TY - JOUR
T1 - Bilayer Nanocarriers with Protein-Acid Conjugation for Prolonged Release and Enhanced Anticancer Effects
AU - Hou, Heting
AU - Zhang, Dong
AU - Zeng, Jie
AU - Zhou, Liping
AU - Wang, Zhe
AU - Yao, Maojin
AU - Ren, Jiaoyan
AU - Hu, Nan
AU - Wang, Yi
N1 - Funding Information:
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 the 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:
© 2019 American Chemical Society.
PY - 2019/3/12
Y1 - 2019/3/12
N2 - Conventional chemotherapy, because of the high dose to keep the drug above the minimum effective concentration, possesses severe side effects and brings extra pain to patients. A controlled release drug delivery system, which is a bilayer self-assembled nanoparticle (NP) in this study, can solve this problem. Zein, a biodegradable natural protein from corn, was selected for the first layer of the drug encapsulation. The second layer was formed via the reversible ionic hydrogen bonds between zein and folic acid (FA), which was selected because of the two carboxylic acids and one amine group in its simple structure. Doxorubicin (DOX), a popular anticancer drug, was selected as the drug model to form the bilayer drug nanoencapsulation FA-NP-DOX. The in vitro controlled release profile of FA-NP-DOX was obtained. The in vivo pharmacokinetics and anticancer activity of FA-NP-DOX in tumor-xenografted animal models were also conducted. Compared to the zein nanoencapsulation of DOX (NP-DOX) and pure DOX, FA-NP-DOX showed comparable in vitro cytotoxicity but much longer in vitro controlled release time and in vivo circulation time. Both FA-NP-DOX and NP-DOX showed enhanced therapeutical efficiency in vivo than pure DOX. It is concluded that the bilayer self-assembled NP of zein and FA highly prolonged the controlled release and enhanced the therapeutic efficiency of the anticancer drug.
AB - Conventional chemotherapy, because of the high dose to keep the drug above the minimum effective concentration, possesses severe side effects and brings extra pain to patients. A controlled release drug delivery system, which is a bilayer self-assembled nanoparticle (NP) in this study, can solve this problem. Zein, a biodegradable natural protein from corn, was selected for the first layer of the drug encapsulation. The second layer was formed via the reversible ionic hydrogen bonds between zein and folic acid (FA), which was selected because of the two carboxylic acids and one amine group in its simple structure. Doxorubicin (DOX), a popular anticancer drug, was selected as the drug model to form the bilayer drug nanoencapsulation FA-NP-DOX. The in vitro controlled release profile of FA-NP-DOX was obtained. The in vivo pharmacokinetics and anticancer activity of FA-NP-DOX in tumor-xenografted animal models were also conducted. Compared to the zein nanoencapsulation of DOX (NP-DOX) and pure DOX, FA-NP-DOX showed comparable in vitro cytotoxicity but much longer in vitro controlled release time and in vivo circulation time. Both FA-NP-DOX and NP-DOX showed enhanced therapeutical efficiency in vivo than pure DOX. It is concluded that the bilayer self-assembled NP of zein and FA highly prolonged the controlled release and enhanced the therapeutic efficiency of the anticancer drug.
UR - http://www.scopus.com/inward/record.url?scp=85062320877&partnerID=8YFLogxK
U2 - 10.1021/acs.langmuir.8b02882
DO - 10.1021/acs.langmuir.8b02882
M3 - Journal article
C2 - 30727729
AN - SCOPUS:85062320877
SN - 0743-7463
VL - 35
SP - 3710
EP - 3716
JO - Langmuir
JF - Langmuir
IS - 10
ER -