Engineering of siRNA loaded PLGA Nano-Particles for highly efficient silencing of GPR87 gene as a target for pancreatic cancer treatment

Ceylan S., Bahadori F., Akbas F.

PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY, vol.25, no.7, pp.855-864, 2020 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 25 Issue: 7
  • Publication Date: 2020
  • Doi Number: 10.1080/10837450.2020.1745232
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Business Source Elite, Business Source Premier, Chemical Abstracts Core, EMBASE, International Pharmaceutical Abstracts, MEDLINE
  • Page Numbers: pp.855-864
  • Keywords: PLGA, gene silencing, GPR87, pancreatic cancer, nano drug delivery, NANOPARTICLES, DELIVERY, DNA, SIZE, THERAPEUTICS, OPTIMIZATION, MECHANISMS, MICELLES, DESIGN, MODEL
  • Bezmialem Vakıf University Affiliated: Yes


G protein-coupled receptor (GPCR) 87, is overexpressed in various cancer cells especially pancreatic cancer and plays a critical role in tumor cell survival. Nano-particles (NP) have become the essential vehicles for nucleotide internalization to the cell, due to the negative charge of nucleotides and their poor stability in blood circulation. In this study, the HEK293T cell linewas transfected with GPR87-plasmid after which the double-stranded RNA molecules targeting the GPR87 gene were prepared and purified. 1.1B4 cancer cell lines were used as model pancreatic cancer cells. Produced siRNA molecules were encapsulated in Poly(Lactic-Co-Glycolic Acid) (PLGA) nano-micelles using three different methods, two of which were according to literature with (siR-PLGA-S) or without (siR-PLGA-V) sonication. However, a new method was suggested to overcome problems such as poly-dispersity and large sizes of siR-PLGA-S and siR-PLGA-V. The new method consists of encapsulating siRNA using mild agitation to the pre-made PLGA NPs. The latter method provided mono-dispersed particles (siR-P-PLGA) with 92 nm size and desired Encapsulation Efficiency (EE%). siR-P-PLGA was able to silence the GPR-87 gene in a ratio of 83.9%, almost 41 times more effective than siR-PLGA-S and siR-PLGA-V in HEK 293 T cells. siR-P-PLGA was able to show a mild cytotoxic effect on 1.1B4 pancreatic cancer cells within 48 h.