Sulfur mustard(SM) can be absorbed by skin quickly and cause serious system damage via reacting with nearly all cell constituents. Until now, there is still lack of effective antidotal therapy for SM and skin protecti...Sulfur mustard(SM) can be absorbed by skin quickly and cause serious system damage via reacting with nearly all cell constituents. Until now, there is still lack of effective antidotal therapy for SM and skin protection is highly important to defend SM. In this article, supramolecular liquid barrier based on pillar[5]arene with triethylene oxide substituents(EGP5) has been designed to impede the skin permeation of SM and further interaction with the skin tissue. EGP5 could encapsulate SM within its cavity, with a Kavalue of(5.10 ± 0.47) × 10^(2)L/mol. In vitro skin absorption test proved that EGP5 was capable to effectively prevent SM from penetrating through skin. This supramolecular liquid barrier was employed on rat models to systematically evaluate protective effect against SM intoxication. Pretreatment of EGP5could alleviate skin and system damage induced by SM and improve survival rate of poisoned rat models from 10% to 90%. Additionally, EGP5 served as protective materials could be highly reused after recycling several times. Overall, these findings have provided the first insight into the construction of convenient liquid material for SM protection.展开更多
Neuromuscular blocking agents(NMBAs)are extensively used during anesthesia to improve surgical conditions by relaxing skeletal muscle movements.Rapid neuromuscular recovery after surgery is desirable to facilitate the...Neuromuscular blocking agents(NMBAs)are extensively used during anesthesia to improve surgical conditions by relaxing skeletal muscle movements.Rapid neuromuscular recovery after surgery is desirable to facilitate the recovery of muscle function and prevent residual blockade.Decamethonium(C10)is a classic NMBA,which has been restricted over the past decades ascribed to lack of a suitable antidote in clinic.Herein we used carboxylatopillar[6]arene(CP6A)to reverse neuromuscular blocker effect of C10 through direct host-vip encapsulation.NMR and isothermal titration calorimetry served to confirm the complexation between CP6A and C10 with robust affinity[(1.07±0.14)×10^(7)L/mol].The CP6A was further used as a reversal agent of C10,which facilitated to decrease C10 concentration in mice blood and excrete via urinary clearance,resulting in rapid recovery from muscle relaxation.These favorable outcomes might lead us to suggest that this supramolecular strategy could allow patients to regain lucidity much faster than spontaneous recovery from anesthesia.展开更多
Advanced chemotherapy strategies are in urgent demand for improving anticancer efficacy.Herein,a water-soluble pillar[6]arene(WP6 A)was used to load chemotherapeutic agent pemetrexed(PMX)by forming direct host-vip i...Advanced chemotherapy strategies are in urgent demand for improving anticancer efficacy.Herein,a water-soluble pillar[6]arene(WP6 A)was used to load chemotherapeutic agent pemetrexed(PMX)by forming direct host-vip inclusion,which is beneficial for decreasing cytotoxicity of PMX on BEAS-2 B cells.NMR and florescence titration served to confirm the complexation between WP6 A and ATP with higher affinity[(5.67?0.31)x 10^(5)L/mol],favoring competitive replacement of PMX.Complexation ATP by WP6 A effectively prevented ATP from being hydrolyzed in presence of alkaline phosphatase.The formed host-vip complex was further used to block the efflux pump by cutting off energy source from ATP hydrolysis,which was accompanied with releasing PMX to produce synergistic enhancement of anticancer performance towards A549 cells.This supramolecular strategy would also be extended to other clinical chemotherapeutic agents and it was expected to provide salutary profits for cancer patients.展开更多
Fentanyl(Fen)analogs,clinically used anesthetic adjuvants,are often trouble with overdose‐induced adverse effects due torapid entry into the brain plus short retention time.Advanced approaches that can relieve relate...Fentanyl(Fen)analogs,clinically used anesthetic adjuvants,are often trouble with overdose‐induced adverse effects due torapid entry into the brain plus short retention time.Advanced approaches that can relieve related life‐threatening symptomswithout compromising their anesthetic efficacy are urgently needed to satisfy these special requirements.Herein,we proposethat utilization of a well‐matched macrocycle,terphen[3]arene sulfate(TP3S)as a molecular‐level brake for Fen via thepharmacokinetic mode to execute this task.NMR and titration experiments confirm that TP3S possessed strong complexationability toward Fen with an association constant of(1.36±0.12)×10^(6)M^(−1).Then,Transwell assays demonstrate that TP3S itselfis unable to cross the blood–brain barrier,and codosed with Fen could effectively decelerate its velocity of entering the brain.Respiration‐related evaluations and pharmacodynamics analyses reveal that administration of such a brake alleviatesFen‐induced respiratory depression without losing its effectiveness.The therapeutic index of Fen/TP3S is calculated to be~57%higher than that of Fen alone,and through pharmacokinetic studies,it has been clarified that ameliorating Fen's therapeuticoutcome stemmed from reducing the initial brain concentration of Fen and maintaining its effective dose for a longer time.Thissupramolecular approach could also act on other opioids as long as strong binding was achieved.展开更多
基金financially supported by National Natural Science Foundation of China (Nos. 22171286, 21772118, 21971192)the Natural Science Foundation of Tianjin City (No. 20JCZDJC00200)the Special Fund of Military Medical Science (Nos. BWS16J007,AWS17J009)。
文摘Sulfur mustard(SM) can be absorbed by skin quickly and cause serious system damage via reacting with nearly all cell constituents. Until now, there is still lack of effective antidotal therapy for SM and skin protection is highly important to defend SM. In this article, supramolecular liquid barrier based on pillar[5]arene with triethylene oxide substituents(EGP5) has been designed to impede the skin permeation of SM and further interaction with the skin tissue. EGP5 could encapsulate SM within its cavity, with a Kavalue of(5.10 ± 0.47) × 10^(2)L/mol. In vitro skin absorption test proved that EGP5 was capable to effectively prevent SM from penetrating through skin. This supramolecular liquid barrier was employed on rat models to systematically evaluate protective effect against SM intoxication. Pretreatment of EGP5could alleviate skin and system damage induced by SM and improve survival rate of poisoned rat models from 10% to 90%. Additionally, EGP5 served as protective materials could be highly reused after recycling several times. Overall, these findings have provided the first insight into the construction of convenient liquid material for SM protection.
