The current targeting drug delivery mainly relies on cancer cell surface receptors.However,in many cases,binding affinities between protein receptors and homing ligands is relatively low and the expression level betwe...The current targeting drug delivery mainly relies on cancer cell surface receptors.However,in many cases,binding affinities between protein receptors and homing ligands is relatively low and the expression level between cancer and normal cells is not significant.Distinct from conventional targeting strategies,we have developed a general cancer targeting platform by building artificial receptor on cancer cell surface via a chemical remodeling of cell surface glycans.A new tetrazine(Tz)functionalized chemical receptor has been designed and efficiently installed on cancer cell surface as“overexpressed”biomarker through a metabolic glycan engineering.Different from the reported bioconjugation for drug targeting,the tetrazine labeled cancer cells not only locally activate TCO-caged prodrugs but also release active drugs via the unique bioorthogonal Tz-TCO click-release reaction.The studies have demonstrated that the new drug targeting strategy enables local activation of prodrug,which ultimately leads to effective and safe cancer therapy.展开更多
A copper-based metal-organic framework(MOF)HKUST-1[Cu_(3)(BTC)2](H_(3)BTC=1,3,5-benzenetricarbocylic acid)was utilized as an artificial receptor to recognize a serine protease,α-chymotrypsin(ChT),with high affinity b...A copper-based metal-organic framework(MOF)HKUST-1[Cu_(3)(BTC)2](H_(3)BTC=1,3,5-benzenetricarbocylic acid)was utilized as an artificial receptor to recognize a serine protease,α-chymotrypsin(ChT),with high affinity by both electrostatic interactions and coordination interactions.The buffer molecule 4-(2-hydroxyethyl)-1-piperazinepropanesulfonic acid(HEPPS)could bind with copper(II)centers and form a negatively charged surface,leading to an electrostatic interaction between the cations on the surface of ChT.Meanwhile,according to Hard Soft Acid Base(HSAB)theory,the borderline Lewis acidic copper(II)centers could coordinate with the intermediate basic imidazole of His-57 at the active sites of ChT,preventing the binding of the substrate.Moreover,through coordination control by adding additional modulators,the different exposed facets with different arrangements of metal clusters and organic linkers could be obtained.Because the enzyme has different interactions with the metal centers and the organic linkers,the affinity between HKUST-1 and ChT could be well tuned.When more{111}facets than{100}facets existed in HKUST-1,the material exhibited better inhibition efficiency towards ChT.展开更多
A pair of artificial enantiotopic receptors la and lb composed of (S,S) or (R,R) chiral bicyclic guanidinium, azacrown ether and (t-butyldiphenylsilyloxy) methyl group for amino acid zwitterions have been synthesized....A pair of artificial enantiotopic receptors la and lb composed of (S,S) or (R,R) chiral bicyclic guanidinium, azacrown ether and (t-butyldiphenylsilyloxy) methyl group for amino acid zwitterions have been synthesized. The liquid-liquid competition experiments and 1 H NMR studies indicate that the receptor 1a with (S, S) configuration and 1b with (R,R) configuration selectively recognize L- and D-aromatic amino acids & respectively.展开更多
Concurrent perception of static and dynamic tactile stimuli is essential for natural haptic feedback and precise manipulation.However,most artificial tactile sensors remain limited to either static,dynamic,or temperat...Concurrent perception of static and dynamic tactile stimuli is essential for natural haptic feedback and precise manipulation.However,most artificial tactile sensors remain limited to either static,dynamic,or temperature sensing due to reliance on specific mechanisms for each modality.Integrating these capabilities in a single artificial receptor is still challenging,particularly when spike-based signals are used as the primary encoding strategies.Here,we present an artificial sensory receptor that decodes spike patterns to perceive static,dynamic,and thermal stimuli simultaneously.By applying a pulsed DC bias across a mixed ion-electron conductor,the device continuously produces encoded spike patterns without additional signal conversion circuitry.Furthermore,the engineered combination of stretchable electrodes and the mixed conductor allows decoupling of mechanical and thermal responses,eliminating signal interference.This simple structure enables reliable,real-time recognition of multiple tactile inputs,including pressure,strain,temperature,and vibration,through a single channel.展开更多
基金financial support from NIH 5R01GM130772R.Ken Coit College of PharmacyArizona Center for Drug Discovery at the University of Arizona,USA。
文摘The current targeting drug delivery mainly relies on cancer cell surface receptors.However,in many cases,binding affinities between protein receptors and homing ligands is relatively low and the expression level between cancer and normal cells is not significant.Distinct from conventional targeting strategies,we have developed a general cancer targeting platform by building artificial receptor on cancer cell surface via a chemical remodeling of cell surface glycans.A new tetrazine(Tz)functionalized chemical receptor has been designed and efficiently installed on cancer cell surface as“overexpressed”biomarker through a metabolic glycan engineering.Different from the reported bioconjugation for drug targeting,the tetrazine labeled cancer cells not only locally activate TCO-caged prodrugs but also release active drugs via the unique bioorthogonal Tz-TCO click-release reaction.The studies have demonstrated that the new drug targeting strategy enables local activation of prodrug,which ultimately leads to effective and safe cancer therapy.
