Nano Drug Delivery System Constructed By Amphiphilic Zinc Phthalocyanine For Combined Anti-tumor Therapy

In the present world,the malignant tumor seriously threats human life and health.The development of new therapeutic strategies and effective anticancer drugs has become important measures for the treatment of tumors.Photodynamic therapy（PDT）is a modality of cancer treatment with non-invasion,less side effect and spatiotemporal selectivity,which has attracted more and more attention for the excellent antitumor effect.Many studies have reported that the combination of photodynamic therapy with other antitumor strategies exhibited synergistic antitumor therapeutic efficiency.However,how to achieve effective targeted delivery of multiple drugs is still a key problem to be solved.In this study,amphiphilic zinc phthalocyanine photosensitizer synthesized was combined with a variety of materials or drugs to construct nano drug delivery systems with properties of tumor-targeting and stimuli-sensitive drug controlled release.These drug delivery systems had tumor imaging functions and brought out significantly improved synergistic antitumor efficacy,which were effective implementation strategies of PDT combined with multiple antitumor therapies.Firstly,amphiphilic zinc phthalocyanine Zn Pc-（PEG）₅,modified cyclodextrin and the chemotherapeutic drug doxorubicin was assembled into nanoparticles Zn Pc-（PEG）₅:AC-CD:DOX.Zn Pc-（PEG）₅:AC-CD:DOX had p H-responsive controlled release property and can release doxorubicin at low p H environment of tumor to exert synergistic antitumor activity of PDT and chemotherapy.It was worth mentioning that the involvement of Zn Pc-（PEG）₅improved the dispersion of nanoparticles prepared.In addition,the excellent tumor targeting and strong fluorescence of Zn Pc-（PEG）₅endowed Zn Pc-（PEG）₅:AC-CD:DOX with significant tumor fluorescence indicator effect.This study not only expands the application of cyclodextrin,but also provides an efficient and feasible platform for combined photodynamic therapy.Secondly,in this study,amphiphilic zinc phthalocyanine Zn Pc（PEG）₄and phospholipid material DPPC was constructed into liposomes and encapsulated chemotherapy drug methotrexate.The prepared liposome Zn Pc（PEG）₄:MTX@Li POs can significantly improve the uptake of methotrexate by tumor cells.The significant tumor targeting and photo-triggered release property prompt methotrexate to be release at the tumor sites.Importantly,Zn Pc（PEG）₄:MTX@Li POs significantly reduced the side effects of methotrexate while exerting multiple synergistic antitumor activity.The constructed photodynamic photo-triggered liposomes provide effective and practical drug delivery strategies for combined PDT.