Conspectus Silica-based nanoparticles (SNPs) are a classic type of material employed in biomedical applications because of their excellent biocompatibility and tailorable physiochemical properties. ...Typically, SNPs are designed as nanocarriers for therapeutics delivery, which can address a number of intrinsic drawbacks of therapeutics, including limited bioavailability, short circulation lifetime, and unfavorable biodistribution. To improve the delivery efficiency and spatiotemporal precision, tremendous efforts have been devoted to engineering the physiochemical properties of SNPs, including particle size, morphology, and mesostructure, as well as conjugating targeting ligands and/or “gatekeepers” to endow improved cell selectivity and on demand release profiles. Despite significant progress, the biologically inert nature of the bare silica framework has largely restricted the functionalities of SNPs, rendering conventional SNPs mainly as nanocarriers for targeted delivery and controlled release. To meet the requirements of next generation nanomedicines with improved efficacy and precision, new insights on the relationship between the physiochemical properties of SNPs and their biological behavior are highly valuable. Meanwhile, a conceptual shift from a simple spatiotemporal control mechanism to a more sophisticated biochemistry and signaling pathway modulation would be of great importance. In this Account, an overview of our recent contribution to the field is presented, wherein SNPs with rationally designed nanostructures and nanochemistry are applied as nanocarriers (defined as “nanomaterials being used as a transport module for another substance” according to Wikipedia) and/or biomodulators (defined as “any material that modifies a biological response” according to Wiktionary). This Account encompasses two main sections. In the first section, we focus on the conventional nanocarriers concept with new insights on the design principles of the nanostructures. We present examples to demonstrate the engineering of pore geometry, surface topology, and asymmetry of nanoparticles to achieve enhanced drug, gene, and protein delivery efficiency. The contribution of surface roughness of SNPs on improving the cellular uptake efficiency, adhesion property, and DNA transfection capacity is particularly highlighted. In the second section, we discuss novel SNPs designed as biomodulators to regulate intracellular microenvironment and cell signaling, such as the oxidative stress and glutathione levels for improving the anticancer efficacy of therapeutics and mRNA transfection in specific cell lines. The interplay between the nanoparticles, biological system, and drugs is discussed. We further discuss how to engineer the composition of SNPs to modulate metal hemostasis to realize inherent anticancer activity. Two typical examples, including modulating copper signaling for tumor vasculature targeted therapy and controlling iron signaling for macrophage polarization based immunotherapy, are presented to highlight the unique advantages of SNPs as nanosized therapeutics in comparison to molecular drugs. Moreover, utilizing these two examples, we showcase the possibility of designing SNPs with intrinsic pharmaceutical activity to indirectly control tumor growth without inducing significant cytotoxicity, thus alleviating the biosafety concerns of nanomedicines. At the end of this Account, we discuss our personal perspectives on the promises, opportunities, and issues in engineered SNPs as nanocarriers as well as their transition toward biomodulators. With a major focus on the latter scenario, the current status and possible future directions are outlined.
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IJS, KILJ, NUK, PNG, UL, UM
Abstract Targeted delivery of anticancer drug specifically to tumor site without damaging normal tissues has been the dream of all scientists fighting against cancer for decades. Recent breakthrough ...on nanotechnology based medicines has provided a possible tool to solve this puzzle. Among diverse nanomaterials that are under development and extensive study, silica based nanoparticles with vast advantages have attracted great attention. In this review, we concentrate on the recent progress using silica based nanoparticles, particularly mesoporous silica nanoparticles (MSNs), for targeted drug delivery applications. First, we discuss the passive targeting capability of silica based nanoparticles in relation to their physiochemical properties. Then, we focus on the recent advances of active targeting strategies involving tumor cell targeting, vascular targeting, nuclear targeting and multistage targeting, followed by an introduction to magnetic field directed targeting approach. We conclude with our personal perspectives on the remaining challenges and the possible future directions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Introducing mRNA into cells has attracted intense interest for diverse applications; however, success requires delivery solutions. Engineered nanomaterials have been applied as mRNA nanocarriers; ...their functions are designed mainly as delivery vehicles, but rarely in regulation of the protein translation. Recently, progress in nanobiotechnology has shifted the design principle of mRNA nanocarriers from simple delivery tools to translation modulators. Here, we review the emerging concepts of nanomaterials regulating mRNA translation and recent progress in mRNA delivery. Designer nanomaterials providing integrated functions for specific mRNA applications are also reviewed to provide insights for the design of next‐generation nanomaterials to revolutionize mRNA technology.
Emerging concepts for nanomaterials regulating mRNA translation and recent progress in mRNA delivery are discussed in this Minireview. Designer nanomaterials with integrated functions for specific mRNA applications are also reviewed to provide insights for the design of next‐generation nanomaterials to revolutionize mRNA technology.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Assembly of different metal-organic framework (MOF) building blocks into hybrid MOF-on-MOF heterostructures is promising in chemistry and materials science, however the development of ternary ...MOF-on-MOF heterostructures with controllable architectural and compositional complexity is challenging. Here we report the synthesis of three types of ternary MOF-on-MOF heterostructures via a multiple selective assembly strategy. This strategy relies on the choice of one host MOF with more than one facet that can arrange the growth of a guest MOF, where the arrangement is site-selective without homogenous growth of guest MOF or homogenous coating of guest on host MOF. The growth of guest MOF on a selected site of host MOF in each step provides the opportunity to further vary the combinations of arrangements in multiple steps, leading to ternary MOF-on-MOF heterostructures with tunable complexity. The developed strategy paves the way towards the rational design of intricate and unprecedented MOF-based superstructures for various applications.
