A smart O2-generating nanocarrier optimizes drug transportation comprehensively for chemotherapy improving
10.1016/j.apsb.2021.04.021
- Author:
Xiaojuan ZHANG
1
;
Chuanchuan HE
1
;
Yun SUN
2
;
Xiaoguang LIU
1
;
Yan CHEN
1
;
Chen CHEN
1
;
Ruicong YAN
1
;
Ting FAN
1
;
Tan YANG
1
;
Yao LU
1
;
Jun LUO
1
;
Xiang MA
1
;
Guangya XIANG
1
Author Information
1. School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
2. Institute of Traditional Chinese Medicine, Xinjiang Medical University, Urumqi 830011, China.
- Publication Type:Journal Article
- Keywords:
CTGF, connective tissue growth factor;
CaO2;
Chemotherapy;
DOX, doxorubicin;
DSPE-PEG2000, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000];
ECM, extracellular matrix;
EPR, enhanced permeability and retention;
FBS, fetal bovine serum;
HA, hyaluronic acid;
HAase, hyaluronidase;
HIF-1;
HIF-1α, hypoxia-inducible factor 1α;
Hypoxia;
MCTS, multicellular tumor spheroids;
MS, monostearin;
MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide;
MnO2;
NP, nanoparticle;
Nanoparticle;
OA, oleic acid;
P-gp, P-glycoprotein;
PDT, photodynamic therapy;
TEM, transmission electron microscopy;
TME, tumor microenvironment;
Transportation;
Tumor
- From:
Acta Pharmaceutica Sinica B
2021;11(11):3608-3621
- CountryChina
- Language:English
-
Abstract:
Drug transportation is impeded by various barriers in the hypoxic solid tumor, resulting in compromised anticancer efficacy. Herein, a solid lipid monostearin (MS)-coated CaO2/MnO2 nanocarrier was designed to optimize doxorubicin (DOX) transportation comprehensively for chemotherapy enhancement. The MS shell of nanoparticles could be destroyed selectively by highly-expressed lipase within cancer cells, exposing water-sensitive cores to release DOX and produce O2. After the cancer cell death, the core-exposed nanoparticles could be further liberated and continue to react with water in the tumor extracellular matrix (ECM) and thoroughly release O2 and DOX, which exhibited cytotoxicity to neighboring cells. Small DOX molecules could readily diffuse through ECM, in which the collagen deposition was decreased by O2-mediated hypoxia-inducible factor-1 inhibition, leading to synergistically improved drug penetration. Concurrently, DOX-efflux-associated P-glycoprotein was also inhibited by O2, prolonging drug retention in cancer cells. Overall, the DOX transporting processes from nanoparticles to deep tumor cells including drug release, penetration, and retention were optimized comprehensively, which significantly boosted antitumor benefits.
