In July 2024, the research team led by Professors Gu Yueqing and Li Siwen from the School of Engineering at our university published a paper titled “A Bispecific Nanosystem Activates Endogenous NK Cells in the Bone Marrow for Hematologic Malignancies Therapy” in Nature Nanotechnology. This paper presents the development of a bispecific nanovesicle system with bone marrow-targeting capabilities for the treatment and prevention of hematologic malignancies.
Hematologic malignancies are primarily caused by the uncontrolled clonal proliferation of tumor cells in the bone marrow, leading to extremely high mortality and recurrence rates. While current treatments such as chemotherapy, immunotherapy, and cellular therapy have shown promise in extending patient survival, they face limitations due to the lack of effective bone marrow targeting and the challenge of reversing the bone marrow microenvironment. These limitations hinder the ability to specifically eliminate tumor cells in the bone marrow, reduce toxic side effects, and prevent disease relapse.
In this study, the research team employed hematopoietic stem cell-derived nanovesicles (Hn) as bone marrow-targeting carriers, modified with dual ligands (aPD-L1 and aNKG2D) and encapsulating colony-stimulating factor (CSF). This bispecific drug-loaded nanovesicle system CSF@E-Hn exhibited excellent bone marrow-targeting capabilities in vivo. It effectively captured both tumor cells and NK cells, while simultaneously activating NK cells to efficiently clear tumor cells from the bone marrow. In mouse models of acute myeloid leukemia (AML) and multiple myeloma (MM), CSF@E-Hn demonstrated remarkable therapeutic efficacy.
Additionally, CSF@E-Hn was found to elicit an immune memory effect after entering the bone marrow, providing protection against tumor recurrence following the initial tumor clearance. It also promoted the differentiation of undifferentiated hematopoietic stem cells into hematopoietic and immune cells. By disrupting osteoclast production and promoting osteoblast formation, the system maintained bone homeostasis, improved the bone marrow microenvironment, and helped prevent disease relapse, thereby establishing a long-lasting protective mechanism.
The bispecific nanovesicle drug delivery system CSF@E-Hn exhibits excellent biocompatibility and reduced toxicity, offering vast clinical potential in both the treatment and prevention of hematologic malignancies.
Fig. 1 Construction and therapeutic mechanism of CSF@E-Hn
