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Lookup NU author(s): Dr Pankaj Singla, Dr Tommy Broughton, Saweta Garg, Dr Shoba AmarnathORCiD, Professor Marloes PeetersORCiD
This is the authors' accepted manuscript of a conference proceedings (inc. abstract) that has been published in its final definitive form by Controlled Released Society (CRS), 2023.
For re-use rights please refer to the publisher's terms and conditions.
Introduction: Targeted drug delivery is crucial for breast cancer treatment as it reduces side effects, drug resistance, and improves patient outcomes. Nanoparticles functionalized with specific molecules like antibodies, aptamers, or peptides are commonly used for this purpose but have several side effects and immune intolerance. 1,2 In this regard, we present a cost-effective alternative involving doubly-molecularly imprinted polymeric nanoparticles (nanoMIPs) that can specifically bind to Estrogen receptors (ER) and deliver doxorubicin (DOX) drug to ERα positive breast cancer cells (70% breast cancer is ERα positive), Figure 1.Methods: nanoMIPs and DOX loaded nanoMIPs were synthesized via solid phase synthesis employing an epitope of ERα receptor and range of monomers (Figure 2).3 All nanoMIPs batches were characterized using Dynamic Light Scattering (DLS), Transmission Electron Microscopy (TEM) and Surface Plasmon Resonance (SPR) and UV-visible Spectroscopy. In vitro cytotoxicity assay, flow cytometry and confocal microscopy were performed using two breast cancer cell lines MCF-7 (ERα positive) and MDA-MB-231 (ERα negative).Results: The synthesized nanoMIPs exhibited spherical morphology and hydrodynamic diameter were ranging from 120 to 200 nm. DOX loading has been confirmed by UV-visible Spectroscopy and DOX loaded nanoMIPs showed the binding affinity (KD) of 19.2 nM and 10.06 nM for epitope and whole ERα protein, respectively in SPR. Flow cytometry results indicated that nanoMIPs specifically bound to MCF-7 cells as compared to MDA- MB-231 cells. In addition, in vitro MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay showed the time dependent cytotoxicity against MCF-7 cells, while negligible cytotoxicity for ERα negative cells was observed.Conclusions/Impact: These findings suggest that these nanoMIPs can serve as a highly specific and effective drug delivery carrier for ERα positive breast cancer. Moreover, these nanoMIPs can be tailored for other cancers and chemotherapeutic drugs, where targeted drug delivery is required.Learning Objective 1: How targeted drug delivery with doubly-molecularly imprinted polymeric nanoparticles (nanoMIPs) can improve breast cancer treatment outcomes by reducing side effects and drug resistance.Learning Objective 2: The in vitro cell binding and cytotoxic assays demonstrate the potential of doubly- molecularly imprinted polymeric nanoparticles for use in nanomedicine for breast cancer treatment, and suggest that this technology could be adapted for other anticancer drugs and different cancer typesLearning Objective 3: Additionally, this research highlights the advantages of using doubly-molecularly imprinted polymeric nanoparticles over traditional ligands for targeted drug delivery, including lower cost and fewer side effects.
Author(s): Singla P, Broughton T, Sullivan MV, Garg S, Canfarotta F, Turner NW, Velliou E, Amarnath S, Peeters M
Publication type: Conference Proceedings (inc. Abstract)
Publication status: Published
Conference Name: Controlled Released Society (CRS) 2023 Annual Meeting
Year of Conference: 2023
Online publication date: 24/07/2023
Acceptance date: 02/04/2018
Date deposited: 19/06/2023
Publisher: Controlled Released Society (CRS)
URL: https://www.eventscribe.net/2023/CRSAnnualMeeting/
