Hitchhiking bioorthogonal nanozymes on red blood cells for selective killing of pathogenic bacter... more Hitchhiking bioorthogonal nanozymes on red blood cells for selective killing of pathogenic bacterial infections.
The emergence of multidrug‐resistant (MDR) pathogenic bacteria constitutes a key threat to global... more The emergence of multidrug‐resistant (MDR) pathogenic bacteria constitutes a key threat to global health. Infections caused by multidrug‐resistant Gram‐negative bacteria are particularly challenging to treat due to the ability of pathogens to prevent antibiotic penetration inside the bacterial membrane. Antibiotic therapy is further rendered ineffective due to biofilm formation where the protective extracellular polymeric substance matrix limits the diffusion of antibiotics inside the biofilm. It is hypothesized that careful engineering of chemical groups on polymer scaffolds can enable polymers to penetrate the barriers of Gram‐negative bacterial membrane and biofilm matrix. Here, the use of engineered polymeric nanoparticles in combination with antibiotics for synergistic antimicrobial therapy is presented. These polymeric nanoparticles enhance the accumulation of antibiotics inside Gram‐negative bacteria and the biofilm matrix, resulting in increased potency of antibiotics in combination therapy. Sublethal concentrations of engineered polymeric nanoparticles reduce the antibiotic dosage by 32‐fold to treat MDR bacteria and biofilms. Tailoring of chemical groups on polymers demonstrates a strong structure–activity relationship in generating additive and synergistic combinations with antibiotics. This study demonstrates the ability of polymeric nanoparticles to “rejuvenate” antibiotics rendered ineffective by resistant bacteria and provides a rationale to design novel compounds to achieve effective antimicrobial combination therapies.
Macrophages are key effectors of host defense and metabolism, making them promising targets for t... more Macrophages are key effectors of host defense and metabolism, making them promising targets for transient genetic therapy. Gene editing through the delivery of Cas9-ribonucleoprotein (RNP) provides multiple advantages over gene delivery-based strategies for introducing CRISPR machinery to the cell. There are, however, significant physiological, cellular, and intracellular barriers to the effective delivery of the Cas9 protein and guide RNA (sgRNA) that have to date, restricted in vivo Cas9 protein-based approaches to local/topical delivery applications. Described herein is a new nanoassembled platform featuring coengineered nanoparticles and Cas9 protein that has been developed to provide efficient Cas9-sgRNA delivery and concomitant CRISPR editing through systemic tail-vein injection into mice, achieving >8% gene editing efficiency in macrophages of the liver and spleen.
We report a modular strategy for the solubilization and protection of hydrophobic transition meta... more We report a modular strategy for the solubilization and protection of hydrophobic transition metal catalysts using the hydrophobic pockets of water soluble gold nanoparticles. Beside preserving original catalyst activity, this encapsulation strategy provides a protective environment for the hydrophobic catalyst and brings reusability. This system provides a versatile platform for the encapsulation of different hydrophobic transition metal catalysts, allowing a wide range of catalysis in water while uniting the advantages of homogeneous and heterogeneous catalysis in the same system.
Bioorthogonal transformation of prodrugs and profluorophores using transition metal catalysts (TM... more Bioorthogonal transformation of prodrugs and profluorophores using transition metal catalysts (TMC) offers a promising strategy for therapeutic and imaging applications. Here, we report the surface engineering of nanoparticles to specifically localize gold nanoparticles (AuNPs) with encapsulated TMCs
Bacterial multidrug resistance (MDR) is a serious healthcare issue caused by the long-term subthe... more Bacterial multidrug resistance (MDR) is a serious healthcare issue caused by the long-term subtherapeutic clinical treatment of infectious diseases. Nanoscale engineering of metal nanoparticles has great potential to address this issue by tuning the nano−bio interface to target bacteria. Herein, we report the use of branched polyethylenimine-functionalized silver nanoclusters (bPEI−Ag NCs) to selectively kill MDR pathogenic bacteria by combining the antimicrobial activity of silver with the selective toxicity of bPEI toward bacteria. The minimum inhibitory concentration of bPEI−Ag NCs was determined against 12 uropathogenic MDR strains and found to be 10-to 15-fold lower than that of PEI and 2-to 3-fold lower than that of AgNO 3 alone. Cell viability and hemolysis assays demonstrated the biocompatibility of bPEI−Ag NCs with human fibroblasts and red blood cells, with selective toxicity against MDR bacteria.
