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Environmentally responsive dual-targeting nanotheranostics for overcoming cancer multidrug resistance
- Source :
- Science Bulletin. 64:705-714
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- The development of multiple drug resistance (MDR) to chemotherapy and subsequent treatment failures are major obstacles in cancer therapy. An attractive option for combating MDR is inhibiting the expression of P-glycoprotein (P-gp) in tumor cells. Here, we report a novel chemosensitizing agent, XMD8-92, which can down-regulate P-gp. To enhance the specificity of MDR chemotherapy, a promising nanotheranostic micelle system based on poly(ethylene glycol)-blocked-poly(L-leucine) (PEG-b-Leu) was developed to simultaneously carry the anticancer drug doxorubicin, chemosensitizing agent XMD8-92, and superparamagnetic iron oxide nanoparticles (SPIOs). Featured with MDR environmentally responsive dual-targeting capability, controllable drug delivery, and efficient magnetic resonance (MR) imaging characteristics, the prepared nanotheranostics (DXS@NPs) showed outstanding in vitro cytotoxicity on MDR cells (SCG 7901/VCR) with only 53% of cells surviving compared to 90% of DOX-treated cells. Furthermore, efficient tumor inhibition and highly reduced systemic toxicity were exhibited by MDR tumor-bearing mice treated with DXS@NPs. Overall, the environmentally responsive dual-targeting nanotheranostics represent a promising approach for overcoming cancer MDR.
- Subjects :
- Chemotherapy
Multidisciplinary
biology
Dual targeting
Chemistry
medicine.medical_treatment
Cancer
010502 geochemistry & geophysics
medicine.disease
01 natural sciences
Multiple drug resistance
Drug delivery
medicine
biology.protein
Cancer research
Chemosensitizing agent
Doxorubicin
0105 earth and related environmental sciences
P-glycoprotein
medicine.drug
Subjects
Details
- ISSN :
- 20959273
- Volume :
- 64
- Database :
- OpenAIRE
- Journal :
- Science Bulletin
- Accession number :
- edsair.doi...........c727bb636069794900f63a2d269aac0e