Cholesterol and Morpholine Grafted Cationic Amphiphilic Copolymers for miRNA-34a Delivery

Saurabh Sharma, Samrat Mazumdar, Kishan S. Italiya, Tushar Date, Ram I. Mahato, Anupama Mittal, Deepak Chitkara

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

miR-34a is a master tumor suppressor playing a key role in the several signaling mechanisms involved in cancer. However, its delivery to the cancer cells is the bottleneck in its clinical translation. Herein we report cationic amphiphilic copolymers grafted with cholesterol (chol), N,N-dimethyldipropylenetriamine (cation chain) and 4-(2-aminoethyl)morpholine (morph) for miR-34a delivery. The copolymer interacts with miR-34a at low N/P ratios (∼2/1) to form nanoplexes of size ∼ 108 nm and a zeta potential ∼+39 mV. In vitro studies in 4T1 and MCF-7 cells indicated efficient transfection efficiency. The intracellular colocalization suggested that the copolymer effectively transported the FAM labeled siRNA into the cytoplasm within 2 h and escaped from the endo-/lysosomal environment. The developed miR-34a nanoplexes inhibited the breast cancer cell growth as confirmed by MTT assay wherein 28% and 34% cancer cell viability was observed in 4T1 and MCF-7 cells, respectively. Further, miR-34a nanoplexes possess immense potential to induce apoptosis in both cell lines.

Original languageEnglish (US)
Pages (from-to)2391-2402
Number of pages12
JournalMolecular Pharmaceutics
Volume15
Issue number6
DOIs
StatePublished - Jun 4 2018

Keywords

  • amphiphilic cationic polymer
  • anticancer therapy
  • miR-34a
  • nanoplexes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

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