Journal of controlled release : official journal of the Controlled Release Society, Jan 10, 2018
The use of nanoparticle-stabilized nanocapsules for cytosolic siRNA delivery for immunomodulation... more The use of nanoparticle-stabilized nanocapsules for cytosolic siRNA delivery for immunomodulation in vitro and in vivo is reported. These NPSCs deliver siRNA directly to the cytosol of macrophages in vitro with concomitant knockdown of gene expression. In vivo studies showed directed delivery of NPSCs to the spleen, enabling gene silencing of macrophages, with preliminary studies showing 70% gene knockdown at a siRNA dose of 0.28 mg/kg. Significantly, the delivery of siRNA targeting tumor necrosis factor-α efficiently silenced TNF-α expression in LPS-challenged mice, demonstrating efficacy in modulating immune response in an organ-selective manner. This research highlights the potential of the NPSC platform for targeted immunotherapy and further manipulation of the immune system.
Journal of the American Chemical Society, Jan 31, 2018
The rapid emergence of antibiotic-resistant bacterial "superbugs" with concomitant trea... more The rapid emergence of antibiotic-resistant bacterial "superbugs" with concomitant treatment failure and high mortality rates presents a severe threat to global health. The superbug risk is further exacerbated by chronic infections generated from antibiotic-resistant biofilms that render them refractory to available treatments. We hypothesized that efficient antimicrobial agents could be generated through careful engineering of hydrophobic and cationic domains in a synthetic semi-rigid polymer scaffold, mirroring and amplifying attributes of antimicrobial peptides. We report the creation of poly-meric nanoparticles with highly efficient antimicrobial properties. These nanoparticles eradicate biofilms with low toxicity to mammalian cells and feature unprecedented therapeutic indices against red blood cells. Most notably, bacterial re-sistance towards these nanoparticles was not observed after 20 serial passages, in stark contrast to clinically relevant anti-biotics where si...
Early detection of biofilms is crucial for limiting infection-based damage. Imaging these biofilm... more Early detection of biofilms is crucial for limiting infection-based damage. Imaging these biofilms is challenging: conventional imaging agents are unable to penetrate the dense matrix of the biofilm, and many imaging agents are susceptible to false positive/negative responses due to phenotypical mutations of the constituent microbes. We report the creation of pH-responsive nanoparticles with embedded transition metal catalysts (nanozymes) that effectively target the acidic microenvironment of biofilms. These pH-switchable nanozymes generate imaging agents through bioorthogonal activation of profluorophores inside biofilms. The specificity of these nanozymes for imaging biofilms in complex biosystems was demonstrated using coculture experiments.
Infections caused by multidrug-resistant (MDR) bacteria pose a serious global burden of mortality... more Infections caused by multidrug-resistant (MDR) bacteria pose a serious global burden of mortality, causing thousands of deaths each year. Antibiotic treatment of resistant infections further contributes to the rapidly increasing number of antibiotic-resistant species and strains. Synthetic macromolecules such as nanoparticles (NPs) exhibit broad-spectrum activity against MDR species, however lack of specificity towards bacteria relative to their mammalian hosts limits their widespread therapeutic application. Here, we demonstrate synergistic antimicrobial therapy using hydrophobically functionalized NPs and fluoroquinolone antibiotics for treatment of MDR bacterial strains. An 8-16-fold decrease in antibiotic dosage is achieved in presence of engineered NPs to combat MDR strains. This strategy demonstrates the potential of using NPs to 'revive' antibiotics that have been rendered ineffective due to the development of resistance by pathogenic bacteria.
