Tumor-selective catalytic nanomedicine by nanocatalyst delivery

Huo, Minfeng; Wang, Liying; Chen, Yu; Shi, Jianlin

doi:10.1038/s41467-017-00424-8

Cited by 1,179 publications

(896 citation statements)

References 39 publications

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“…Amorphous silica, whose long-range formula is SiO2, consists of tetraoxosilicon centres (denoted Q for quadrifunctional) interlinked by siloxane bonds. 21 A fully condensed Si centre (Q 4 , being linked to 4 other centres) can only exist in the core of a particle, whereas partially condensed centres (Q 2 or Q 3 ) are associated with the surface. USSN accounted for most (84  3%) of the silicon content in the dispersion and, of this, 43% was partially condensed (Q 2 & Q 3 ) and 57% was fully condensed (Q 4 ).…”

Section: Resultsmentioning

confidence: 99%

Non-Functionalized Ultrasmall Silica Nanoparticles Directly and Size-Selectively Activate T Cells

et al. 2018

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Sub-micron sized silica nanoparticles, even as small as 10-20 nm in diameter, are well known for their activation of mononuclear phagocytes. In contrast, the cellular impact of those < 10 nm (i.e., ultrasmall silica nanoparticles (USSN)) is not well established for any cell type despite anticipated human exposure.Here, we synthesized discrete populations of USSN, with volume median diameters between 1.8 to 16 nm, and investigated their impact on the mixed cell population of human primary peripheral mononuclear cells. USSN of 1.8-7.6 nm diameter, optimally 3.6-5.1 nm diameter, induced dose-dependent CD4 and CD8 T cell activation in terms of cell surface CD25 and CD69 upregulation at concentrations above 150 M SiTOTAL (~500 nM particles). Induced activation with only ~2.4 M particles was (a) equivalent to that observed with typical positive control levels of Staphylococcal enterotoxin B (SEB) and (b) evident in antigen presenting cell-deplete cultures as well as in a pure T cell line (Jurkat) culture. In the primary mixed cell population, USSN induced IFN-secretion but failed to induce T cell proliferation or secretion of IL-2, IL-10, or IL-4. Collectively, these data indicate that USSN initiate activation, with Th1-polarisation, of T cells via direct particle-cell interaction. Finally, similarly sized iron hydroxide particles did not induce expression of T cell activation markers, indicating some selectivity of the ultrasmall particle type. Given that humans may be exposed to ultrasmall particles, and that these materials have emerging bio-clinical applications, their off-target immunomodulatory effects via direct T cell activation should be carefully considered.

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Section: Resultsmentioning

confidence: 99%

Non-Functionalized Ultrasmall Silica Nanoparticles Directly and Size-Selectively Activate T Cells

et al. 2018

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“…Thus, cancer cells are more sensitive to further enhanced oxidative stress beyond the cellular tolerability threshold 2 . On this basis, ROS-mediated therapies, such as photodynamic therapy (PDT) [3][4][5][6] and chemodynamic therapy (CDT) [7][8][9][10][11] , are developed to disrupt the cellular self-adaptation mechanisms and induce cell death based on ROS-generating agents 12 .…”

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confidence: 99%

An open source and reduce expenditure ROS generation strategy for chemodynamic/photodynamic synergistic therapy

et al. 2020

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The therapeutic effect of reactive oxygen species (ROS)-involved cancer therapies is significantly limited by shortage of oxy-substrates, such as hypoxia in photodynamic therapy (PDT) and insufficient hydrogen peroxide (H 2 O 2 ) in chemodynamic therapy (CDT). Here, we report a H 2 O 2 /O 2 self-supplying nanoagent, (MSNs@CaO 2 -ICG)@LA, which consists of manganese silicate (MSN)-supported calcium peroxide (CaO 2 ) and indocyanine green (ICG) with further surface modification of phase-change material lauric acid (LA). Under laser irradiation, ICG simultaneously generates singlet oxygen and emits heat to melt the LA. The exposed CaO 2 reacts with water to produce O 2 and H 2 O 2 for hypoxia-relieved ICG-mediated PDT and H 2 O 2 -supplying MSN-based CDT, acting as an open source strategy for ROS production. Additionally, the MSNs-induced glutathione depletion protects ROS from scavenging, termed reduce expenditure. This open source and reduce expenditure strategy is effective in inhibiting tumor growth both in vitro and in vivo, and significantly improves ROS generation efficiency from multi-level for ROS-involved cancer therapies.

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“…[23] Moreover, under the intracellular superoxide dismutase (SOD)mediated disproportionation reactions, O 2 −• molecule further converts to hydrogen peroxide (H 2 O 2 ) and O 2 . [27,28] Remarkably, O 2 is partially recyclable during this cascade reaction and valuable to ameliorate the hypoxia microenvironment for enhanced PDT efficacy. [27,28] Remarkably, O 2 is partially recyclable during this cascade reaction and valuable to ameliorate the hypoxia microenvironment for enhanced PDT efficacy.…”

Section: Doi: 101002/advs201900530mentioning

confidence: 99%

A Bacteriochlorin‐Based Metal–Organic Framework Nanosheet Superoxide Radical Generator for Photoacoustic Imaging‐Guided Highly Efficient Photodynamic Therapy

et al. 2019

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Hypoxic tumor microenvironment is the bottleneck of the conventional photodynamic therapy (PDT) and significantly weakens the overall therapeutic efficiency. Herein, versatile metal–organic framework (MOF) nanosheets (DBBC‐UiO) comprised of bacteriochlorin ligand and Hf 6 (µ 3 ‐O) 4 (µ 3 ‐OH) 4 clusters to address this tricky issue are designed. The resulting DBBC‐UiO enables numerous superoxide anion radical (O 2 −• ) generation via a type I mechanism with a 750 nm NIR‐laser irradiation, part of which transforms to high toxic hydroxyl radical (OH•) and oxygen (O 2 ) through superoxide dismutase (SOD)‐mediated catalytic reactions under severe hypoxic microenvironment (2% O 2 ), and the partial recycled O 2 enhances O 2 −• generation. Owing to the synergistic radicals, it realizes advanced antitumor performance with 91% cell mortality against cancer cells in vitro, and highly efficient hypoxic solid tumor ablation in vivo. It also accomplishes photoacoustic imaging (PAI) for cancer diagnosis. This DBBC‐UiO, taking advantage of superb penetration depth of the 750 nm laser and distinct antihypoxia activities, offers new opportunities for PDT against clinically hypoxic cancer.

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Tumor-selective catalytic nanomedicine by nanocatalyst delivery

Cited by 1,179 publications

References 39 publications

Non-Functionalized Ultrasmall Silica Nanoparticles Directly and Size-Selectively Activate T Cells

Non-Functionalized Ultrasmall Silica Nanoparticles Directly and Size-Selectively Activate T Cells

An open source and reduce expenditure ROS generation strategy for chemodynamic/photodynamic synergistic therapy

A Bacteriochlorin‐Based Metal–Organic Framework Nanosheet Superoxide Radical Generator for Photoacoustic Imaging‐Guided Highly Efficient Photodynamic Therapy

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