title: Tumor homing cell penetrating peptide decorated nanoparticles used for enhancing tumor targeting delivery and therapy.
abstract: Specific targeting ability and good tissue penetration are two critical requirements for tumor targeted delivery systems. Systematical selected peptides from a library may meet these two requirements. RLW was such a cell penetrating peptide that could specifically target to non-small cell lung cancer cells (A549). In this study, RLW was linked onto nanoparticles (RNPs) and then the RNPs were used for lung cancer targeting delivery. A traditional cell penetrating peptide, R8 (RRRRRRRR), was used as control. In vitro cellular uptake study demonstrated that modification with RLW specifically enhanced the uptake by A549 cells rather than human umbilical vein endothelial cells, while modification with R8 increased the uptake by both cells. Furthermore, the modification with RLW specifically elevated the penetration into A549 tumor spheroids rather than glioma cell (U87, used as in vivo control) spheroids. And the in vivo imaging further demonstrated RNPs could target to A549 xenografts rather than U87 xenografts. Importantly, the distribution of RNPs in normal organs was approximately the same as that of unmodified nanoparticles. However, R8 modified nanoparticles elevated the distribution in almost all the tissues. These results demonstrated that RLW was superior in A549 tumor targeted delivery. After loaded with docetaxel, an anti-microtube agent, different formulations could effectively induce the A549 cell apoptosis, and inhibit the growth of A549 spheroids in vitro. While in vivo, RNPs displayed the best antitumor effect. The tumor volume was significantly lower than other groups, which was only 33.3% as that of saline group. In conclusion, in vitro RLW could specifically target to A549 cells and enhance the cytotoxicity of docetaxel. In vivo, RLW could significantly enhance the A549 xenografts targeting delivery and led to improved antitumor effect.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu 610041, China. Electronic address: gaohuile@scu.edu.cn.
authors.forename: Huile
authors.initials: H
authors.lastname: Gao
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu 610041, China.
authors.forename: Qianyu
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu 610041, China.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Xinguo
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu 610041, China. Electronic address: qinhe@scu.edu.cn.
authors.forename: Qin
authors.initials: Q
authors.lastname: He
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D057846:Cell-Penetrating Peptides / Q000008:administration & dosage* / Q000627:therapeutic use; D000077143:Docetaxel; D016503:Drug Delivery Systems; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage* / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D011091:Polyesters; D011092:Polyethylene Glycols / Q000737:chemistry; D043823:Taxoids / Q000008:administration & dosage* / Q000627:therapeutic use; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D057846:Cell-Penetrating Peptides; D011091:Polyesters; D043823:Taxoids; D000077143:Docetaxel; C016240:polycaprolactone; D011092:Polyethylene Glycols
keywords: Cell penetrating peptide; Non-small cell lung carcinoma; Targeted drug delivery; Tumor homing