Infections caused by bacterial biofilms are an emerging threat to human health. Conventional anti... more Infections caused by bacterial biofilms are an emerging threat to human health. Conventional antibiotic therapies are ineffective against biofilms due to poor penetration of the extracellular polymeric substance secreted by colonized bacteria coupled with the rapidly growing number of antibiotic-resistant strains. Essential oils are promising natural antimicrobial agents; however, poor solubility in biological conditions limits their applications against bacteria in both dispersed (planktonic) and biofilm settings. We report here an oil-in-water cross-linked polymeric nanocomposite (∼250 nm) incorporating carvacrol oil that penetrates and eradicates multidrug-resistant (MDR) biofilms. The therapeutic potential of these materials against challenging wound biofilm infections was demonstrated through specific killing of bacteria in a mammalian cell-biofilm coculture wound model.
Gold nanoparticles provide an excellent platform for biological and material applications due to ... more Gold nanoparticles provide an excellent platform for biological and material applications due to their unique physical and chemical properties. However, decreased colloidal stability and formation of irreversible aggregates while freeze-drying nanomaterials, limits their use in real world applications. Here, we report a new generation of surface ligands based on a combination of short oligo (ethylene glycol) chain and zwitterions capable of providing non-fouling characteristics, while maintaining colloidal stability and functionalization capabilities. Additionally, conjugation of these gold nanoparticles with avidin can help developing a universal toolkit for further functionalization of nanomaterials.
This paper rationalizes the green and scalable synthesis of graphenic materials of different aspe... more This paper rationalizes the green and scalable synthesis of graphenic materials of different aspect ratios using anthracite coal as a single source material under different supercritical solvents. Single layer, monodisperse graphene oxide quantum dots (GQDs) are obtained at high yield (55wt%) from anthracite coal in supercritical water. The obtained GQDs are ~3 nm in lateral size and display a high fluorescence quantum yield of 28%. They show high cell viability and are readily used for imaging cancer cells. In an analogous experiment, high aspect ratio graphenic materials with ribbon like morphology (GRs) are synthesized from the same source material in supercritical ethanol at a yield of 6.4wt%. A thin film of GRs with 68% transparency shows a surface resistance of 9.3 kΩ/sq. This is a first demonstration of anthracite coal as a source for electrically conductive graphenic materials.
Using a family of cationic gold nanoparticles (NPs) with similar size and charge, we demonstrate ... more Using a family of cationic gold nanoparticles (NPs) with similar size and charge, we demonstrate that proper surface engineering can control the nature and identity of protein corona in physiological serum conditions. The protein coronas were highly dependent on the hydrophobicity and arrangement of chemical motifs on NP surface. The NPs were uptaken in macrophages in a corona-dependent manner, predominantly through recognition of specific complement proteins in the NP corona. Taken together, this study shows that surface functionality can be used to tune the protein corona formed on NP surface, dictating the interaction of NPs with macrophages.
Correlation of the surface physicochemical properties of nanoparticles with their interactions wi... more Correlation of the surface physicochemical properties of nanoparticles with their interactions with biosystems provides key foundational data for nanomedicine. We report here the systematic synthesis of 2, 4, and 6 nm core gold nanoparticles (AuNP) featuring neutral (zwitterionic), anionic, and cationic headgroups. The cellular internalization of these AuNPs was quantified, providing a parametric evaluation of charge and size effects. Contrasting behavior was observed with these systems: with zwitterionic and anionic particles, uptake decreased with increasing AuNP size, whereas with cationic particles uptake increased with increasing particle size. Through mechanistic studies of the uptake process we can attribute these opposing trends to a surface-dictated shift in uptake pathways. Zwitterionic NPs are primarily internalized through passive diffusion, while the internalization of cationic and anionic NPs is dominated by multiple endocytic pathways. Our study demonstrates that size...
