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BioImpacts. 2021;11(3): 199-207.
doi: 10.34172/bi.2021.27
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Original Research

Establishing the promising role of novel combination of triple therapeutics delivery using polymeric nanoparticles for Triple negative breast cancer therapy

Ranjita Misra 1* ORCID logo, Bamadeb Patra 2, Sudha Varadharaj 2, Rama Shanker Verma 2* ORCID logo

1 Sathyabama Institute of Science and Technology, Centre for nanoscience and nanotechnology, Chennai, India.
2 Bhupat and Jyoti Mehta School of Biosciences, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, India
Corresponding author: Rama S Verma, Email: vermars@iitm.ac.in vermars@iitm.ac.in

Abstract

Introduction: Triple-negative breast cancer (TNBC) is a lethal tumor with an advanced degree of metastasis and poor survivability as compared to other subtypes of breast cancer. TNBC which consists of 15 % of all types of breast cancer is categorized by the absence of expression of estrogen receptors (ER), progesterone receptors (PR) and human epidermal growth factor receptor-2 (HER2). This is the main reason for the failure of current hormonal receptor-based therapies against TNBCs, thus leading to poor patient outcomes. Therefore, there is a necessity to develop novel therapies targeting this devastating disease.
Methods: In this study, we have targeted TNBC by simultaneous activation of apoptosis through DNA damage via cytotoxic agent such as paclitaxel (PAC), inhibition of PARP activity via PARP inhibitor, olaparib (OLA) and inhibiting the activity of FOXM1 proto-oncogenic transcription factor by using RNA interference technology (FOXM1-siRNA) in nanoformulations. Experiments conducted in this investigation include cellular uptake, cytotoxicity and apoptosis study using MDA-MB-231 cells.
Results: The present study validates that co-delivery of two drugs (PAC and OLA) along with FOXM1-siRNA by cationic NPs, enhances the therapeutic outcome leading to greater cytotoxicity in TNBC cells.
Conclusion: The current investigation focuses on designing a multifunctional drug delivery platform for concurrent delivery of either PAC or PARP inhibitor (olaparib) and FOXM1 siRNA in chitosan-coated poly(D, L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) with the ability to emerge as a front runner therapeutic for TNBC therapy.
Keywords: TNBC, Nanoparticles, Paclitaxel, Olaparib, FOXM1-siRNA
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Submitted: 09 Mar 2020
Revision: 23 Jun 2020
Accepted: 04 Jul 2020
ePublished: 31 Jul 2020
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