Nanotechnology-Based Synergistic Anticancer Drug Delivery and Neuromodulatory Effects: Preclinical and Clinical Insights

Abstract

Nanotechnology has revolutionized the field of cancer therapeutics by providing innovative strategies for targeted drug delivery, improved pharmacokinetics, and synergistic drug combinations that enhance therapeutic outcomes. In addition to their established role in oncology, emerging evidence suggests that nanoparticles may also modulate neuronal pathways, offering potential benefits in neuro-oncology as well as in reducing chemotherapy-induced neurotoxicity. In this study, we focused on the synergistic potential of doxorubicin (DOX) and paclitaxel (PTX) when co-loaded into a single nanoparticle (NP) platform designed for glioblastoma treatment.

We systematically evaluated the effects of dual-drug NPs on tumor cell cytotoxicity, neuronal signaling pathways, and in vivo tumor progression. Our findings demonstrate that DOX/PTX co-loaded nanoparticles exhibited markedly higher anticancer efficacy compared to free drug formulations and single-drug nanoparticle counterparts. Notably, the dual-drug NPs not only induced significant tumor cell apoptosis but also enhanced therapeutic selectivity by minimizing off-target toxicity. Furthermore, analysis of neuromodulatory outcomes revealed an upregulation of neuroprotective markers, suggesting that this delivery strategy may contribute to preserving neuronal function during chemotherapy.

In preclinical glioblastoma models, treatment with DOX/PTX-loaded nanoparticles resulted in robust tumor growth inhibition and prolonged survival, highlighting their translational potential for clinical applications. Taken together, these results underscore the dual advantage of nanotechnology-based co-delivery systems in simultaneously improving anticancer activity and mitigating neurological side effects. Our study provides compelling evidence that such nanoplatforms represent a promising avenue for advancing precision neuro-oncology and developing next-generation multimodal therapies