Reversing the negative effect of adenosine A1 receptor-targeted immunometabolism modulation on melanoma by a co-delivery nanomedicine for self-activation of anti-PD-L1 DNAzyme

Guo, Jia; Liu, Peng; Wei, Benliang; Peng, Ying; Ding, Jinsong; Zhang, Hailun; Zhang, Guanxiong; Su, Juan; Liu, Hong; Zhou, Wenhu; Chen, Xiang

doi:10.1016/j.nantod.2022.101722

Cited by 18 publications

(12 citation statements)

References 57 publications

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“…S1), the nanoparticles showed core-shell structures, in which the hydrophobic MTO was loaded into nanocore with the shell layer of PA/Fe 3+ MOF for stabilization. This result was consistent with our previous work to use MOF for hydrophobic drug loading (Guo et al 2023;Liu et al 2020). We also noticed that the particle size observed by TEM was significantly smaller than that of hydrodynamic size, which can be attributable to nanoparticle dehydration before TEM measurement.…”

Section: Resultssupporting

confidence: 92%

“…The coordination ratio of PA/ Fe 3+ was optimized to be 2/1 (w/w) (Additional file 1: Table S1), and the resulting PA/Fe 3+ MOF displayed a dynamic size ~ 146 nm with PDI of 0.155. We then used such MOF nanoparticles for MTO loading based on our previous reports (Guo et al 2023;Wang et al 2022). Interestingly, the feeding MTO concentration has little effect on drug loading efficiency, but affected particle size significantly (Additional file 1: Table S2), and the smallest size of MTO@PA/Fe 3+ MOF was obtained at 0.125 mg/ mL (135 nm, PDI = 0.002) (Fig.…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2023

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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.

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Section: Resultssupporting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

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

et al. 2023

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“…We then used such MOF nanoparticles for MTO loading based on our previous reports. 15,16 Interestingly, the feeding MTO concentration has little effect on drug loading e ciency, but affected particle size signi cantly (Table S2), and the smallest size of MTO@PA/Fe 3+ MOF was obtained at 0.125 mg/ml (135 nm, PDI = 0.002) (Fig. 1B).…”

Section: Resultsmentioning

confidence: 99%

Targeting Nano-regulator based on Metal-Organic Frameworks for Enhanced Immunotherapy of Bone Metastatic Prostate Cancer

Huang

Yuan

Xie

et al. 2023

Preprint

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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.

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“…A nanoparticle-polymer network prepared using ROS-consuming bond-bridged copolymers with bromodomain-containing protein 4 inhibitor JQ1 (DHCRJ) reduced ROS in tumor cells, reduced glucose uptake for lactate production and facilitated tumor suppression in triple-negative breast cancer [ 77 ]. A different nanosystem with 8-Cyclopentyl-1, 3-propylxanthine (DPCPX) (adenosine A1 receptor inhibitor)-encapsulated nanoparticles with PLGA cores and metal-organic-framework shells (with Fe3+/Mn2+–tannic acid) facilitated tumor suppression through the co-inhibition of adenosine A1 receptor and PD-L1 DNAzyme and enhanced dendritic-cell and T-cell responses for anti-tumor activity [ 78 ]. Mitochondria-targeting nanomedicine approaches have also been explored for the treatment of human diseases.…”

Section: Challenges and Future Perspectivesmentioning

confidence: 99%

A Current Perspective on the Potential of Nanomedicine for Anti-Tuberculosis Therapy

et al. 2023

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Tuberculosis (TB) is one of the ten infectious diseases that cause the highest amount of human mortality and morbidity. This infection, which is caused by a single pathogen, Mycobacterium tuberculosis, kills over a million people every year. There is an emerging problem of antimicrobial resistance in TB that needs urgent treatment and management. Tuberculosis treatment is complicated by its complex drug regimen, its lengthy duration and the serious side-effects caused by the drugs required. There are a number of critical issues around drug delivery and subsequent intracellular bacterial clearance. Drugs have a short lifespan in systemic circulation, which limits their activity. Nanomedicine in TB is an emerging research area which offers the potential of effective drug delivery using nanoparticles and a reduction in drug doses and side-effects to improve patient compliance with the treatment and enhance their recovery. Here, we provide a minireview of anti-TB treatment, research progress on nanomedicine and the prospects for future applications in developing innovative therapies.

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Reversing the negative effect of adenosine A1 receptor-targeted immunometabolism modulation on melanoma by a co-delivery nanomedicine for self-activation of anti-PD-L1 DNAzyme

Cited by 18 publications

References 57 publications

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

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

Targeting Nano-regulator based on Metal-Organic Frameworks for Enhanced Immunotherapy of Bone Metastatic Prostate Cancer

A Current Perspective on the Potential of Nanomedicine for Anti-Tuberculosis Therapy

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