Manganese Dioxide-Entrapping Dendrimers Co-Deliver Protein and Nucleotide for Magnetic Resonance Imaging-Guided Chemodynamic/Starvation/Immune Therapy of Tumors

Gao, Yue; Ouyang, Zhijun; Shen, Siyan; Yu, Hongwei; Jia, Bingyang; Wang, Han; Shen, Mingwu; Shi, Xiangyang

doi:10.1021/acsnano.3c08174

Cited by 14 publications

(5 citation statements)

References 57 publications

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“…The results discussed thus far show the recovery effect of MNP@NcadAb treatment on IL-1β activated HUVEC (as a macrovascular model) and TGF-β activated HDMVEC (as a microvascular model). Considering that EndoMT in the context of atherosclerosis involves arterial (rather than venous) endothelial cells and considering the complexity of tumor microenvironments (i.e., multiple cytokines from cancer cells that could cause EndoMT), , we further extended our experiments to IL-1β activated human coronary artery endothelial cells (HCAEC) and cancer-cell conditioned medium activated HUVEC. This enabled us to evaluate the effect of MNP@NcadAb treatment on the whole spectrum of endothelial cells from capillaries, veins, and arteries activated by a diverse range of cytokines, as summarized in Figure A.…”

Section: Resultsmentioning

confidence: 99%

N-Cadherin Targeted Melanin Nanoparticles Reverse the Endothelial–Mesenchymal Transition in Vascular Endothelial Cells to Potentially Slow the Progression of Atherosclerosis and Cancer

Liu,

Yu,

Braucht

et al. 2024

ACS Nano

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Endothelial−mesenchymal transition (EndoMT) of vascular endothelial cells has recently been considered as a key player in the early progression of a variety of vascular and nonvascular diseases, including atherosclerosis, cancer, and organ fibrosis. However, current strategies attempting to identify pharmacological inhibitors to block the regulatory pathways of EndoMT suffer from poor selectivity, unwanted side effects, and a heterogeneous response from endothelial cells with different origins. Furthermore, EndoMT inhibitors focus on preventing EndoMT, leaving the endothelial cells that have already undergone EndoMT unresolved. Here, we report the design of a simple but powerful nanoparticle system (i.e., Ncadherin targeted melanin nanoparticles) to convert cytokineactivated, mesenchymal-like endothelial cells back to their original endothelial phenotype. We term this process "Reversed EndoMT" (R-EndoMT). R-EndoMT allows the impaired endothelial barriers to recover their quiescence and intactness, with significantly reduced leukocyte and cancer cell adhesion and transmigration, which could potentially stop atheromatous plaque formation and cancer metastasis in the early stages. R-EndoMT is achieved on different endothelial cell types originating from arteries, veins, and capillaries, independent of activating cytokines. We reveal that N-cadherin targeted melanin nanoparticles reverse EndoMT by downregulating an N-cadherin dependent RhoA activation pathway. Overall, this approach offers a different prospect to treat multiple EndoMT-associated diseases by designing nanoparticles to reverse the phenotypical transition of endothelial cells.

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Section: Resultsmentioning

confidence: 99%

N-Cadherin Targeted Melanin Nanoparticles Reverse the Endothelial–Mesenchymal Transition in Vascular Endothelial Cells to Potentially Slow the Progression of Atherosclerosis and Cancer

Liu,

Yu,

Braucht

et al. 2024

ACS Nano

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“…Nonetheless, Mn 2+ in various forms is approved by FDA as a clinical T1-weighted magnetic resonance imaging contrast agent ( 37 – 39 ). Numerous studies have also demonstrated that MnO 2 has a superior safety profile and biodegradable properties, suitable for biomedical applications ( 40 – 42 ). Second, considering the long-term recurrent nature of clinical UC manifestations, our study only provides a short-term evaluation of the in vivo efficacy against an acute UC model, limiting its clinical reference value for chromic UC diseases.…”

Section: Discussionmentioning

confidence: 99%

Oral microsphere formulation of M2 macrophage-mimetic Janus nanomotor for targeted therapy of ulcerative colitis

Luo,

Liu,

Cheng

et al. 2024

Sci. Adv.

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Oral medication for ulcerative colitis (UC) is often hindered by challenges such as inadequate accumulation, limited penetration of mucus barriers, and the intricate task of mitigating excessive ROS and inflammatory cytokines. Here, we present a strategy involving sodium alginate microspheres (SAMs) incorporating M2 macrophage membrane (M2M)–coated Janus nanomotors (denominated as Motor@M2M) for targeted treatment of UC. SAM provides a protective barrier, ensuring that Motor@M2M withstands the harsh gastric milieu and exhibits controlled release. M2M enhances the targeting precision of nanomotors to inflammatory tissues and acts as a decoy for the neutralization of inflammatory cytokines. Catalytic decomposition of H 2 O 2 by MnO 2 in the oxidative microenvironment generates O 2 bubbles, propelling Motor@M2M across the mucus barrier into inflamed colon tissues. Upon oral administration, Motor@M2M@SAM notably ameliorated UC severity, including inflammation mitigation, ROS scavenging, macrophage reprogramming, and restoration of the intestinal barrier and microbiota. Consequently, our investigation introduces a promising oral microsphere formulation of macrophage-biomimetic nanorobots, providing a promising approach for UC treatment.

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“…This multifunctional nanodelivery system amplified the cCAS-STING pathway activation of Mn 2+ and effectively promoted the maturation of immune cells. 89…”

Section: Anti-tumor Immunity Mechanism Of Mn-based Nps In Immunotherapymentioning

confidence: 99%

Manganese-based nanomaterials promote synergistic photo-immunotherapy: green synthesis, underlying mechanisms, and multiple applications

Cao,

Li,

Ren

et al. 2024

J. Mater. Chem. B

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Manganese Dioxide-Entrapping Dendrimers Co-Deliver Protein and Nucleotide for Magnetic Resonance Imaging-Guided Chemodynamic/Starvation/Immune Therapy of Tumors

Cited by 14 publications

References 57 publications

N-Cadherin Targeted Melanin Nanoparticles Reverse the Endothelial–Mesenchymal Transition in Vascular Endothelial Cells to Potentially Slow the Progression of Atherosclerosis and Cancer

N-Cadherin Targeted Melanin Nanoparticles Reverse the Endothelial–Mesenchymal Transition in Vascular Endothelial Cells to Potentially Slow the Progression of Atherosclerosis and Cancer

Oral microsphere formulation of M2 macrophage-mimetic Janus nanomotor for targeted therapy of ulcerative colitis

Manganese-based nanomaterials promote synergistic photo-immunotherapy: green synthesis, underlying mechanisms, and multiple applications

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