title: Anti-Fas Antibody Conjugated Nanoparticles Enhancing the Antitumor Effect of Camptothecin by Activating the Fas-FasL Apoptotic Pathway.
abstract: Emerging evidence suggest that the introduction of Fas ligand (FasL) can enhance the Fas-dependent apoptosis and induce durable immune responses against tumor. However, selective triggering of apoptosis in tumor cells while sparing normal cells remains a great challenge for the application of FasL-based therapeutic strategies. Herein, smart nanoparticles (NPs) with a sandwich structure were fabricated. These NPs consist of a matrix metalloproteinase (MMP) cleavable PEG outer layer, an anti-Fas antibody middle layer, and a camptothecin (CPT)-loaded inner core. They could accumulate at a tumor site by the enhanced permeability and retention (EPR) effect. The removable PEG layer protects the cytotoxic anti-Fas antibody from premature contact with normal tissues, thus avoiding the unexpected lethal side effect before they reach the tumor site. Due to the high level of MMP expressed by tumor cells inside the tumor tissue, these NPs would shed their PEG layers, resulting in the exposure of anti-Fas antibody to bind the Fas receptor and triggering the apoptosis of tumor cells. Results of Western blot confirmed that these NPs could mimic the function of activated cytotoxic lymphocyte (CTL) to activate the Fas-FasL apoptosis pathway of tumor cells. With the aid of CPT payload, these anti-Fas antibody conjugated NPs achieved a high tumor inhibition in the B16 allograft tumor animal model. The design of these NPs provides a method for delivering cytotoxic ligand to targeting tissue, which may be valuable in cancer therapy.
authors.affiliation: Institute of Materials Engineering and Collaborative Innovation Center of Chemistry for Life Sciences, College of Engineering and Applied Sciences, Nanjing University , Nanjing, 210093, China.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Yu
authors.forename: Jian
authors.initials: J
authors.lastname: He
authors.affiliation: Institute of Materials Engineering and Collaborative Innovation Center of Chemistry for Life Sciences, College of Engineering and Applied Sciences, Nanjing University , Nanjing, 210093, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Lu
authors.affiliation: Institute of Materials Engineering and Collaborative Innovation Center of Chemistry for Life Sciences, College of Engineering and Applied Sciences, Nanjing University , Nanjing, 210093, China.
authors.forename: Da
authors.initials: D
authors.lastname: Huo
authors.affiliation: Institute of Materials Engineering and Collaborative Innovation Center of Chemistry for Life Sciences, College of Engineering and Applied Sciences, Nanjing University , Nanjing, 210093, China.
authors.forename: Shanmei
authors.initials: S
authors.lastname: Yuan
authors.forename: Zhengyang
authors.initials: Z
authors.lastname: Zhou
authors.forename: Peipei
authors.initials: P
authors.lastname: Xu
authors.affiliation: Institute of Materials Engineering and Collaborative Innovation Center of Chemistry for Life Sciences, College of Engineering and Applied Sciences, Nanjing University , Nanjing, 210093, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Hu
mesh_terms: D000818:Animals; D017209:Apoptosis; D002166:Camptothecin; D045744:Cell Line, Tumor; D053758:Nanoparticles; D019014:fas Receptor
chemical_list: D019014:fas Receptor; D002166:Camptothecin
keywords: anti-Fas antibody; camptothecin; matrix metalloproteinase; nanoparticles; polycaprolactone