John Garner

PEG-PLGA from PolySciTech used in development of dual-drug loaded nanoparticles for cisplatin-resistant ovarian cancer treatment

Blog Post created by John Garner on Apr 9, 2018

2018 Wortmannin-cisplatin ovarian cancer treatment.jpg

Despite effective first-line therapies based on platinum-type drugs, ovarian cancer remains one of the deadliest gynecological diseases in the USA. The incidence of relapse is high, as is the development of platinum-resistant ovarian cancer lines that cannot be treated well using cisplatin. Recently, researchers at University of North Carolina at Chapel Hill, Westminster College, Peking Union Medical College and China Medical University (China) used mPEG-PLGA (Polyvivo AK029)  and PLGA ( PolyVivo AP087) from PolySciTech ( to develop nanoparticles that deliver both wortmannin and cisplatin. They found this co-delivery system was very effective against ovarian cancer models in which the cancer was resistant to platinum-based drugs, as the wortmannin prevented the cancer from repairing its own DNA. This research holds promise for development of therapies against drug-resistant cancers. Read more: Zhang, Maofan, C. Tilden Hagan, Yuangzeng Min, Hayley Foley, Xi Tian, Feifei Yang, Yu Mi et al. "Nanoparticle co-delivery of wortmannin and cisplatin synergistically enhances chemoradiotherapy and reverses platinum resistance in ovarian cancer models." Biomaterials (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. Keywords: Nanoparticle; Combination therapy; Platinum resistance; Treatment synergy; Ovarian cancer”


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