Citation: Yi-bo Qin, Peng-xiang Yang, Sheng-bin Shi, Hong-fan Sun, Chuang-nian Zhang, De-ling Kong. Redox-sensitive Alginate Prodrug Nanoparticles for Tumor Photodynamic Therapy[J]. Acta Polymerica Sinica, ;2018, 0(7): 909-916. doi: 10.11777/j.issn1000-3304.2018.18039 shu

Redox-sensitive Alginate Prodrug Nanoparticles for Tumor Photodynamic Therapy

1.
Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300192
2.
Key Laboratory of Bioactive Materials, Ministry of Education, State Key Laboratory of Medicinal Chemical Biology, College of Life Science, Nankai University, Tianjin 300071

Corresponding author: Chuang-nian Zhang, cnzhang@mail.nankai.edu.cn De-ling Kong, kongdeling@nankai.edu.cn
Received Date: 2 February 2018
Revised Date: 3 March 2018
Available Online: 7 May 2018

Nanoparticles have been extensively explored as an effective means to deliver photosensitizers for photodynamic therapy (PDT) against cancer. In this work, Pheophorbide A (PheoA), a hydrophobic photosensitizer, was conjugated to natural polysaccharide alginate (PheoA-ALG) via a redox-sensitive disulfide linkage. The critical aggregation concentration (CAC) of PheoA-ALG in aqueous solution was 73.51 μg/mL, detected by pyrene monomer fluorescence probe technology. The resulting amphiphilic PheoA-ALG could form self-assembled nanoparticles (PheoA-ALG NPs) in an aqueous medium as prodrug nanoparticles for tumor photodynamic therapy. The physical and chemical properties of PheoA-ALG NPs were studied. TEM and DLS revealed that PheoA-ALG NPs were monodisperse spherical structures with a hydrodynamic diameter about 198 nm. PheoA release profiles in vitro indicated that PheoA release from PheoA-ALG NPs was redox-sensitive. Whereafter, the cellular uptake and cytotoxicity of PheoA-ALG NPs were investigated in vitro. Cellular uptake results showed that PheoA-ALG NPs were readily taken up by B16 tumor cells and enhanced PheoA uptake was detectable in PheoA-ALG NPs-treated B16 cells in comparison to carrier free drugs. Under light irradiation, PheoA-ALG NPs also elicited intracellular ROS generation, which led to an enhanced toxicity in B16 cells both in vitro and in vivo. The CCK-8 assay showed that PheoA-ALG NPs had good cellular compatibility without cytotoxic in vitro without light irradiation, and PheoA-ALG NPs exhibited light dependent cytotoxic response to B16 cells. After light irradiation, IC50 of PheoA-ALG NPs decreased to 0.16 μg mL⁻¹, which was about 0.67-fold lower than those of the free PheoA groups with light irradiation. In vivo anti-tumor efficacy of PheoA-ALG NPs was assessed using B16 tumor-bearing mice. Notably, mice treated with PheoA-ALG NPs under light irradiation displayed the highest inhibition ratio of 72.8%, among those treated with free PheoA (45.8%). These results suggest that PheoA-ALG NPs have good potential for tumor photodynamic therapy.
- Alginate,
- Redox-sensitive,
- Prodrug nanoparticle,
- Photodynamic therapy
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