Janus Nanoparticles in Doxorubicin Delivery: A New Frontier in Targeted Cancer Treatment.

Cancer remains a primary global health challenge, accounting for millions of new cases and significant mortality annually. Although doxorubicin (DOX) is a fundamental anthracycline used for various malignancies, its therapeutic index is severely limited by poor selectivity, systemic toxicity, and dose-dependent cardiotoxicity. To address these issues, Janus nanoparticles (JNPs) have emerged as a promising bifunctional platform characterized by a structural asymmetry that allows for the independent functionalization of each hemisphere. This review examines primary fabrication routes-such as masking, microfluidics, self-assembly, and phase separation-and their specific applications in DOX delivery. The anisotropic architecture of JNPs enables a "separate rooms" concept, allowing for the co-delivery of incompatible drugs while facilitating multi-stimuli-responsive release mechanisms triggered by pH, enzymes, or NIR light. Furthermore, JNPs have demonstrated enhanced tumor accumulation and reduced systemic toxicity compared to conventional isotropic carriers. Recent developments even highlight the use of autonomous nanomotors to improve therapeutic delivery while minimizing premature leakage. However, clinical translation is currently hindered by manufacturing complexity, high equipment costs, scalability issues, and a lack of standardized reporting in the literature. Ultimately, JNPs represent a sophisticated frontier in precision oncology, though robust manufacturing processes and characterization protocols are required for future medical adoption.