be ionized and becomes hydrophilic. Peng et al synthesized PEG methacrylate-co-DPA (PEGMA-co-DPA) by free radical polymerization [42]. The copolymer can selfassemble into NPs encapsulating hydrophobic photosensitizer, meso-tetra(hydroxyphenyl) chlorin (m-THPC).…”

Tumor Ablation and Nanotechnology

“…A wide range of nanoparticles are being used as vehicles for photosensitizers including polymeric nanoparticles, liposomes, silica, and gold nanoparticles 116-120. In addition to protecting the healthy tissue from potential cytotoxicity from the photosensitizers, nanoparticles prevent the photosensitizer from leaking, minimizing degradation and consequent inactivity of the photosensitizer in the biological environment.…”