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Nitric oxide-releasing micelles with intelligent targeting for enhanced anti-tumor effect of cisplatin in hypoxia.
- Source :
-
Journal of nanobiotechnology [J Nanobiotechnology] 2021 Aug 16; Vol. 19 (1), pp. 246. Date of Electronic Publication: 2021 Aug 16. - Publication Year :
- 2021
-
Abstract
- Background: Hypoxic tumor microenvironment (TME) promotes tumor metastasis and drug resistance, leading to low efficiency of cancer chemotherapy. The development of targeted agents or multi-target therapies regulating hypoxic microenvironment is an important approach to overcome drug resistance and metastasis.<br />Methods: In this study, chitosan oligosaccharide (COS)-coated and sialic acid (SA) receptor-targeted nano-micelles were prepared using film dispersion method to co-deliver cisplatin (CDDP) and nitric oxide (NO) (denoted as CTP/CDDP). In addition, we explored the mechanisms by which NO reversed CDDP resistance as well as enhanced anti-metastatic efficacy in hypoxic cancer cells.<br />Results: Because of the different affinities of COS and SA to phenylboronic acid (PBA) under different pH regimes, CTP/CDDP micelles with intelligent targeting property increased cellular uptake of CDDP and enhanced cytotoxicity to tumors, but reduced systemic toxicity to normal organs or tissues. In addition, CTP/CDDP showed stimulus-responsive release in TME. In terms of anti-tumor mechanism, CTP/CDDP reduced CDDP efflux and inhibited epithelial-mesenchymal transition (EMT) process of tumor by down-regulating hypoxia-inducible factor-1α (HIF-1α), glutathione (GSH), multidrug resistance-associated protein 2 (MRP2) and matrix metalloproteinase 9 (MMP9) expression, thus reversing drug resistance and metastasis of hypoxic tumor cells.<br />Conclusions: The designed micelles significantly enhanced anti-tumor effects both in vitro and in vivo. These results suggested that CTP/CDDP represented a promising strategy to treat resistance and metastatic tumors.<br /> (© 2021. The Author(s).)
- Subjects :
- Animals
Antineoplastic Agents chemistry
BALB 3T3 Cells
Cell Line, Tumor
Chitosan chemistry
Drug Delivery Systems
Drug Resistance, Neoplasm drug effects
Humans
Hypoxia-Inducible Factor 1, alpha Subunit
Matrix Metalloproteinase 9 metabolism
Mice
Multidrug Resistance-Associated Protein 2 metabolism
Nitric Oxide chemistry
Particle Size
Tumor Microenvironment drug effects
Antineoplastic Agents pharmacology
Cisplatin pharmacology
Hypoxia drug therapy
Micelles
Nitric Oxide pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1477-3155
- Volume :
- 19
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of nanobiotechnology
- Publication Type :
- Academic Journal
- Accession number :
- 34399762
- Full Text :
- https://doi.org/10.1186/s12951-021-00989-z