Tumor Targeting Chemo- and Photodynamic Therapy Packaged in Albumin for Enhanced Anti-Tumor Efficacy

Abstract

Ke Zheng, 1–3 Hongyan Liu, 1 Xinxin Liu, 1 Ying Wang, 1 Linlin Li, 2 Shijie Li, 2 Jinping Xue, 2 Mingdong Huang 2 1College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, Shandong 266042, People’s Republic of China; 2College of Chemistry, Fuzhou University, Fuzhou, Fujian 350118, People’s Republic of China; 3Key Laboratory of Pharmaceutical Research for Metabolic Disease, Qingdao University of Science and Technology, Qingdao, Shandong 266042, People’s Republic of ChinaCorrespondence: Ke ZhengCollege of Chemical Engineering, Qingdao University of Science and Technology, 53 Zhengzhou Road, Qingdao, Shandong 266042, People’s Republic of ChinaTel [phone]Email [email protected]: Combination therapy for tumors is an important and promising strategy to improve therapeutic efficiency. This study aims at combining tumor targeting, chemo-, and photodynamic therapies to improve the anti-tumor performance.Patients and Methods: Human serum albumin (HSA), as a nontoxic and biodegradable drug carrier, was used to load hydrophobic photosensitizers (mono-substituted β-4-pyridyloxy phthalocyanine zinc, mPPZ) by a dilution-incubation-purification (DIP) strategy to form molecular complex HSA:mPPZ. This complex was cross-linked as nanoparticles, and then chemotherapy drug doxorubicin (DOX) was adsorbed into the nanoparticles to achieve combined photodynamic therapy and chemotherapy. Next, the surface of the obtained composite was modified by a tumor surface receptor (urokinase receptor) targeting agent (ATF-HSA) using a noncovalent method to obtain the final product (ATF-HSA@HSA:mPPZ:DOX nanoparticles, AHmDN).Results: AHmDN exhibited strong stability, remarkable cytotoxicity and higher uptake to tumor cells. Cell imaging analysis indicated that DOX was separated from AHmDN and uniformly distributed in cell nucleus while mPPZ localized in cytoplasm. The PDT activity of all the samples had been confirmed by the detection of intracellular ROS. In animal experiments, AHmDN was demonstrated to have a prominent tumor-targeting effect using a 3D imaging system. In addition, the enhanced antitumor effect of AHmDN in tumor-bearing mice was also been observed. Importantly, the tumor-targeting effect of such nanoparticles lasted for about 14 days after one injection.Conclusion: These albumin nanoparticles with combined functions of tumor targeting, chemotherapy and photodynamic therapy can highly enhance the anti-tumor effect. This drug delivery system can be applied to package other hydrophobic photosensitizers and chemotherapy drugs for improving therapeutic efficacy to tumors.Keywords: drug delivery system, combination therapy, phthalocyanine, doxorubicin, urokinase receptor mediated targeting  

Keywords

• drug delivery system
• combination therapy
• phthalocyanine
• doxorubicin
• urokinase receptor mediated targeting.