title: Tumor-Homing and Penetrating Peptide-Functionalized Photosensitizer-Conjugated PEG-PLA Nanoparticles for Chemo-Photodynamic Combination Therapy of Drug-Resistant Cancer.
abstract: The combination of photodynamic therapy (PDT) and chemotherapy holds great potential in combating drug-resistant cancers. However, the major challenge that lies ahead is how to achieve high coloading capacity for both photosensitizer and chemo-drugs and how to gain efficient delivery of drugs to the drug-resistant tumors. In this study, we prepared a nanovehicle for codelivery of photosensitizer (pyropheophorbide-a, PPa) and chemo-drugs (paclitaxel, PTX) based on the synthesis of PPa-conjugated amphiphilic copolymer PPa-PLA-PEG-PLA-PPa. The obtained nanoparticles (PP NP) exhibited a satisfactory high drug-loading capacity for both drugs. To achieve effective tumor-targeting therapy, the surface of PP NP was decorated with a tumor-homing and penetrating peptide F3. In vitro cellular experiments showed that F3-functionalized PP NP (F3-PP NP) exhibited higher cellular association than PP NP and resulted in the strongest antiproliferation effect. In addition, compared with the unmodified nanoparticles, F3-PP NP exhibited a more preferential enrichment at the tumor site. Pharmacodynamics evaluation in vivo demonstrated that a longer survival time was achieved by the tumor-bearing mice treated with PP NP (+laser) than those treated with chemotherapy only or PDT only. Such antitumor efficacy of combination therapy was further improved following the F3 peptide functionalization. Collectively, these results suggested that targeted combination therapy may pave a promising way for the therapy of drug-resistant tumor.
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University , 826 Zhangheng Road, Shanghai 201203, P. R. China.
authors.forename: Xingye
authors.initials: X
authors.lastname: Feng
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University , 826 Zhangheng Road, Shanghai 201203, P. R. China.
authors.forename: Di
authors.initials: D
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University , 826 Zhangheng Road, Shanghai 201203, P. R. China.
authors.forename: Ting
authors.initials: T
authors.lastname: Kang
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University , 826 Zhangheng Road, Shanghai 201203, P. R. China.
authors.forename: Jianhui
authors.initials: J
authors.lastname: Yao
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University , 826 Zhangheng Road, Shanghai 201203, P. R. China.
authors.forename: Yixian
authors.initials: Y
authors.lastname: Jing
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University , 826 Zhangheng Road, Shanghai 201203, P. R. China.
authors.forename: Tianze
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University , 826 Zhangheng Road, Shanghai 201203, P. R. China.
authors.forename: Jingxian
authors.initials: J
authors.lastname: Feng
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University , 826 Zhangheng Road, Shanghai 201203, P. R. China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiaotong University School of Medicine , 280 South Chongqing Road, Shanghai 200025, P. R. China.
authors.forename: Qingxiang
authors.initials: Q
authors.lastname: Song
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University , 826 Zhangheng Road, Shanghai 201203, P. R. China.
authors.forename: Nan
authors.initials: N
authors.lastname: Dong
authors.affiliation: Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiaotong University School of Medicine , 280 South Chongqing Road, Shanghai 200025, P. R. China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Gao
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University , 826 Zhangheng Road, Shanghai 201203, P. R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
keywords: combination therapy; multidrug resistance; nanoparticle; photodynamic therapy; tumor-homing peptide