ROS responsive polymeric micelles for triggered simultaneous delivery of PLK1 inhibitor/miR-34a and effective synergistic therapy in pancreatic cancer.

08:00 EDT 1st April 2019 | BioPortfolio

Summary of "ROS responsive polymeric micelles for triggered simultaneous delivery of PLK1 inhibitor/miR-34a and effective synergistic therapy in pancreatic cancer."

Ineffective drug delivery and poor prognosis are two major challenges in the treatment of pancreatic ductal adenocarcinoma (PDAC). While there is significant downregulation of tumor suppressor microRNA-34a (miR-34a), which targets many oncogenes related to proliferation, apoptosis and invasion, high expression level of Polo-like kinase 1 (PLK1) is closely associated with short survival rates of pancreatic cancer patients. Therefore, the objective is to co-deliver miR-34a mimic and small molecule PLK1 inhibitor volasertib (BI6727) using poly (ethylene glycol)-poly[aspartamidoethyl (p-boronobenzyl) diethyl ammonium bromide] (PEG-B-PAEBEA) This polymer can self-assemble into micelles of ~100 nm with 10 % drug loading of volasertib and form complex with miR-34a at the N/P ratio of 18 and higher. Combination treatment of volasertib and miR-34a displays synergistic effect and superior anti-proliferative activity along with an enhanced G2/M phase arrest and suppression of colony formation, leading to cell death due to potential c-myc targeting therapeutics. Orthotopic pancreatic tumor bearing NSG mice are scanned for fluorescence by IVIS after systemic administration of micelles encapsulating volasertib and miR-34a at doses of 5 mg/kg and 1 mg/kg, respectively. Cy5.5 concentration in plasma and major organs is determined by measuring fluorescence intensity. There is a significant reduction in tumor volume and negligible systemic toxicity as evident by hematological parameters and histological evaluation. In conclusion, PEG-B-PAEBEA micelles carrying volasertib and miR-34a mimic have great potential to improve drug delivery for pancreatic cancer treatment.


Journal Details

This article was published in the following journal.

Name: ACS applied materials & interfaces
ISSN: 1944-8252


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