Nanosystem Integrated with Photosensitizer and Novel Targeting Chemotherapy Agent for Gastric Cancer Chemo-Photodynamic Combined Therapy

作者：Xin, Jing; Wang, Sijia; Wang, Jing; Wang, Jiazhuang; Fu, Lei; Zhang, Luwei; Shen, Lijian; Zhang, Zhenxi^*; Yao, Cuiping^*

来源：Journal of Biomedical Nanotechnology, 2018, 14(8D): 1430-1447.

DOI：10.1166/jbn.2018.2598

• Nanosized Micelle F127
• ApoG(2)/Chemotherapy
• ALPcS(4)/Photodynamic Therapy
• Synergistic Anti-Tumor Effect
• Chemo-Photodynamic Combined Therapy
• Targeting Small Molecular Inhibitor

The poor cell membrane penetration ability of photosensitizers resulted in the limited antitumor effect, thereby hampered their potential in clinical translation. The high toxic side effect and multidrug resistance of chemotherapeutic agents during in clinical chemical therapy should be resolved. Nanosystem integrated with photosensitizer and novel targeting chemotherapy agent may be an effective strategy for overcoming clinical or preclinical drawbacks of monotherapy and enhancing therapeutic effect. Therefore, a nanosized micelle F127 integrated with Apogossypolone (ApoG(2)) and Al(III) phthalocyanine chloride tetrasulfonic acid (AlPcS4) (referred as F127-ApoG(2)@AlPcS4) was synthesized to induce the cell death quickly for reducing the risk of resistance and enhancing gastric cancer therapeutic efficiency by combining AlPcS4/photodynamic therapy and ApoG(2)/chemotherapy. Hydrophobic of ApoG(2) and hydrophilic of AlPcS4 self-assembled into this micelle to formation of core-shell structure based on the amphiphilic character of F127 micelle. The reactive oxygen species-dependent mitochondria membrane permeability was improved effectively because of reactive oxygen species generation of ApoG(2), thereby resulting in a considerable amount of AlPcS4 and ApoG(2) entering the mitochondrial. The AlPcS4 binding site was altered from the cytoplasm to the cell nucleus at higher concentration because of the existence of ApoG(2). With irradiation, ApoG(2) and AlPcS4 showed effective synergistic anti-tumor effect through inducing apoptosis due to singlet oxygen production regulated mainly by AlPcS4, reactive oxygen species accumulation and calcium overload regulated mainly by ApoG(2). Intranuclear AlPcS4 caused cell death through necrosis. The apoptosis induced by AlPcS4 was earlier than ApoG(2). In summary, F127-ApoG(2)@AlPcS4 quickly induced a long-lasting apoptosis that led to cell death, which could be a promising nanosized reagent for gastric cancer therapy based on chemo-photodynamic combined therapy.

• 出版日期2018-8
• 单位西安交通大学