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Nanoparticle co-delivery of wortmannin and cisplatin synergistically enhances chemoradiotherapy and reverses platinum resistance in ovarian cancer models
- Source :
- Biomaterials. 169:1-10
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- Most ovarian cancer patients respond well to initial platinum-based chemotherapy. However, within a year, many patients experience disease recurrence with a platinum resistant phenotype that responds poorly to second line chemotherapies. As a result, new strategies to address platinum resistant ovarian cancer (PROC) are needed. Herein, we report that NP co-delivery of cisplatin (CP) and wortmannin (Wtmn), a DNA repair inhibitor, synergistically enhances chemoradiotherapy (CRT) and reverses CP resistance in PROC. We encapsulated this regimen in FDA approved poly(lactic-co-glycolic acid)-poly(ethylene glycol) (PLGA-PEG) NPs to reduce systemic side effects, enhance cellular CP uptake, improve Wtmn stability, and increase therapeutic efficacy. Treatment of platinum-sensitive ovarian cancer (PSOC) and PROC murine models with these dual-drug loaded NPs (DNPs) significantly reduced tumor burden versus treatment with combinations of free drugs or single-drug loaded NPs (SNPs). These results support further investigation of this NP-based, synergistic drug regimen as a means to combat PROC in the clinic.
- Subjects :
- Combination therapy
Polyesters
medicine.medical_treatment
Biophysics
Antineoplastic Agents
Bioengineering
02 engineering and technology
Article
Polyethylene Glycols
Biomaterials
Wortmannin
Mice
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Cell Line, Tumor
Platinum resistance
Animals
Humans
Medicine
Ovarian Neoplasms
Cisplatin
Drug Carriers
Chemotherapy
business.industry
Drug Synergism
Chemoradiotherapy
021001 nanoscience & nanotechnology
medicine.disease
Xenograft Model Antitumor Assays
Regimen
chemistry
Mechanics of Materials
030220 oncology & carcinogenesis
Ceramics and Composites
Cancer research
Nanoparticles
Female
0210 nano-technology
business
Ovarian cancer
medicine.drug
Subjects
Details
- ISSN :
- 01429612
- Volume :
- 169
- Database :
- OpenAIRE
- Journal :
- Biomaterials
- Accession number :
- edsair.doi.dedup.....469b51390dfd81c18c7ea1cb8c5a9943
- Full Text :
- https://doi.org/10.1016/j.biomaterials.2018.03.055