Bioengineered Exosome-Magnetic Nanoplatform for Precision Therapy of Hepatocellular Carcinoma via Dual-Targeted Drug...

Hepatocellular carcinoma (HCC) continues to pose a significant threat to global health, contributing substantially to worldwide cancer-related mortality, particularly in high-incidence regions such as Asia, where current treatment strategies are often limited by poor drug delivery efficiency, systemic toxicity, and drug resistance.

To address these critical challenges, we developed an innovative dual-targeted nanoplatform (Exo-SPIONs-SRF/CGA) that synergistically combines the natural tumour-homing capability of HCC-derived exosomes with the magnetic guidance of superparamagnetic iron oxide nanoparticles (SPIONs) for precision drug targeting. This nanoplatform co-encapsulates SRF and CGA to improve the therapeutic index by enhancing desired responses and minimizing undesired side effects.

The exosome component provides inherent biological targeting to HCC cells. At the same time, the incorporated SPIONs enable external magnetic field-guided spatial control, collectively ensuring superior tumour accumulation compared to conventional delivery systems. Furthermore, the platform's tumour microenvironment-responsive release characteristics ensure localized drug activation, maximizing the therapeutic index through spatial and temporal control of drug availability. In vitro and in vivo evaluations demonstrated that this nanoplatform significantly enhances tumour suppression and drug retention while reducing systemic side effects compared to monotherapies or single-modality nanocarriers.

The Exo-SPIONs-SRF/CGA platform represents a promising strategy in HCC treatment, addressing fundamental limitations of current therapies by simultaneously overcoming biological barriers to drug delivery, enhancing therapeutic efficacy through synergistic drug combinations, and minimizing collateral damage to healthy tissues, thereby advancing the frontier of precision oncology toward more effective and safer HCC management.