International Journal of Nanomedicine (Nov 2018)
Novel pH-sensitive zinc phthalocyanine assembled with albumin for tumor targeting and treatment
Abstract
Ying Wang,1,2 Ke Zheng,1 Guangshan Xuan,1 Mingdong Huang,3 Jinping Xue3 1College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, Shandong, China; 2Key Lab of Inorganic Synthetic and Applied Chemistry, State Key Lab Base of Eco-Chemical Engineering, College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao, Shandong, China; 3College of Chemistry, Fuzhou University, Fuzhou, Fujian, China Purpose: Zinc phthalocyanine (ZnPc) has been applied widely in photodynamic therapy (PDT) with high ROS-production capacity and intense absorption in the near-infrared region. However, weak tumor targeting and the aggregation tendency of ZnPc seriously affect the therapeutic effect of PDT. Therefore, overcoming the aggregation of ZnPc and enhancing its antitumor effect were the purpose of this study.Methods: In this study, we first found that the aggregation behaviors of the photosensitizer ZnPc(TAP)4, ZnPc substituted by tertiary amine groups, were regulated finely by pH and that ZnPc(TAP)4 could be disaggregated gradually as the pH descended. ZnPc(TAP)4 and human serum albumin (HSA) molecules were assembled into nanoparticles (NPs) for tumor targeting. Meanwhile, the chemotherapy drug paclitaxel (Ptx) was loaded into HSA NPs together with ZnPc(TAP)4 for dual antitumor effects. HSA NPs loading both ZnPc(TAP)4 and Ptx (NP–ZnPc[TAP]4–Ptx) were characterized by particle size and in vitro release. Cytotoxicity, subcellular localization, tumor targeting, and anticancer effect in vivo were investigated respectively.Results: We found that NP–ZnPc(TAP)4–Ptx had good stability with qualifying particle size. Interestingly, ZnPc(TAP)4 was released from the NPs and the photodynamic activity enhanced in the acidic environment of tumor. In addition, NP–ZnPc(TAP)4–Ptx had prominent cytotoxicity and time-dependent subcellular localization characteristics. Through a three-dimensional animal imaging system, NP–ZnPc(TAP)4–Ptx showed much-enhanced tumor targeting in tumor-bearing mice. Above all, NP–ZnPc(TAP)4–Ptx was demonstrated to have the synergistic anticancer effect of PDT and chemotherapy.Conclusion: NP–ZnPc(TAP)4–Ptx had enhanced tumor targeting for the pH-sensitive property of ZnPc(TAP)4 and the transport function of HSA. NP–ZnPc(TAP)4–Ptx possessed a double-anticancer effect through the combination of ZnPc(TAP)4 and Ptx. This drug-delivery system may also be used to carry chemotherapy drugs other than Ptx for improving antitumor effects. Keywords: photodynamic therapy, drug-delivery system, controlled release, chemotherapy, antitumor activity, combination therapy