Bioorthogonal catalysis broadens the functional possibilities of intracellular chemistry. Effecti... more Bioorthogonal catalysis broadens the functional possibilities of intracellular chemistry. Effective delivery and regulation of synthetic catalytic systems in cells are challenging due to the complex intracellular environment and catalyst instability. Here, we report the fabrication of protein-sized bioorthogonal nanozymes through the encapsulation of hydrophobic transition metal catalysts into the monolayer of water-soluble gold nanoparticles. The activity of these catalysts can be reversibly controlled by binding a supramolecular cucurbit[7]uril 'gate-keeper' onto the monolayer surface, providing a biomimetic control mechanism that mimics the allosteric regulation of enzymes. The potential of this gated nanozyme for use in imaging and therapeutic applications was demonstrated through triggered cleavage of allylcarbamates for pro-fluorophore activation and propargyl groups for prodrug activation inside living cells.
Host-guest interactions between a synthetic receptor, cucurbit[7]uril (CB[7]), and gold nanoparti... more Host-guest interactions between a synthetic receptor, cucurbit[7]uril (CB[7]), and gold nanoparticles (AuNPs) have been quantified using isothermal titration calorimetry. AuNPs were functionalized with ligands containing tertiary or quaternary benzylamine derivatives, with electron donating or withdrawing groups at the para position of the benzene ring. Analysis of binding interactions reveals that functional groups at the para position have no significant effect on binding constant. However, headgroups bearing a permanent positive charge increased the binding of AuNPs to CB[7] tenfold compared to monomethyl counterparts.
Bioorthogonal catalysis broadens the functional possibilities of intracellular chemistry. Effecti... more Bioorthogonal catalysis broadens the functional possibilities of intracellular chemistry. Effective delivery and regulation of synthetic catalytic systems in cells are challenging due to the complex intracellular environment and catalyst instability. Here, we report the fabrication of protein-sized bioorthogonal nanozymes through the encapsulation of hydrophobic transition metal catalysts into the monolayer of water-soluble gold nanoparticles. The activity of these catalysts can be reversibly controlled by binding a supramolecular cucurbit[7]uril 'gate-keeper' onto the monolayer surface, providing a biomimetic control mechanism that mimics the allosteric regulation of enzymes. The potential of this gated nanozyme for use in imaging and therapeutic applications was demonstrated through triggered cleavage of allylcarbamates for pro-fluorophore activation and propargyl groups for prodrug activation inside living cells.
Hitchhiking bioorthogonal nanozymes on red blood cells for selective killing of pathogenic bacter... more Hitchhiking bioorthogonal nanozymes on red blood cells for selective killing of pathogenic bacterial infections.
The emergence of multidrug‐resistant (MDR) pathogenic bacteria constitutes a key threat to global... more The emergence of multidrug‐resistant (MDR) pathogenic bacteria constitutes a key threat to global health. Infections caused by multidrug‐resistant Gram‐negative bacteria are particularly challenging to treat due to the ability of pathogens to prevent antibiotic penetration inside the bacterial membrane. Antibiotic therapy is further rendered ineffective due to biofilm formation where the protective extracellular polymeric substance matrix limits the diffusion of antibiotics inside the biofilm. It is hypothesized that careful engineering of chemical groups on polymer scaffolds can enable polymers to penetrate the barriers of Gram‐negative bacterial membrane and biofilm matrix. Here, the use of engineered polymeric nanoparticles in combination with antibiotics for synergistic antimicrobial therapy is presented. These polymeric nanoparticles enhance the accumulation of antibiotics inside Gram‐negative bacteria and the biofilm matrix, resulting in increased potency of antibiotics in combination therapy. Sublethal concentrations of engineered polymeric nanoparticles reduce the antibiotic dosage by 32‐fold to treat MDR bacteria and biofilms. Tailoring of chemical groups on polymers demonstrates a strong structure–activity relationship in generating additive and synergistic combinations with antibiotics. This study demonstrates the ability of polymeric nanoparticles to “rejuvenate” antibiotics rendered ineffective by resistant bacteria and provides a rationale to design novel compounds to achieve effective antimicrobial combination therapies.