基金supported the National Natural Science Foundation of China(NSFC Grant Numbers 21922407)the Young Elite Scholar Support(YESS)Program from CAST,the Program of Jiangsu Specially-Appointed Professor,the NSF of Jiangsu Province of China(No.BK20190086)the Innovation Team Program of Jiangsu Province of China,and the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘A copper-based metal-organic framework(MOF)HKUST-1[Cu_(3)(BTC)2](H_(3)BTC=1,3,5-benzenetricarbocylic acid)was utilized as an artificial receptor to recognize a serine protease,α-chymotrypsin(ChT),with high affinity by both electrostatic interactions and coordination interactions.The buffer molecule 4-(2-hydroxyethyl)-1-piperazinepropanesulfonic acid(HEPPS)could bind with copper(II)centers and form a negatively charged surface,leading to an electrostatic interaction between the cations on the surface of ChT.Meanwhile,according to Hard Soft Acid Base(HSAB)theory,the borderline Lewis acidic copper(II)centers could coordinate with the intermediate basic imidazole of His-57 at the active sites of ChT,preventing the binding of the substrate.Moreover,through coordination control by adding additional modulators,the different exposed facets with different arrangements of metal clusters and organic linkers could be obtained.Because the enzyme has different interactions with the metal centers and the organic linkers,the affinity between HKUST-1 and ChT could be well tuned.When more{111}facets than{100}facets existed in HKUST-1,the material exhibited better inhibition efficiency towards ChT.
文摘A pair of artificial enantiotopic receptors la and lb composed of (S,S) or (R,R) chiral bicyclic guanidinium, azacrown ether and (t-butyldiphenylsilyloxy) methyl group for amino acid zwitterions have been synthesized. The liquid-liquid competition experiments and 1 H NMR studies indicate that the receptor 1a with (S, S) configuration and 1b with (R,R) configuration selectively recognize L- and D-aromatic amino acids & respectively.
基金funded by the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(No.RS-2024-00338686 and No.2410002523)。
文摘Concurrent perception of static and dynamic tactile stimuli is essential for natural haptic feedback and precise manipulation.However,most artificial tactile sensors remain limited to either static,dynamic,or temperature sensing due to reliance on specific mechanisms for each modality.Integrating these capabilities in a single artificial receptor is still challenging,particularly when spike-based signals are used as the primary encoding strategies.Here,we present an artificial sensory receptor that decodes spike patterns to perceive static,dynamic,and thermal stimuli simultaneously.By applying a pulsed DC bias across a mixed ion-electron conductor,the device continuously produces encoded spike patterns without additional signal conversion circuitry.Furthermore,the engineered combination of stretchable electrodes and the mixed conductor allows decoupling of mechanical and thermal responses,eliminating signal interference.This simple structure enables reliable,real-time recognition of multiple tactile inputs,including pressure,strain,temperature,and vibration,through a single channel.
