Comparison of cationic liposome and PAMAM dendrimer for delivery of anti-Plk1 siRNA in breast cancer treatment

Abstract

Delivery of negatively charged, high molecular weight and unstable siRNA is difficult. The present study describes the development and comparison of cationic liposomes (CLs) and polyamidoamine (PAMAM) dendrimer generation 4 (PG4) nanocarriers of gene for cancer therapy. CLs and PG4 were complexed with anticancer siRNA (siPlk1) to form siPlk1-CLs lipoplex and siPlk1-PG4 dendriplex. siPlk1-CLs/PG4 complexes were characterized for average particle size, zeta potential, fluorescence and integrity of siPlk1 by agarose gel electrophoresis, ethidium bromide intercalation assay, circular dichroism, protection against RNase and stability in serum. The complexation of CLs/siPlk1 and PG4/siPlk1 were at a 100/1 and 2/1 charge ratio respectively. The CLs and PG4 were effective in protecting siPlk1 from RNase activity, also they enhanced the siPlk1 serum stability. Additionally, siPlk1-CLs and siPlk1-PG4 were evaluated by cell culture studies. In vitro anticancer activity study using MCF-7 cells showed that siPlk1-CLs and siPlk1-PG4 causes nearly similar cell death. Both siPlk1-CLs and siPlk1-PG4 resulted in enhanced cellular uptake of siPlk1 in MDA-MB-231 cells compared to naked siPlk1 solution. Cell cycle analysis suggested that increased cell population arrest in subG1 phase by siPlk1-CLs and siPlk1-PG4 compared to naked siPlk1 solution. These observations suggested that CLs and PG4 can be a potential carrier for siPlk1 delivery in breast cancer treatment.

Graphical Abstract

Keywords:

• Breast cancer
• cationic liposomes
• PAMAM dendrimer
• polo-like kinase 1
• siRNA

Acknowledgements

The authors are thankful to Director, NIPER-Hyderabad for providing required facilities.

Disclosure statement

The authors have no conflict of interest.

Compliance with ethical standards

All the experiments published in this manuscript comply with the current laws of the country in which they were performed.

Additional information

Funding

This work is supported by Indo-Polish joint project under India-Polish Inter-Governmental, Science & Technology Cooperation Program (DST/INT/POL/P-12/2014) and Government of India.