Macrophages are key effectors of host defense and metabolism, making them promising targets for t... more Macrophages are key effectors of host defense and metabolism, making them promising targets for transient genetic therapy. Gene editing through the delivery of Cas9-ribonucleoprotein (RNP) provides multiple advantages over gene delivery-based strategies for introducing CRISPR machinery to the cell. There are, however, significant physiological, cellular, and intracellular barriers to the effective delivery of the Cas9 protein and guide RNA (sgRNA) that have to date, restricted in vivo Cas9 protein-based approaches to local/topical delivery applications. Described herein is a new nanoassembled platform featuring coengineered nanoparticles and Cas9 protein that has been developed to provide efficient Cas9-sgRNA delivery and concomitant CRISPR editing through systemic tail-vein injection into mice, achieving >8% gene editing efficiency in macrophages of the liver and spleen.
We report a modular strategy for the solubilization and protection of hydrophobic transition meta... more We report a modular strategy for the solubilization and protection of hydrophobic transition metal catalysts using the hydrophobic pockets of water soluble gold nanoparticles. Beside preserving original catalyst activity, this encapsulation strategy provides a protective environment for the hydrophobic catalyst and brings reusability. This system provides a versatile platform for the encapsulation of different hydrophobic transition metal catalysts, allowing a wide range of catalysis in water while uniting the advantages of homogeneous and heterogeneous catalysis in the same system.
Bioorthogonal transformation of prodrugs and profluorophores using transition metal catalysts (TM... more Bioorthogonal transformation of prodrugs and profluorophores using transition metal catalysts (TMC) offers a promising strategy for therapeutic and imaging applications. Here, we report the surface engineering of nanoparticles to specifically localize gold nanoparticles (AuNPs) with encapsulated TMCs
Bacterial multidrug resistance (MDR) is a serious healthcare issue caused by the long-term subthe... more Bacterial multidrug resistance (MDR) is a serious healthcare issue caused by the long-term subtherapeutic clinical treatment of infectious diseases. Nanoscale engineering of metal nanoparticles has great potential to address this issue by tuning the nano−bio interface to target bacteria. Herein, we report the use of branched polyethylenimine-functionalized silver nanoclusters (bPEI−Ag NCs) to selectively kill MDR pathogenic bacteria by combining the antimicrobial activity of silver with the selective toxicity of bPEI toward bacteria. The minimum inhibitory concentration of bPEI−Ag NCs was determined against 12 uropathogenic MDR strains and found to be 10-to 15-fold lower than that of PEI and 2-to 3-fold lower than that of AgNO 3 alone. Cell viability and hemolysis assays demonstrated the biocompatibility of bPEI−Ag NCs with human fibroblasts and red blood cells, with selective toxicity against MDR bacteria.
Journal of controlled release : official journal of the Controlled Release Society, Jan 10, 2018
The use of nanoparticle-stabilized nanocapsules for cytosolic siRNA delivery for immunomodulation... more The use of nanoparticle-stabilized nanocapsules for cytosolic siRNA delivery for immunomodulation in vitro and in vivo is reported. These NPSCs deliver siRNA directly to the cytosol of macrophages in vitro with concomitant knockdown of gene expression. In vivo studies showed directed delivery of NPSCs to the spleen, enabling gene silencing of macrophages, with preliminary studies showing 70% gene knockdown at a siRNA dose of 0.28 mg/kg. Significantly, the delivery of siRNA targeting tumor necrosis factor-α efficiently silenced TNF-α expression in LPS-challenged mice, demonstrating efficacy in modulating immune response in an organ-selective manner. This research highlights the potential of the NPSC platform for targeted immunotherapy and further manipulation of the immune system.
Journal of the American Chemical Society, Jan 31, 2018
The rapid emergence of antibiotic-resistant bacterial "superbugs" with concomitant trea... more The rapid emergence of antibiotic-resistant bacterial "superbugs" with concomitant treatment failure and high mortality rates presents a severe threat to global health. The superbug risk is further exacerbated by chronic infections generated from antibiotic-resistant biofilms that render them refractory to available treatments. We hypothesized that efficient antimicrobial agents could be generated through careful engineering of hydrophobic and cationic domains in a synthetic semi-rigid polymer scaffold, mirroring and amplifying attributes of antimicrobial peptides. We report the creation of poly-meric nanoparticles with highly efficient antimicrobial properties. These nanoparticles eradicate biofilms with low toxicity to mammalian cells and feature unprecedented therapeutic indices against red blood cells. Most notably, bacterial re-sistance towards these nanoparticles was not observed after 20 serial passages, in stark contrast to clinically relevant anti-biotics where si...