基金the Natural Science Foundation of Beijing Municipality(No.7204285)the National Natural Science Foundation of China(Nos.81573354,21772118,21971192)。
文摘Neuromuscular blocking agents(NMBAs)are extensively used during anesthesia to improve surgical conditions by relaxing skeletal muscle movements.Rapid neuromuscular recovery after surgery is desirable to facilitate the recovery of muscle function and prevent residual blockade.Decamethonium(C10)is a classic NMBA,which has been restricted over the past decades ascribed to lack of a suitable antidote in clinic.Herein we used carboxylatopillar[6]arene(CP6A)to reverse neuromuscular blocker effect of C10 through direct host-vip encapsulation.NMR and isothermal titration calorimetry served to confirm the complexation between CP6A and C10 with robust affinity[(1.07±0.14)×10^(7)L/mol].The CP6A was further used as a reversal agent of C10,which facilitated to decrease C10 concentration in mice blood and excrete via urinary clearance,resulting in rapid recovery from muscle relaxation.These favorable outcomes might lead us to suggest that this supramolecular strategy could allow patients to regain lucidity much faster than spontaneous recovery from anesthesia.
基金the National Natural Science Foundation of China(Nos.21772118,21971192,81573354)the Natural Science Foundation of Tianjin City(No.20JCZDJC00200)。
文摘Advanced chemotherapy strategies are in urgent demand for improving anticancer efficacy.Herein,a water-soluble pillar[6]arene(WP6 A)was used to load chemotherapeutic agent pemetrexed(PMX)by forming direct host-vip inclusion,which is beneficial for decreasing cytotoxicity of PMX on BEAS-2 B cells.NMR and florescence titration served to confirm the complexation between WP6 A and ATP with higher affinity[(5.67?0.31)x 10^(5)L/mol],favoring competitive replacement of PMX.Complexation ATP by WP6 A effectively prevented ATP from being hydrolyzed in presence of alkaline phosphatase.The formed host-vip complex was further used to block the efflux pump by cutting off energy source from ATP hydrolysis,which was accompanied with releasing PMX to produce synergistic enhancement of anticancer performance towards A549 cells.This supramolecular strategy would also be extended to other clinical chemotherapeutic agents and it was expected to provide salutary profits for cancer patients.
基金supported by the National Natural Science Foundation of China(22171286 and 22201212).
文摘Fentanyl(Fen)analogs,clinically used anesthetic adjuvants,are often trouble with overdose‐induced adverse effects due torapid entry into the brain plus short retention time.Advanced approaches that can relieve related life‐threatening symptomswithout compromising their anesthetic efficacy are urgently needed to satisfy these special requirements.Herein,we proposethat utilization of a well‐matched macrocycle,terphen[3]arene sulfate(TP3S)as a molecular‐level brake for Fen via thepharmacokinetic mode to execute this task.NMR and titration experiments confirm that TP3S possessed strong complexationability toward Fen with an association constant of(1.36±0.12)×10^(6)M^(−1).Then,Transwell assays demonstrate that TP3S itselfis unable to cross the blood–brain barrier,and codosed with Fen could effectively decelerate its velocity of entering the brain.Respiration‐related evaluations and pharmacodynamics analyses reveal that administration of such a brake alleviatesFen‐induced respiratory depression without losing its effectiveness.The therapeutic index of Fen/TP3S is calculated to be~57%higher than that of Fen alone,and through pharmacokinetic studies,it has been clarified that ameliorating Fen's therapeuticoutcome stemmed from reducing the initial brain concentration of Fen and maintaining its effective dose for a longer time.Thissupramolecular approach could also act on other opioids as long as strong binding was achieved.
