Work

Nanodiamond-Protein hybrid Nanoparticles: LHRH receptor targeted and co-delivery of doxorubicin and dasatinib for triple negative breast cancer therapy

Year: 2025

Type: article

Abstract: Triple Negative Breast Cancer (TNBC) is an aggressive type of breast cancer that is difficult to treat with conventional therapies. This study aimed to develop a novel therapeutic approach using a multifunctional protein-nanodiamond nanocomposite to co-deliver doxorubicin (DOX) and dasatinib (DAS) to cancer cells via luteinising hormone-releasing hormone receptors. Nanodiamonds help retain DOX in targeted cells, while α-lactalbumin efficiently encapsulates DAS, reducing side effects. We successfully formulated the nanocomposite with over 80 % drug loading efficiency for both drugs. The imine Schiff-base bond in the nanocomposite hydrolyzes in the acidic pH tumor environment, triggering approximately 65 % drug release after 72 h, compared to less than 20 % in neutral pH. In vitro studies showed enhanced uptake of DOX and DAS in TNBC cell lines, potentially overcoming drug resistance. The combined delivery showed enhanced synergistic cytotoxic effects in drug-resistant TNBC cell models. For example, in the MDA-MB-231 cell line, the IC50 of DOX dropped to 45.63 ng/ml, while in MDA-MB-468, DAS decreased to 35.85 ng/ml with nanoparticle therapy. In vivo experiments utilizing a TNBC mouse model demonstrated the therapeutic effectiveness of the nanocomposite, leading to a 55 % reduction in tumor growth and enhanced survival rates. All mice given the nanocomposite survived after 44 days, but most treated with the DOX/DAS mixture died by day 28. This research showcases multifunctional nanocomposites as targeted drug delivery systems for TNBC, improving drug uptake and cytotoxicity. This strategy presents a promising method for treating drug-resistant breast cancer, with potential clinical applications and synergy with other therapies.

Source: International Journal of Pharmaceutics

DOI: 10.1016/j.ijpharm.2025.125544

Authors: Behdad Delavari, Bahareh Bigdeli, Sepideh Khazeni, Pegah Varamini

Institutions: The University of Sydney, UNSW Sydney

Language: English

Topic: Nanoparticle-Based Drug Delivery

Subfield: Biomaterials

Field: Materials Science

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,650