tLyP-1 Peptide Functionalized Human H Chain Ferritin for Targeted Delivery of Paclitaxel

Abstract

Yuanmeng Ma,1 Ruike Li,1 Yixin Dong,1 Chaoqun You,1,2 Shenlin Huang,1 Xun Li,1 Fei Wang,1 Yu Zhang1 1College of Chemical Engineering, Jiangsu Key Laboratory for the Chemistry and Utilization of Agro-Forest Biomass, Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, Jiangsu Key Laboratory of Biomass-Based Green Fuels and Chemicals, Nanjing Forestry University, Nanjing, 210037, People’s Republic of China; 2School of Chemistry and Chemical Engineering, Southeast University, Nanjing, 210089, People’s Republic of ChinaCorrespondence: Yu Zhang Tel [phone]Fax [phone]Email [email protected]: The aims of this study were to test the feasibility, targeting specificity and anticancer therapeutic efficacy of CendR motif tLyP-1 functionalized at the N-terminal of ferritin for paclitaxel (PTX) delivery.Methods: A tumor homing and penetrating peptide tLyP-1 was fused to the N-terminal of human H chain ferritin (HFtn) to generate a dual-targeting nanoparticle delivery system. PTX molecules were encapsulated into the HFtn nanocage using the disassembly/assembly method by adjusting pHs. Cellular uptake was examined by confocal laser scanning microscopy (CLSM) and flow cytometry. The MTT assay was used to test the cytotoxicity of various PTX-loaded NPs against MDA-MB-231 and SMMC-7721 tumor cells. The wound healing and cell migration assays were conducted to assess the inhibitory effect on cell motility and metastasis. The inhibition effect on the SMMC-7721 tumor spheroids was studied and penetration ability was evaluated by CLSM. The antitumor efficacy of PTX-loaded NPs was assessed in MDA-MB-231 breast cancer xenografted in female BALB/c nude mice.Results: Compared with HFtn-PTX, in vitro studies demonstrated that the tLyP-1-HFtn-PTX displayed enhanced intracellular delivery and better cytotoxicity and anti-invasion ability against both SMMC-7721 and MDA-MB-231 cells. The better penetrability and growth inhibitory effect on SMMC-7721 tumor spheroids were also testified. In vivo distribution and imaging demonstrated that the tLyP-1-HFtn-PTX NPs were selectively accumulated and penetrated at the tumor regions. Verified by the breast cancer cells model in BABL/c nude mice, tLyP-1-HFtn-PTX displayed higher in vivo therapeutic efficacy with lower systemic toxicity.Conclusion: Ferritin decorated with tumor-homing penetration peptide tLyP-1 at the N terminal could deliver PTX specifically inside the cell via receptor-mediated endocytosis with better efficacy. The peptide tLyP-1 which is supposed to work only at the C terminus showed enhanced tumor tissue penetration and antitumor efficacy, demonstrating that it also worked at the N-terminal of HFtn.Keywords: ferritin, tLyP-1 peptide, paclitaxel, neuropilin-1, transferrin receptor 1

Keywords

• ferritin
• tlyp-1 peptide
• paclitaxel
• neuropilin-1
• transferrin recptor1