Shifting the absorption to the near-infrared region and inducing a strong photothermal effect by encapsulating zinc(II) phthalocyanine in poly(lactic-co-glycolic acid)-hyaluronic acid nanoparticles

Abstract

By using an oil-in-water single emulsion method, a series of multifunctional hybrid nanoparticles (NPs) were prepared which consisted of a core of poly(lactic-co-glycolic acid) (PLGA) with a lipoid shell of n-hexadecylamine-substituted hyaluronic acid (HA), encapsulating a zinc(II) phthalocyanine-based photosensitizer (ZnPc). As determined by laser light scattering, these hybrid NPs labeled as ZnPc@PLGA-HA NPs possessed a hydrodynamic diameter of 280 nm and a surface charge of -30 mV, showing high stability in serum. The Q-band absorption of ZnPc exhibited a large red-shift from 674 nm for free ZnPc in dimethylsulfoxide to 832 nm for this nanosystem in water. Upon light irradiation at 808 nm, the encapsulated ZnPc induced a strong photothermal effect instead of photodynamic action, which is usually observed for ZnPc-containing NPs. The tumor-targeting effect of these NPs due to the HA coating was investigated against the human colorectal adenocarcinoma HT29 cells and human lung carcinoma A549 cells, both of which overexpress cluster determinant 44 (CD44) receptors, using the CD44-negative human normal hepatic LO2 cells as a negative control. The photothermal cell-killing effect of these NPs was significantly higher for the two CD44-positive cell lines than that for the negative control. Their in vivo photothermal efficacy was also examined on HT29 tumor-bearing nude mice. Upon irradiation, the NPs caused significant temperature increase at the tumor site and ablation of the tumor. The results showed that these multifunctional NPs could serve as an effective photothermal agent for targeted photothermal therapy. Statement of significance Phthalocyanines are well-known photosensitizers for photodynamic therapy. By encapsulating these molecules into various nanoplatforms, a range of multifunctional photosensitizing systems have been developed for cancer therapy. In this study, we have demonstrated that by careful selection of phthalocyanines and the nanocarriers, as well as the self-assembly and encapsulation methods, the encapsulated phthalocyanine molecules could switch the photoinduced action from photodynamic therapy to photothermal therapy as a result of the enhanced aggregation of the macrocyclic molecules in the nanoparticles. The unique packing of the molecules also resulted in a large red-shift of the Q-band absorption to 832 nm, facilitating the in vitro and in vivo photothermal treatment.

Keywords: PLGA nanoparticles; Photodynamic therapy; Photosensitizer; Photothermal therapy; Phthalocyanine.