Openwork@Dendritic Mesoporous Silica Nanoparticles for Lactate Depletion and Tumor Microenvironment Regulation

Tang, Jie; Meka, Anand Kumar; Theivendran, Shevanuja; Wang, Yue; Yang, Yannan; Song, Hao; Fu, Joseph; Ban, Wenhuang; Gu, Zhengying; Lei, Chang; Li, Shumin; Yu, Chengzhong

doi:10.1002/ange.202001469

Cited by 29 publications

(18 citation statements)

References 40 publications

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“…1i) was observed at 24 h. The tumor accumulation may bene t from the EPR effect of nanocomposites. Our previous experiment found that mice injected with free LOD died within 48 h. This phenomenon was also found by Tang [24]. The quick diffusion in blood and distribution in organs of free LOD may account for the phenomenon.…”

Section: Resultssupporting

confidence: 66%

GSH-responsive Nanoplatform for Intra/Extracellular Lactate Exhaustion to Enhance Antitumor Immunotherapy

Tan

Huang

Zhang

et al. 2022

Preprint

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Background Immune checkpoint blockade (ICB) therapies have reshaped tumor treatment by activating the antitumor immune response. However, the antitumor effect of ICB is seriously restricted by the immunosuppressive tumor microenvironment (ITM). A variety of strategies to alleviate the ITM have been investigated. Direct regulation of lactate metabolism in tumor microenvironment holds promise for ITM modulation. Results Glutathione (GSH) -responsive hollow mesoporous organosilicon (HMOP) was successfully fabricated, with monocarboxylate transporter 1/4 inhibitor (diclofenac, DC) and lactate oxidase (LOD) were loaded in/onto the HMOP (designed as DC-HMOP-LOD). DC-HMOP-LOD could spontaneously be biodegraded in tumor microenvironment due to disulfide bonds, and then DC/LOD could be released to exhaust intra/extracellular lactate. Consequently, lactate depletion induced an immunocompetent tumor microenvironment by activating immune-promoting cells including dendritic cells, CD4+ T cells, CD8+ T cells, and natural killer cells, and inactivating immunosuppressive cells containing tumor-associated macrophages and myeloid-derived suppressor cells, ultimately strengthening the antitumor effect of ICB therapy. Conclusion DC-HMOP-LOD effectively hindered the transmission of lactate and directly oxidized lactate, collaboratively depleting lactate in the TME. The synergetic depletion reversed the ITM and could improve the antitumor effects of aPD1-based immunotherapy.

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Section: Resultssupporting

confidence: 66%

GSH-responsive Nanoplatform for Intra/Extracellular Lactate Exhaustion to Enhance Antitumor Immunotherapy

Tan

Huang

Zhang

et al. 2022

Preprint

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“…Enzyme-based nanomotors is one of the most typical chemical-fuel-driven nanomotors, which can generate a strong driving force to overcome random Brownian motion for efficient self-propulsion, relying on high efficient biocatalytic reactions of inherent biofuels in natural biological hosts. − Owing to the highly specific enzyme-catalyzed reactions, the enzyme-based nanomotors show a very high selectivity to biofuels, which enables them to be driven only in specific physiological environment. − Additionally, because the biological system can continuously generate the biofuel, the nanomotors are able to get a constant driving force for the long-lasting self-propulsion. Due to these unique properties and superior biocompatibility, a series of enzyme-based nanomotors have been developed, such as the urea-powered mesoporous silica nanoparticles (based on urease), glucose-powered stomatocyte-shaped polymer nanoparticles (based on glucose oxidase), the l -arginine-powered hyperbranched polymer nanospheres (based on NO synthase), triacetin mesoporous silica nanoparticles (based on lipase), etc. − …”

Section: Introductionmentioning

confidence: 99%

Enzyme-Based Mesoporous Nanomotors with Near-Infrared Optical Brakes

et al. 2022

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As one of the most important parameters of the nanomotors’ motion, precise speed control of enzyme-based nanomotors is highly desirable in many bioapplications. However, owing to the stable physiological environment, it is still very difficult to in situ manipulate the motion of the enzyme-based nanomotors. Herein, inspired by the brakes on vehicles, the near-infrared (NIR) “optical brakes” are introduced in the glucose-driven enzyme-based mesoporous nanomotors to realize remote speed regulation for the first time. The novel nanomotors are rationally designed and fabricated based on the Janus mesoporous nanostructure, which consists of the SiO2@Au core@shell nanospheres and the enzymes-modified periodic mesoporous organosilicas (PMOs). The nanomotor can be driven by the biofuel of glucose under the catalysis of enzymes (glucose oxidase/catalase) on the PMO domain. Meanwhile, the Au nanoshell at the SiO2@Au domain enables the generation of the local thermal gradient under the NIR light irradiation, driving the nanomotor by thermophoresis. Taking advantage of the unique Janus nanostructure, the directions of the driving force induced by enzyme catalysis and the thermophoretic force induced by NIR photothermal effect are opposite. Therefore, with the NIR optical speed regulators, the glucose-driven nanomotors can achieve remote speed manipulation from 3.46 to 6.49 μm/s (9.9–18.5 body-length/s) at the fixed glucose concentration, even after covering with a biological tissue. As a proof of concept, the cellar uptake of the such mesoporous nanomotors can be remotely regulated (57.5–109 μg/mg), which offers great potential for designing smart active drug delivery systems based on the mesoporous frameworks of this novel nanomotor.

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“…(23)(24)(25). However, the composition of the obtained dendritic mesoporous nanoparticles is limited to SiO 2 , dopamine, resorcinol formaldehyde, Au, Pd, Pt, and Al 2 O 3 (26)(27)(28)(29)(30)(31)(32). The mesostructure of the reported porous rare earth-based materials is disordered, and its structural parameters are difficult to be regulated (33,34).…”

Section: Introductionmentioning

confidence: 99%

Versatile synthesis of dendritic mesoporous rare earth–based nanoparticles

Wang

Liu

et al. 2022

Sci. Adv.

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Rare earth–based nanomaterials that have abundant optical, magnetic, and catalytic characteristics have many applications. The controllable introduction of mesoporous channels can further enhance its performance, such as exposing more active sites of rare earth and improving the loading capacity, yet remains a challenge. Here, we report a universal viscosity-mediated assembly strategy and successfully endowed rare earth–based nanoparticles with central divergent dendritic mesopores. More than 40 kinds of dendritic mesoporous rare earth–based (DM-REX) nanoparticles with desired composition (single or multiple rare earth elements, high-entropy compounds, etc.), particle diameter (80 to 500 nanometers), pore size (3 to 20 nanometers), phase (amorphous hydroxides, crystalline oxides, and fluorides), and architecture were synthesized. Theoretically, a DM-REX nanoparticle library with 393,213 kinds of possible combinations can be constructed on the basis of this versatile method, which provides a very broad platform for the application of rare earth–based nanomaterials with rational designed functions and structures.

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Openwork@Dendritic Mesoporous Silica Nanoparticles for Lactate Depletion and Tumor Microenvironment Regulation

Cited by 29 publications

References 40 publications

GSH-responsive Nanoplatform for Intra/Extracellular Lactate Exhaustion to Enhance Antitumor Immunotherapy

GSH-responsive Nanoplatform for Intra/Extracellular Lactate Exhaustion to Enhance Antitumor Immunotherapy

Enzyme-Based Mesoporous Nanomotors with Near-Infrared Optical Brakes

Versatile synthesis of dendritic mesoporous rare earth–based nanoparticles

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