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Polychloromethylstyrene (PCMS)-block-polystyrene (PS) copolymers were prepared by controlled free-radical polymerization in the presence of 2,2,6,6-tetramethylpiperidinooxy and 2,2′-azobisisobutyronitrile (AIBN) initiator. The PCMS-b-PS copolymers had narrow molecular weight distributions, and the block lengths were controlled by the reaction time and the molar ratios of chloromethylstyrene/AIBN and styrene/PCMS macroinitiator. The block copolymers were further quaternized with triethylamine. The amphiphilic cationic block copolymers formed colloidal particles; the effects of the pH value, salt concentration, and solvent polarity on the particle size were investigated with a dynamic light scattering analyzer. The average colloid size increased with increasing pH value and salt concentration. This implied that the colloid formed a protonated hydrophilic shell and hydrophobic styrene core in water. Furthermore, with the addition of tetrahydrofuran to the aqueous solution, the styrene segments in the core could be inverted to the outside of the colloid. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013

Photodynamic therapy (PDT) is a light-induced chemical reaction that produces localized tissue damage for the treatment of cancers and various nonmalignant conditions. In the clinic, patients treated with PDT should be kept away from direct sunlight or strong indoor lighting to avoid skin phototoxicity. In a previous study, it was demonstrated that the skin phototoxicity of meta-tetra(hydroxyphenyl)chlorin (m-THPC), a photosensitizer used in the clinic, can be significantly reduced after micellar encapsulation; however, no improvement in antitumor efficacy was observed. In this work, a folate-conjugated polymeric m-THPC delivery system is developed for improving tumor targeting of the photosensitizer, preventing photodamage to the healthy tissue, and increasing the effectiveness of the photosensitizers. The results demonstrate that folate-conjugated m-THPC-loaded micelles with particle sizes around 100 nm are taken up and accumulated by folate receptor-overexpressed KB cells in vitro and in vivo, and their PDT has no significant adverse effects on the body weight of mice. After an extended delivery time, a single dose of folate-conjugated m-THPC-loaded micelles has higher antitumor effects (tumor growth inhibition = 92%) through inhibition of cell proliferation and reduction of vessel density than free m-THPC or m-THPC-loaded micelles at an equivalent m-THPC concentration of 0.3 mg kg(-1) after irradiation. Furthermore, folate-conjugated m-THPC-loaded micelles at only 0.2 mg kg(-1) m-THPC have a similar antitumor efficacy to m-THPC or m-THPC-loaded micelles with the m-THPC concentration at 0.3 mg kg(-1) , which indicates that the folate conjugation on the micellar photosensitizer apparently reduces the requirement of m-THPC for PDT. Thus, folate-conjugated m-THPC-loaded micelles with improved selectivity via folate-folate receptor interactions have the potential to reduce, not only the skin photosensitivity, but also the drug dose requirement for clinical PDT.