Early detection of biofilms is crucial for limiting infection-based damage. Imaging these biofilm... more Early detection of biofilms is crucial for limiting infection-based damage. Imaging these biofilms is challenging: conventional imaging agents are unable to penetrate the dense matrix of the biofilm, and many imaging agents are susceptible to false positive/negative responses due to phenotypical mutations of the constituent microbes. We report the creation of pH-responsive nanoparticles with embedded transition metal catalysts (nanozymes) that effectively target the acidic microenvironment of biofilms. These pH-switchable nanozymes generate imaging agents through bioorthogonal activation of profluorophores inside biofilms. The specificity of these nanozymes for imaging biofilms in complex biosystems was demonstrated using coculture experiments.
Infections caused by multidrug-resistant (MDR) bacteria pose a serious global burden of mortality... more Infections caused by multidrug-resistant (MDR) bacteria pose a serious global burden of mortality, causing thousands of deaths each year. Antibiotic treatment of resistant infections further contributes to the rapidly increasing number of antibiotic-resistant species and strains. Synthetic macromolecules such as nanoparticles (NPs) exhibit broad-spectrum activity against MDR species, however lack of specificity towards bacteria relative to their mammalian hosts limits their widespread therapeutic application. Here, we demonstrate synergistic antimicrobial therapy using hydrophobically functionalized NPs and fluoroquinolone antibiotics for treatment of MDR bacterial strains. An 8-16-fold decrease in antibiotic dosage is achieved in presence of engineered NPs to combat MDR strains. This strategy demonstrates the potential of using NPs to 'revive' antibiotics that have been rendered ineffective due to the development of resistance by pathogenic bacteria.
Infections caused by bacterial biofilms are an emerging threat to human health. Conventional anti... more Infections caused by bacterial biofilms are an emerging threat to human health. Conventional antibiotic therapies are ineffective against biofilms due to poor penetration of the extracellular polymeric substance secreted by colonized bacteria coupled with the rapidly growing number of antibiotic-resistant strains. Essential oils are promising natural antimicrobial agents; however, poor solubility in biological conditions limits their applications against bacteria in both dispersed (planktonic) and biofilm settings. We report here an oil-in-water cross-linked polymeric nanocomposite (∼250 nm) incorporating carvacrol oil that penetrates and eradicates multidrug-resistant (MDR) biofilms. The therapeutic potential of these materials against challenging wound biofilm infections was demonstrated through specific killing of bacteria in a mammalian cell-biofilm coculture wound model.
Gold nanoparticles provide an excellent platform for biological and material applications due to ... more Gold nanoparticles provide an excellent platform for biological and material applications due to their unique physical and chemical properties. However, decreased colloidal stability and formation of irreversible aggregates while freeze-drying nanomaterials, limits their use in real world applications. Here, we report a new generation of surface ligands based on a combination of short oligo (ethylene glycol) chain and zwitterions capable of providing non-fouling characteristics, while maintaining colloidal stability and functionalization capabilities. Additionally, conjugation of these gold nanoparticles with avidin can help developing a universal toolkit for further functionalization of nanomaterials.
This paper rationalizes the green and scalable synthesis of graphenic materials of different aspe... more This paper rationalizes the green and scalable synthesis of graphenic materials of different aspect ratios using anthracite coal as a single source material under different supercritical solvents. Single layer, monodisperse graphene oxide quantum dots (GQDs) are obtained at high yield (55wt%) from anthracite coal in supercritical water. The obtained GQDs are ~3 nm in lateral size and display a high fluorescence quantum yield of 28%. They show high cell viability and are readily used for imaging cancer cells. In an analogous experiment, high aspect ratio graphenic materials with ribbon like morphology (GRs) are synthesized from the same source material in supercritical ethanol at a yield of 6.4wt%. A thin film of GRs with 68% transparency shows a surface resistance of 9.3 kΩ/sq. This is a first demonstration of anthracite coal as a source for electrically conductive graphenic materials.
