Abstract
Photodynamic therapy (PDT) has emerged as a potent novel therapeutic modality that induces cell death through light-induced activation of photosensitizer. But some photosensitizers have characteristics of poor water-solubility and non-specific tissue distribution. These characteristics become main obstacles of PDT. In this paper, we synthesized a targeting drug delivery system (TDDS) to improve the water-solubility of photosensitizer and enhance the ability of targeted TFR positive tumor cells. TDDS is a transferrin-modified Poly(D,L-Lactide-co-glycolide (PLGA) and carboxymethyl chitosan (CMC) nanoparticle loaded with a photosensitizer hypocrellin A (HA), named TF-HA-CMC-PLGA NPs. Morphology, size distribution, Fourier transform infrared (FT-IR) spectra, encapsulation efficiency, and loading capacity of TF-HA-CMC-PLGA NPs were characterized. In vitro TF-HA-CMC-PLGA NPs presented weak dark cytotoxicity and significant photo-cytotoxicity with strong reactive oxygen species (ROS) generation and apoptotic cancer cell death. In vivo photodynamic antitumor efficacy of TF-HA-CMC-PLGA NPs was investigated with an A549 (TFR positive) tumor-bearing model in male athymic nude mice. TF-HA-CMC-PLGA NPs caused tumor delay with a remarkable tumor inhibition rate of 63% for 15 days. Extensive cell apoptosis in tumor tissue and slight side effects in normal organs were observed. The results indicated that TDDS has great potential to enhance PDT therapeutic efficacy.
Highlights
Shiraia bambusicola has been used as a folk medicine to treat Rheumatoid arthritis, pertussis, and numbness of limbs for several centuries in China (Kishi et al, 1991)
Narrow particles size distribution of Hypocrellin A (HA)-carboxymethyl chitosan (CMC)-PLGA transferrin-modified Poly(D (NPs) (92– 116 nm) and TF-HA-CMC-PLGA NPs (96–156 nm) in aqueous solution were analyzed by dynamic light scattering (DLS)
Red fluorescence of HA in both HACMC-PLGA NPs and TF-HA-CMC-PLGA NPs exhibited the homogeneous dispersibility of nanoparticles in aqueous solution (Figures 3C,D)
Summary
Shiraia bambusicola has been used as a folk medicine to treat Rheumatoid arthritis, pertussis, and numbness of limbs for several centuries in China (Kishi et al, 1991). Hypocrellin A (HA) isolated from S. bambusicola is a main active constituent of perylenequinone pigments (Zhao et al, 2016). Many researches have revealed that HA possesses excellent light-induced antimicrobial, antiviral, and anticancer activity (Hirayama et al, 1997; Su et al, 2011; Xie et al, 2014). These activities of HA are typical applications of photodynamic therapy (PDT).
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