Targeting nano-regulator based on metal–organic frameworks for enhanced immunotherapy of bone metastatic prostate cancer

Abstract

Bone metastasis is the main cause of death in patients with prostate cancer (PCa), but there lacks effective treatment method. Immunotherapy shows new hopes for bone metastatic PCa patients, while the efficacy is still unsatisfactory and limited by the unique immunosuppressive microenvironment in metastatic bone site. Here, we developed a bone-targeted nano-delivery system as a nano-regulator to enhance the immunotherapy of bone metastatic PCa. The nanosystem was assembled via coordination between phytic acid (PA) and Fe3+ to form nano-sized metal–organic framework (MOF), through which mitoxantrone (MTO) was encapsulated. At cellular level, the nanosystem showed selective cytotoxicity towards RM-1 PCa cells over immune cells, and could induce tumor cells immunogenic cell death (ICD) to improve the immunogenicity of the tumor. Moreover, the nanosystem was able to induce ubiquitination of TGFβ receptor (TβR) on immune cells to promote its degradation, thus serving as a nano-regulator to block the functions of TGF-β, an abundant cytokine that has a systematically immunosuppressive effect in the tumor microenvironment. Upon intravenous injection, the nanoparticle showed pro-longed blood circulation and targeting accumulation into bone metastatic site, and imposed robust anti-tumor effect in combination with αCTLA-4. In addition, bone destruction was significantly alleviated after treatment to reduce the skeletal-related events. Overall, this work provides a biocompatible nanomedicine to restore immune sensitivity of bone metastatic tumor for enhanced immunotherapy by blocking TGF-β signaling pathway.

Point biserial correlation symbiotic organism search nanoengineering based drug delivery for tumor diagnosis

“…Mn-based cGAS-STING activation was developed in 27 for increasing the sensitivity. Bone-targeted nano-delivery system was utilized in 28 with higher immunotherapy. Green-synthesized Ag and Cu-doped Bismuth oxide nanoparticles were designed in 29 for biomedical advancements.…”

Beyond boundaries: unraveling innovative approaches to combat bone-metastatic cancers

“…A bone-targeted nano-delivery system, referred to as a nano-regulator, was developed to enhance immunotherapy in this specific context. The researchers assembled the nano-regulator using phytic acid (PA) and Fe3 + to create a nano-sized metal-organic framework (MOF) ( 160 ). They then encapsulated mitoxantrone (MTO), a chemotherapy drug, within this framework.…”

“…Additionally, the treatment significantly alleviated bone destruction, reducing skeletal-related events associated with bone metastasis ( 160 ). This study provides a biocompatible nanomedicine approach that shows potential for enhancing immunotherapy in bone metastatic prostate cancer.…”

Self-Assembled Nanobiomaterials for Combination Immunotherapy

“…Microporous materials possessing interpenetrated apertures and pores with dimensions less than 2 nm have shown significant potential as drug delivery systems due to their high surface area to volume ratio. The two promising classes of microporous materials, which are continuously evolving for cancer therapeutics, are metal organic frameworks (MOFs) and covalent–organic frameworks (COFs). − …”

“…MOFs are materials self-assembled from small organic ligands and metal nodes. , While they are highly stable under extreme mechanical and thermal conditions, their degradation under specific physiological cues such as acidic pH enables controlled release of cargo at a specific site of action. This degradation also can be strategized to utilize the immune modulating properties of metal ions in the treatment of diseases in combination with the other therapeutic regimens such as PTT and CT. Metal ions such as calcium (Ca 2+ ), zinc (Zn 2+ ), potassium (K + ), and nickel (Ni 2+ ) tend to show notable effects on T- and B-cell maturation, as well as the release of inflammatory cytokines leading to ICD of the tumor cells. − Several MOF candidates have been explored for combinatorial immunotherapy with promising results. ,,− …”