Establishing the Promising Role of Novel Combination of Triple Therapeutics Delivery Using Polymeric Nanoparticles for Triple Negative Breast Cancer Therapy

Overview

Journal Bioimpacts

Specialty Biomedical Engineering

Date 2021 Aug 2

PMID 34336608

Citations 5

Authors

Ranjita Misra

Bamadeb Patra

Sudha Varadharaj

Rama Shanker Verma

Affiliations

Soon will be listed here.

Abstract

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. 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. 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. 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.

Citing Articles

Drug-loaded polymer-coated silver nanoparticles for lung cancer theranostics.

Misra R, Hazra S, Saleem S, Nehru S Med Oncol. 2024; 41(6):132.

PMID: 38687401 DOI: 10.1007/s12032-024-02372-y.

Recent Advances of Multifunctional PLGA Nanocarriers in the Management of Triple-Negative Breast Cancer.

Dinakar Y, Rajana N, Kumari N, Jain V, Mehra N AAPS PharmSciTech. 2023; 24(8):258.

PMID: 38097825 DOI: 10.1208/s12249-023-02712-7.

Endorsement of TNBC Biomarkers in Precision Therapy by Nanotechnology.

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The Current State of the Art in PARP Inhibitor-Based Delivery Nanosystems.

Cai L, Xu X, Chen W Pharmaceutics. 2022; 14(8).

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Active Targeted Nanoparticles for Delivery of Poly(ADP-ribose) Polymerase (PARP) Inhibitors: A Preliminary Review.

Sargazi S, Mukhtar M, Rahdar A, Barani M, Pandey S, Diez-Pascual A Int J Mol Sci. 2021; 22(19).

PMID: 34638660 PMC: 8508934. DOI: 10.3390/ijms221910319.

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