Synergistic innovations of nanomedicine in lymphoma treatment: a systematic review.

Lymphoma therapy faces persistent challenges, including tumor heterogeneity, drug resistance, and immunosuppressive microenvironments, particularly in relapsed or refractory cases. Current treatments, such as chemotherapy, targeted therapy, and cell-based therapies, are limited by suboptimal targeting, systemic toxicity, and manufacturing complexities, highlighting the urgent need for innovative solutions. Nanomedicine has emerged as a transformative approach, integrating material design with therapeutic strategies to address these barriers. This review of 133 preclinical studies highlights key advancements: the dominance of lipid- and polymer-based nanoparticles, increasing use of natural materials, and the combination of passive EPR-based targeting with active strategies like CD20-mediated approaches. Stimuli-responsive systems, particularly pH-sensitive platforms, further enhance precision drug delivery, improving efficacy while reducing toxicity. Artificial intelligence accelerates progress by integrating multi-omics data and utilizing machine learning to optimize nanoparticle design, enhancing precision and personalization. Additionally, nanotechnology has advanced imaging, minimized chemotherapy-induced toxicity, and enabled in vivo CAR-T generation, offering safer and scalable therapeutic options. However, clinical translation faces hurdles, including scalable manufacturing, single-cell omics-guided nanoparticle design, and humanized models to validate immune microenvironment interactions. Addressing these challenges is essential to fully realize the potential of nanomedicine and AI integration, driving next-generation platforms for precision lymphoma therapy.