Poly(styrene-co-maleic acid) Micelle of Photosensitizers for Targeted Photodynamic Therapy, Exhibits Prolonged Singlet Oxygen Generating Capacity and Superior Intracellular Uptake

Author:

Bharate Gahininath YadavraoORCID,Qin Haibo,Fang Jun

Abstract

Targeted therapy by using nanomedicines based on the enhanced permeability and retention (EPR) effect is becoming a promising anticancer strategy. Many nano-designed photosensitizers (PSs) for photodynamic therapy (PDT) have been developed which show superior therapeutic potentials than free PS. To further understand the advantages of nano-designed PS, in this study, we used styrene-co-maleyl telomer (SMA) as a polymer platform to prepare a micellar type of PS with two well-characterized PSs—rose bengal (RB) and methylene blue (MB)—and evaluated the outmatching benefits of SMA-PS micelles, especially focusing on the singlet oxygen (1O2) generation capacity and intracellular uptake profiles. In aqueous solutions, SMA-PS self-assembles to form micelles by non-covalent interactions between PS and SMA. SMA-PS micelles showed discrete distributions by dynamic light scattering having a mean particle size of 18–30 nm depending on the types of SMA and different PSs. The hydrodynamic size of SMA-PS was evaluated by Sephadex chromatography and it found to be 30–50 kDa. In the presence of human serum albumin, the sizes of SMA-PS remarkably increased, suggesting the albumin-binding property. 1O2 generation from the SMA-PS micelle was determined by electron spin resonance, in which the SMA-PS micelle showed comparatively more photo-stable, and consequently a more durable and constant, 1O2 generation capability than free PS. Moreover, intracellular uptake of SMA-PS micelles was extensively faster and higher than free PS, especially in tumor cells. Taken together, SMA-PS micelles appear highly advantageous for photodynamic therapy in addition to its capacity in utilizing the EPR effect for tumor targeted delivery.

Funder

Japan Society for the Promotion of Science

Publisher

MDPI AG

Subject

Medicine (miscellaneous)

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