GSH-Activated NIR Fluorescent Prodrug for Podophyllotoxin Delivery

被引：70
作者：
Liu, Yajing [1 ,2 ]
Zhu, Shaojia [1 ,2 ]
Gu, Kaizhi [1 ,2 ]
Guo, Zhiqian [1 ,2 ]
Huang, Xiaoyu [3 ]
Wang, Mingwei [4 ]
Amin, Hesham M. [5 ]
Zhu, Weihong [1 ,2 ]
Shi, Ping [1 ,2 ]
机构：
[1] East China Univ Sci & Technol, Key Lab Adv Mat, State Key Lab Bioreactor Engn, 130 Meilong Rd, Shanghai 200237, Peoples R China
[2] East China Univ Sci & Technol, Inst Fine Chem, 130 Meilong Rd, Shanghai 200237, Peoples R China
[3] Chinese Acad Sci, Shanghai Inst Organ Chem, Key Lab Synthet & Self Assembly Chem Organ Funct, 345 Lingling Rd, Shanghai 200032, Peoples R China
[4] Fudan Univ, Shanghai Canc Ctr, 270 Dongan Rd, Shanghai 200032, Peoples R China
[5] Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, 1515 Holcombe Blvd, Houston, TX 77030 USA
来源：
ACS APPLIED MATERIALS & INTERFACES | 2017年 / 9卷 / 35期
关键词：
PPT; prodrug; NIR fluorescent reporter; DCM-S-PPT; mPEG-DSPE; AGGREGATION-INDUCED EMISSION; TARGETED DRUG-DELIVERY; IN-VIVO; SELECTIVE DETECTION; CANCER-THERAPY; GLUTATHIONE-REDUCTASE; ANTICANCER AGENTS; PROBE; NANOPARTICLES; HOMOCYSTEINE;
D O I：
10.1021/acsami.7b07091
中图分类号：
TB3 [工程材料学];
学科分类号：
0805 ; 080502 ;
摘要：
Theranostic prodrug therapy enables the targeted delivery of anticancer drugs with minimized adverse effects and real-time in situ monitoring of activation of the prodrugs. In this work, we report the synthesis and biological assessment of the near-infrared (NIR) prodrug DCM-S-PPT and its amphiphilic copolymer (mPEG-DSPE)-encapsulated nanoparticles. DCM-S-PPT is composed of podophyllotoxin (PPT) as the anticancer moiety and a dicyanomethylene-4H-pyran (DCM) derivative as the NIR fluorescent reporter, which are linked by a thiol-specific cleavable disulfide bond. In vitro experiments indicated that DCM-S-PPT has low cytotoxicity and that glutathione (GSH) can activate DCM-S-PPT resulting in PPT release and a concomitant significant enhancement in NIR fluorescence at 665 nm. After being intravenously injected into tumor-bearing nude mice, DCM-S-PPT exhibited excellent tumor-activated performance. Furthermore, we have demonstrated that mPEG-DSPE as a nanocarrier loaded with DCM-S-PPT (mPEG-DSPE/DCM-S-PPT) showed even greater tumor-targeting performance than DCM-S-PPT on account of the enhanced permeability and retention effect. Its tumor-targeting ability and specific drug release in tumors make DCM-S-PPT a promising prodrug that could provide a significant strategy for theranostic drug delivery systems.
引用
收藏
页码：29496 / 29504
页数：9
相关论文
共 55 条
[1]   Development of Novel Tumor-Targeted Theranostic Nanoparticles Activated by Membrane-Type Matrix Metalloproteinases for Combined Cancer Magnetic Resonance Imaging and Therapy [J].
Ansari, Celina ;
Tikhomirov, Grigory A. ;
Hong, Su Hyun ;
Falconer, Robert A. ;
Loadman, Paul M. ;
Gill, Jason H. ;
Castaneda, Rosalinda ;
Hazard, Florette K. ;
Tong, Ling ;
Lenkov, Olga D. ;
Felsher, Dean W. ;
Rao, Jianghong ;
Daldrup-Link, Heike E. .
SMALL, 2014, 10 (03) :566-575
[2]  
Ayres D.C., 1990, Lignans: chemical, biological and clinical properties, P85
[3]   Targeted drug delivery to tumors: Myths, reality and possibility [J].
Bae, You Han ;
Park, Kinam .
JOURNAL OF CONTROLLED RELEASE, 2011, 153 (03) :198-205
[4]   Recent advances in the development of 1,8-naphthalimide based DNA targeting binders, anticancer and fluorescent cellular imaging agents [J].
Banerjee, Swagata ;
Veale, Emma B. ;
Phelan, Caroline M. ;
Murphy, Samantha A. ;
Tocci, Gillian M. ;
Gillespie, Lisa J. ;
Frimannsson, Daniel O. ;
Kelly, John M. ;
Gunnlaugsson, Thorfinnur .
CHEMICAL SOCIETY REVIEWS, 2013, 42 (04) :1601-1618
[5]   ANTINEOPLASTIC AND ANTIHERPETIC ACTIVITY OF SPERMIDINE CATECHOLAMIDE IRON CHELATORS [J].
BERGERON, RJ ;
CAVANAUGH, PF ;
KLINE, SJ ;
HUGHES, RG ;
ELLIOTT, GT ;
PORTER, CW .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1984, 121 (03) :848-854
[6]   Prodrug-based intracellular delivery of anticancer agents [J].
Bildstein, L. ;
Dubernet, C. ;
Couvreur, P. .
ADVANCED DRUG DELIVERY REVIEWS, 2011, 63 (1-2) :3-23
[7]   Podophyllotoxin [J].
Canel, C ;
Moraes, RM ;
Dayan, FE ;
Ferreira, D .
PHYTOCHEMISTRY, 2000, 54 (02) :115-120
[8]   Synthesis and cytotoxicity of podophyllotoxin analogues modified in the A ring [J].
Castro, A ;
del Corral, JMM ;
Gordaliza, M ;
Grande, C ;
Gómez-Zurita, A ;
García-Grávalos, D ;
San Feliciano, A .
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2003, 38 (01) :65-74
[9]   Synthesis, Biological Evaluation, and in Vivo Imaging of the first Camptothecin-Fluorescein Conjugate [J].
Chevalier, Arnaud ;
Dubois, Martine ;
Le Joncour, Vadim ;
Dautrey, Sebastien ;
Lecointre, Celine ;
Romieu, Anthony ;
Renard, Pierre-Yves ;
Castel, Helene ;
Sabot, Cyrille .
BIOCONJUGATE CHEMISTRY, 2013, 24 (07) :1119-1133
[10]   A two-photon fluorescent probe for ratiometric imaging of hydrogen peroxide in live tissue [J].
Chung, Chul ;
Srikun, Duangkhae ;
Lim, Chang Su ;
Chang, Christopher J. ;
Cho, Bong Rae .
CHEMICAL COMMUNICATIONS, 2011, 47 (34) :9618-9620
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