Luteinizing Hormone-Releasing Hormone (LHRH)-Conjugated Cancer Drug Delivery from Magnetite Nanoparticle-Modified Microporous Poly-Di-Methyl-Siloxane (PDMS) Systems for the Targeted Treatment of Triple Negative Breast Cancer Cells

Author:

Eluu Stanley C.12ORCID,Obayemi John D.34ORCID,Yiporo Danyuo56,Salifu Ali A.7,Oko Augustine O.28,Onwudiwe Killian9,Aina Toyin10,Oparah Josephine C.11,Ezeala Chukwudi C.1112,Etinosa Precious O.3ORCID,Osafo Sarah A.1314,Ugwu Malachy C.1,Esimone Charles O.1,Soboyejo Winston O.3415

Affiliation:

1. Department of Pharmaceutical Microbiology and Biotechnology, Nnamdi Azikiwe University, Ifite Awka 420110, Nigeria

2. Department of Biotechnology, Ebonyi State University, Abakaliki 480101, Nigeria

3. Department of Mechanical and Material Science Engineering, Higgins Lab, Worcester Polytechnic Institute (WPI), 100 Institute Road, Worcester, MA 01609, USA

4. Department of Biomedical Engineering, Worcester Polytechnic Institute, Gateway Park Life Sciences and Bioengineering Centre, 60 Prescott Street, Worcester, MA 01609, USA

5. Department of Mechanical Engineering, Ashesi University, Berekuso PMB CT3, Ghana

6. Department of Mechanical Engineering, Academic City University College, Haatso-Accra P.O. Box AD 421, Ghana

7. Department of Engineering, Morrissey College of Arts and Science, Boston College, Chestnut Hill, MA 02467, USA

8. Department of Biology and Biotechnology, David Umahi Federal University of Health Sciences, Uburu 480101, Nigeria

9. Aerospace and Mechanical Engineering, University of Notre Dame, Notre Dame, IN 46556, USA

10. Department of Biomedical Engineering, Collage of Engineering, Afe Babalola University, KM 8.5 Afe Babalola Way, Ado-Ekiti 360001, Nigeria

11. Department of Material Science, African University of Science and Technology, Km 10 Airport Road, Abuja 900107, Nigeria

12. Department of Biotechnology, Worcester State University, Worcester, MA 01602, USA

13. Department of Material Science and Engineering, University of Ghana, Legon, Accra P.O. Box LG 1181, Ghana

14. Biomaterial Science Department, Dental School, College of Health Sciences, University of Ghana, Korle bu, Accra P.O. Box KB 52, Ghana

15. Department of Engineering, SUNY Polytechnic Institute,100 Seymour Rd, Utica, NY 13502, USA

Abstract

This study presents LHRH conjugated drug delivery via a magnetite nanoparticle-modified microporous Poly-Di-Methyl-Siloxane (PDMS) system for the targeted suppression of triple-negative breast cancer cells. First, the MNP-modified PDMS devices are fabricated before loading with targeted and untargeted cancer drugs. The release kinetics from the devices are then studied before fitting the results to the Korsmeyer–Peppas model. Cell viability and cytotoxicity assessments are then presented using results from the Alamar blue assay. Apoptosis induction is then elucidated using flow cytometry. The in vitro drug release studies demonstrated a sustained and controlled release of unconjugated drugs (Prodigiosin and paclitaxel) and conjugated drugs [LHRH conjugated paclitaxel (PTX+LHRH) and LHRH-conjugated prodigiosin (PG+LHRH)] from the magnetite nanoparticle modified microporous PDMS devices for 30 days at 37 °C, 41 °C, and 44 °C. At 24, 48, 72, and 96 h, the groups loaded with conjugated drugs (PG+LHRH and PTX+LHRH) had a significantly higher (p < 0.05) percentage cell growth inhibition than the groups loaded with unconjugated drugs (PG and PTX). Additionally, throughout the study, the MNP+PDMS (without drug) group exhibited a steady rise in the percentage of cell growth inhibition. The flow cytometry results revealed a high incidence of early and late-stage apoptosis. The implications of the results are discussed for the development of biomedical devices for the localized and targeted release of cancer drugs that can prevent cancer recurrence following tumor resection.

Funder

Pan African Material Institute

Worcester Polytechnic Institute

SUNY Polytechnic Institute

Publisher

MDPI AG

Reference57 articles.

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