Folate receptor-targeted nanocarrier delivery of noscapinoids for breast cancer therapy

Introduction: Breast cancer remains the most prevalent malignancy among women, accounting for ~6.9% of cancer-related deaths annually, affecting 1 in 100 women. The fear of needles and the adverse effects of the current chemotherapeutics, the present study explores folate receptor-targeted delivery of noscapinoid-loaded PLGA-PEG-Folate (PPF) nanoparticles as a potential approach for breast cancer therapy.

Methods: A series of noscapine derivatives were rationally designed using in silico approaches and chemically synthesized. Leveraging the overexpression of folate receptors on breast cancer cells, noscapinoid-loaded PPF nanoparticles were developed to enhance systemic circulation and target specificity. These nanoparticles were characterized for drug loading efficiency, encapsulation, and release kinetics. In vitro studies assessed their anti-proliferative and pro-apoptotic effects in breast cancer cell lines. Further, in vivo efficacy was evaluated using a xenograft mouse model, focusing on tumour regression, apoptosis induction, and biodistribution. Toxicity profiles were assessed via histopathological and haematological analyses.

Result: The PPF-conjugated noscapinoid nanoparticles demonstrated sustained drug release and significantly greater inhibition of breast cancer cell proliferation compared to free drugs. In vivo, the targeted nanocarriers effectively reduced tumour burden, likely due to enhanced uptake via folate receptor-mediated endocytosis. Although the precise mechanism of tumour regression remains under investigation, folate-functionalization proved critical for selective delivery and therapeutic efficacy. The formulation also exhibited minimal systemic toxicity, supporting its potential as a targeted treatment for breast cancer.

Discussion: The folate-targeted PPF-noscapinoid nanoparticles demonstrated enhanced anti-tumour efficacy and selective delivery to breast cancer cells, reducing off-target effects. These findings support their potential as a promising, less toxic alternative to conventional chemotherapy.

Eeshara Naik is a Research Scholar and currently working as a Senior Research Fellow (SRF). Her research focuses on cancer therapy through receptor-mediated drug delivery, with particular emphasis on the development of targeted nanocarrier-based therapeutic approaches for cancer treatment. She was awarded a Gold Medal during her M.Sc. for academic excellence. She has also contributed as a co-author to five research publications in the field of cancer research and drug delivery. She also received a Best Poster Award at an International Conference held at IIIT Roorkee in 2025. Her research interests focus on developing targeted and efficient drug-delivery strategies to improve the therapeutic potential of anticancer agents while enhancing their specificity toward cancer cells.