TY - JOUR
T1 - Zein-Paclitaxel Prodrug Nanoparticles for Redox-Triggered Drug Delivery and Enhanced Therapeutic Efficiency
AU - Hou, Heting
AU - Zhang, Dong
AU - Lin, Jiewen
AU - Zhang, Yingying
AU - Li, Chengyong
AU - Wang, Zhe
AU - Ren, Jiaoyan
AU - Yao, Maojin
AU - Wong, Ka Hing
AU - Wang, Yi
N1 - Funding Information:
*E-mail: (K.-h.W.) [email protected]. *E-mail: (Y.W.) [email protected]. ORCID Chengyong Li: 0000-0003-0018-165X Ka-hing Wong: 0000-0003-0286-4921 Yi Wang: 0000-0003-1567-3358 Author Contributions ○H.H. and D.Z. contributed equally to this work Funding We thank the State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation) and Shenzhen Key Laboratory of Food Biological Safety Control for their support. This work is financially supported by the Shenzhen Basic Research (Layout of Disciplines) Project Fund (JCYJ20170413154810633), the General Research Fund (GRF) of Hong Kong (PolyU 153343/16P), the Health and Medical Research Fund (HMRF) of the Food and Health Bureau of Hong Kong (03144126, 05161016), and Central Research Fund of the Hong Kong Polytechnic University (4-BCA8, G-UA4C, G-YBJ7, and G-YBU1). We appreciate the help from the Material Research Center of the Hong Kong Polytechnic University.
Publisher Copyright:
© 2018 American Chemical Society.
PY - 2018/11/7
Y1 - 2018/11/7
N2 - Prodrug, in which the inactive parent drug with good bioavailability is metabolized into an active drug in the body, is one of the main strategies to target the disease site to improve the drug efficiency and reduce the adverse effects of chemotherapy. Because of the good capability of chemical modification, zein, a plant derived protein, and drugs can be conjugated through environmentally sensitive links to form prodrugs capable of triggered drug release. In this study, a novel prodrug was synthesized using paclitaxel (PTX), zein, and a disulfide linker, and nanoparticles were formed by self-assembly of the prodrug. An effective in vitro triggered release, 80-90% in 5 min, of the prodrug based nanoparticles (zein-S-S-PTX-NP) was successfully approached. The cytotoxicity of zein-S-S-PTX-NP as well as the zein encapsulation of PTX (zein-PTX-NP) and pure PTX on HeLa cells and NIH/3T3 fibroblast cells was tested using MTS assay. It showed that, after the treatment of zein-S-S-PTX-NP at the equivalent PTX concentrations of 0.1, 0.5, 1, and 5 μg/mL, respectively, zein-S-S-PTX-NP had zero damage to normal cells but a similar cytotoxicity to cancer cells as pure PTX. In the animal study, the tumor was 50% of the original size after the treatment of zein-S-S-PTX-NP for 9 days with 3 doses. This study suggested that the novel prodrug based nanoparticle zein-S-S-PTX-NP could be a promising approach in chemotherapy with targeted delivery, improved efficacy, and reduced side effects.
AB - Prodrug, in which the inactive parent drug with good bioavailability is metabolized into an active drug in the body, is one of the main strategies to target the disease site to improve the drug efficiency and reduce the adverse effects of chemotherapy. Because of the good capability of chemical modification, zein, a plant derived protein, and drugs can be conjugated through environmentally sensitive links to form prodrugs capable of triggered drug release. In this study, a novel prodrug was synthesized using paclitaxel (PTX), zein, and a disulfide linker, and nanoparticles were formed by self-assembly of the prodrug. An effective in vitro triggered release, 80-90% in 5 min, of the prodrug based nanoparticles (zein-S-S-PTX-NP) was successfully approached. The cytotoxicity of zein-S-S-PTX-NP as well as the zein encapsulation of PTX (zein-PTX-NP) and pure PTX on HeLa cells and NIH/3T3 fibroblast cells was tested using MTS assay. It showed that, after the treatment of zein-S-S-PTX-NP at the equivalent PTX concentrations of 0.1, 0.5, 1, and 5 μg/mL, respectively, zein-S-S-PTX-NP had zero damage to normal cells but a similar cytotoxicity to cancer cells as pure PTX. In the animal study, the tumor was 50% of the original size after the treatment of zein-S-S-PTX-NP for 9 days with 3 doses. This study suggested that the novel prodrug based nanoparticle zein-S-S-PTX-NP could be a promising approach in chemotherapy with targeted delivery, improved efficacy, and reduced side effects.
KW - paclitaxel
KW - prodrug
KW - redox-responsive
KW - self-assembly
KW - triggered release
KW - zein
UR - http://www.scopus.com/inward/record.url?scp=85056247654&partnerID=8YFLogxK
U2 - 10.1021/acs.jafc.8b04627
DO - 10.1021/acs.jafc.8b04627
M3 - Journal article
C2 - 30339011
AN - SCOPUS:85056247654
SN - 0021-8561
VL - 66
SP - 11812
EP - 11822
JO - Journal of Agricultural and Food Chemistry
JF - Journal of Agricultural and Food Chemistry
IS - 44
ER -