A yolk–shell Sn@C nanobox composite with controllable structures has been synthesized using a facile approach. The void space is engineered to fit the volume expansion of Sn during cycling. It is ...demonstrated that the shell thickness of carbon nanobox has substantial influence on both nanostructures and the electrochemical performance. With an optimized shell thickness, a high reversible capacity of 810 mA h g−1 can be maintained after 500 cycles, corresponding to 90% retention of the second discharge capacity. For Sn@C materials with either thinner or thicker carbon shells, significant capacity decay or a decreased specific capacity are observed during cycling. The present study sheds light on the rational design of nanostructured electrode materials with enhanced electrochemical performance for next‐generation lithium ion batteries.
A novel yolk–shell Sn@C nanobox composite with controllable structures has been synthesized using a facile approach. The generation of metallic Sn together with the void space and the conversion of polymer to carbon are simultaneously completed in one step. Importantly, with an optimized carbon shell thickness, the composite exhibits high specific capacity, good rate performance, and exceptional cycling stability.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Therapeutic proteins are widely used in clinic for numerous therapies such as cancer therapy, immune therapy, diabetes management and infectious diseases control. The low stability and large size of ...proteins generally compromise their therapeutic effects. Thus, it is a big challenge to deliver active forms of proteins into targeted place in a controlled manner. Nanoparticle based delivery systems offer a promising method to address the challenges. In particular, mesoporous silica nanoparticles (MSNs) are of special interest for protein delivery due to their excellent biocompatibility, high stability, rigid framework, well-defined pore structure, easily controllable morphology and tuneable surface chemistry. Therefore, enhanced stability, improved activity, responsive release, and intracellular delivery of proteins have been achieved using MSNs as delivery vehicles. Here, we systematically review the effects of various structural parameters of MSNs on protein loading, protection, and delivery performance. We also highlight the status of the most recent progress using MSNs for intracellular delivery, extracellular delivery, antibacterial proteins delivery, enzyme mobilization, and catalysis.
Silica nanoparticles have entered clinical trials for a variety of biomedical applications, including oral drug delivery, diagnostics, plasmonic resonance and photothermal ablation therapy. ...Preliminary results indicate the safety, efficacy and viability of silica nanoparticles under these clinical scenarios.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
Silica based nanoparticles have emerged as a promising vaccine delivery system for cancer immunotherapy, but their bio-degradability, adjuvanticity and the resultant antitumor activity remain to be ...largely improved. In this study, we report biodegradable glutathione-depletion dendritic mesoporous organosilica nanoparticles (GDMON) with a tetrasulfide-incorporated framework as a novel co-delivery platform in cancer immunotherapy. Functionalized GDMON are capable of co-delivering an antigen protein (ovalbumin) and a toll-like receptor 9 (TLR9) agonist into antigen presenting cells (APCs) and inducing endosome escape. Moreover, decreasing the intracellular glutathione (GSH) level through the -S-S-/GSH redox chemistry increases the ROS generation level both in vitro and in vivo, facilitating cytotoxic T lymphocyte (CTL) proliferation and reducing tumour growth in an aggressive B16-OVA melanoma tumour model. Our results have shown the potential of GDMON as a novel self-adjuvant and co-delivery nanocarrier for cancer vaccine.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Iron oxide nanoparticles (IONPs) have emerging anticancer applications via polarizing tumor-associated macrophages from tumor-promoting phenotype (M2) to tumor-suppressing phenotype (M1). However, ...the underlying mechanism and structure–function relationship remain unclear. We report magnetite IONPs are more effective compared to hematite in M1 polarization and tumor suppression. Moreover, magnetite IONPs specifically rely on interferon regulatory factor 5 signaling pathway for M1 polarization and down-regulate M2-assoicated arginase-1. This study provides new understandings and paves the way for designing advanced iron-based anticancer technologies.
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IJS, KILJ, NUK, PNG, UL, UM
In this paper, a targeted drug delivery system has been developed based on hyaluronic acid (HA) modified mesoporous silica nanoparticles (MSNs). HA-MSNs possess a specific affinity to CD44 ...over-expressed on the surface of a specific cancer cell line, HCT-116 (human colon cancer cells). The cellular uptake performance of fluorescently labelled MSNs with and without HA modification has been evaluated by confocal microscopy and fluorescence-activated cell sorter (FACS) analysis. Compared to bare MSNs, HA-MSNs exhibit a higher cellular uptake
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HA receptor mediated endocytosis. An anticancer drug, doxorubicin hydrochloride (Dox), has been loaded into MSNs and HA-MSNs as drug delivery vehicles. Dox loaded HA-MSNs show greater cytotoxicity to HCT-116 cells than free Dox and Dox-MSNs due to the enhanced cell internalization behavior of HA-MSNs. It is expected that HA-MSNs have a great potential in targeted delivery of anticancer drugs to CD44 over-expressing tumors.
An anticancer drug delivery system based on hyaluronic acid conjugated mesoporous silica nanoparticles has been developed to specifically target CD44 over-expressing cancer cells, showing significantly enhanced cytotoxicity compared with the free drug.
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