Nanomaterial-Based Immunotherapy of Acute Myeloid Leukemia via Tumor Microenvironment Reshaping

Acute myeloid leukemia is a highly heterogeneous hematological malignancy. Its complex biological characteristics and significant immune escape ability lead to difficult clinical treatment and poor prognosis. Tumor microenvironment plays a key role in the occurrence and development of AML and the maintenance of immunosuppression and is an important target to improve the effect of immunotherapy. Nanoscale nanomaterials (typically 1–100 nm) offer a high interfacial area and tunable surface chemistry that enable programmable biodistribution, barrier penetration, and immune modulation, thereby reprogramming the tumor microenvironment to reverse immunosuppression and amplify antitumor immunity. Different from solid tumors, AML occurs in the special immune niche of bone marrow, and its bone marrow leukemia microenvironment significantly weakens the efficacy of immunotherapy through myeloid suppression, metabolic reprogramming, and abnormal expression of immune checkpoints. This review covers the characteristics of AML bone marrow microenvironment, summarizes the current AML immunotherapy models and limited mechanisms, and focuses on the path of nanomaterials to enhance the efficacy of immunotherapy through precise delivery, immune reprogramming, and microenvironment regulation. It also reviews the research progress of nanomaterials in the regulation of the AML microenvironment, focusing on the dual functions of their immunomodulators and drug delivery carriers and exploring their challenges in biosafety, targeting, and large-scale production, so as to provide ideas for AML immunotherapy and promote the clinical transformation of nanomedicines. Importantly, these nanoplatforms are particularly suited for bone marrow-niche-restricted applications in AML, such as minimal residual disease eradication, postremission maintenance, and relapse prevention, where localized immune reprogramming is needed with minimized systemic inflammation.