Advances in Nanotechnology for Lymphoma Treatment: Targeted Delivery, Immunomodulation, and TME-Responsive Therapy Strategies.

Lymphoma is a heterogeneous malignant proliferative disease of lymphocytes, with characteristics of liquid tumor and solid tumor. With the emergence of targeted drugs, monoclonal antibodies, bispecific antibodies, antibody-drug conjugates, and CAR-T therapy, the treatment landscape for lymphoma has been transformed. However, these therapies also possess limitations such as short plasma circulation time, low bioavailability, the development of drug resistance, and dose-dependent toxicity. With the advancement of nanotechnology, nanotech-based targeted delivery systems enable tumor-specific targeting and reduce off-target toxicity. Nano-immunotherapeutic systems, such as nanobody-based CAR-T therapy and mRNA-LNP nanovaccines, address limitations like drug resistance and relapse caused by antigen escape, inducing long-term anti-tumor immunity. Furthermore, smart designs responsive to the tumor microenvironment (TME) can significantly enhance drug accumulation and release efficiency at the lesion site. Innovative nanotech-based therapies are progressively transitioning from the laboratory to the clinic. By designing targeted nanocarriers, nano-immunotherapies, and TME-responsive intelligent nanotherapeutic platforms, targeted delivery of anti-lymphoma drugs can be achieved, enhancing efficacy and reducing toxicity. Simultaneously, these platforms can integrate multiple therapeutic modalities (such as chemodynamic therapy, immunomodulation, and gene silencing) to achieve synergistic and enhanced anti-lymphoma effects, offering new paradigms for lymphoma treatment.