Using a family of cationic gold nanoparticles (NPs) with similar size and charge, we demonstrate ... more Using a family of cationic gold nanoparticles (NPs) with similar size and charge, we demonstrate that proper surface engineering can control the nature and identity of protein corona in physiological serum conditions. The protein coronas were highly dependent on the hydrophobicity and arrangement of chemical motifs on NP surface. The NPs were uptaken in macrophages in a corona-dependent manner, predominantly through recognition of specific complement proteins in the NP corona. Taken together, this study shows that surface functionality can be used to tune the protein corona formed on NP surface, dictating the interaction of NPs with macrophages.
Correlation of the surface physicochemical properties of nanoparticles with their interactions wi... more Correlation of the surface physicochemical properties of nanoparticles with their interactions with biosystems provides key foundational data for nanomedicine. We report here the systematic synthesis of 2, 4, and 6 nm core gold nanoparticles (AuNP) featuring neutral (zwitterionic), anionic, and cationic headgroups. The cellular internalization of these AuNPs was quantified, providing a parametric evaluation of charge and size effects. Contrasting behavior was observed with these systems: with zwitterionic and anionic particles, uptake decreased with increasing AuNP size, whereas with cationic particles uptake increased with increasing particle size. Through mechanistic studies of the uptake process we can attribute these opposing trends to a surface-dictated shift in uptake pathways. Zwitterionic NPs are primarily internalized through passive diffusion, while the internalization of cationic and anionic NPs is dominated by multiple endocytic pathways. Our study demonstrates that size...
Bioorthogonal catalysis broadens the functional possibilities of intracellular chemistry. Effecti... more Bioorthogonal catalysis broadens the functional possibilities of intracellular chemistry. Effective delivery and regulation of synthetic catalytic systems in cells are challenging due to the complex intracellular environment and catalyst instability. Here, we report the fabrication of protein-sized bioorthogonal nanozymes through the encapsulation of hydrophobic transition metal catalysts into the monolayer of water-soluble gold nanoparticles. The activity of these catalysts can be reversibly controlled by binding a supramolecular cucurbit[7]uril 'gate-keeper' onto the monolayer surface, providing a biomimetic control mechanism that mimics the allosteric regulation of enzymes. The potential of this gated nanozyme for use in imaging and therapeutic applications was demonstrated through triggered cleavage of allylcarbamates for pro-fluorophore activation and propargyl groups for prodrug activation inside living cells.
Host-guest interactions between a synthetic receptor, cucurbit[7]uril (CB[7]), and gold nanoparti... more Host-guest interactions between a synthetic receptor, cucurbit[7]uril (CB[7]), and gold nanoparticles (AuNPs) have been quantified using isothermal titration calorimetry. AuNPs were functionalized with ligands containing tertiary or quaternary benzylamine derivatives, with electron donating or withdrawing groups at the para position of the benzene ring. Analysis of binding interactions reveals that functional groups at the para position have no significant effect on binding constant. However, headgroups bearing a permanent positive charge increased the binding of AuNPs to CB[7] tenfold compared to monomethyl counterparts.
Bioorthogonal catalysis broadens the functional possibilities of intracellular chemistry. Effecti... more Bioorthogonal catalysis broadens the functional possibilities of intracellular chemistry. Effective delivery and regulation of synthetic catalytic systems in cells are challenging due to the complex intracellular environment and catalyst instability. Here, we report the fabrication of protein-sized bioorthogonal nanozymes through the encapsulation of hydrophobic transition metal catalysts into the monolayer of water-soluble gold nanoparticles. The activity of these catalysts can be reversibly controlled by binding a supramolecular cucurbit[7]uril 'gate-keeper' onto the monolayer surface, providing a biomimetic control mechanism that mimics the allosteric regulation of enzymes. The potential of this gated nanozyme for use in imaging and therapeutic applications was demonstrated through triggered cleavage of allylcarbamates for pro-fluorophore activation and propargyl groups for prodrug activation inside living cells.
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Papers by Riddha Das