CD44-Receptor Targeted Gold-Doxorubicin Nanocomposite for Pulsatile Chemo-Photothermal Therapy of Triple-Negative Breast Cancer Cells

Dnyaneshwar Kalyane; Suryanarayana Polaka; Nupur Vasdev; Rakesh Kumar Tekade

doi:10.3390/pharmaceutics14122734

CD44-Receptor Targeted Gold-Doxorubicin Nanocomposite for Pulsatile Chemo-Photothermal Therapy of Triple-Negative Breast Cancer Cells

Pharmaceutics. 2022 Dec 6;14(12):2734. doi: 10.3390/pharmaceutics14122734.

Authors

Dnyaneshwar Kalyane¹, Suryanarayana Polaka¹, Nupur Vasdev¹, Rakesh Kumar Tekade¹

Affiliation

¹ National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad, An Institute of National Importance, Opposite Air Force Station, Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Government of India, Gandhinagar 382355, India.

Abstract

This study reports the CD44 receptor-targeted gold-doxorubicin nanocomposite (TGNC-DOX) for pulsatile chemo-photothermal therapy of triple-negative breast cancer (TNBC). The developed TGNC-DOX was nanometric, having a particle size of 71.34 ± 3.66 nm. The doxorubicin was loaded by electrostatic interaction with high entrapment and loading efficiency (>75%). TGNC-DOX showed potent photothermal response and reversible photothermal stability following irradiation with 808 nm NIR laser irradiation. Further, TGNC-DOX showed laser-responsive and pH-dependent drug release behavior suggesting its suitability for chemo-photothermal therapy, specifically at the tumor microenvironment site. Cellular viability, cellular uptake, ROS generation, and apoptosis assays suggested selective localization of TGNC-DOX in cancer cells that showed a significant cytotoxic effect against MDA-MB-231 breast cancer cells. Moreover, the developed TGNC-DOX showed ferroptosis in MDA-MB-231 cells. The event of TGNC-DOX-mediated thermal ablation is marked by a significant generation of reactive oxygen species (ROS) and apoptosis, as affirmed by flow cytometry. NIR-808 laser-responsive photothermal therapy of cancer cells was found to be more effective than without NIR-808 laser-treated cells, suggesting the fundamental role of photothermal ablation. The outcome concludes developed TGNC-DOX is a novel and potential tool to mediate laser-guided chemo-photothermal ablation treatment of cancer cells.

Keywords: CD44 receptor targeting; ROS generation; breast cancer; chemo-photothermal therapy; gold nanocomposite; thermal ablation.

Grants and funding

The authors would also like to acknowledge the Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, India, for supporting research on cancer-targeted nanomedicine at NIPER-Ahmedabad. RKT would like to acknowledge the Science and Engineering Research Board (Statutory Body Established through an Act of Parliament: SERB Act 2008), Department of Science and Technology, Government of India for a grant (Grant no. ECR/2016/001964) and Core Research Grant funding (File Number: CRG/2021/005402) in Dr. Tekade’s Laboratory. RKT would also like to acknowledge the Indian Council of Medical Research (ICMR), New Delhi, for grant File Id: 2021-14161 for research work on diabetic wound healing. RKT would also like to acknowledge Indian Council of Medical Research (ICMR), New Delhi for the senior research fellowship grant (File No-5/3/8/53/ITR-F/2020).