The efficacious delivery of antimicrobial drugs to intractable oral biofilms remains a challenge due to inadequate biofilm penetration and lack of pathogen targeting.Herein,we have developed a microenvironment-activat...The efficacious delivery of antimicrobial drugs to intractable oral biofilms remains a challenge due to inadequate biofilm penetration and lack of pathogen targeting.Herein,we have developed a microenvironment-activated poly(ethylene glycol)(PEG)-sheddable nanoplatform to mediate targeted delivery of drugs into oral biofilms for the efficient prevention of dental caries.The PEGylated nanoplatform with enhanced biofilm penetration is capable of deshielding the PEG layer under slightly acidic conditions in a PEG chain length-dependent manner to re-expose the bacteria-targeting ligands,thereby facilitating targeted codelivery of ciprofloxacin(CIP)and IR780 to the bacteria after accumulation within biofilms.The nanoplatform tends to induce bacterial agglomeration and suffers from degradation in the acidic oral biofilm microenvironment,triggering rapid drug release on demand around bacterial cells.The self-modulating nanoplatform under near-infrared(NIR)irradiation accordingly displays greatly augmented potency in oral biofilm penetration and disruption compared with drugs alone.Topical oral treatment with nanoplatforms involving synergetic pharmacological and photothermal/photodynamic trinary therapy results in robust biofilm dispersion and efficacious suppression of severe tooth decay in rats.This versatile nanoplatform can promote local accumulation and specific drug transport into biofilms and represents a new paradigm for targeted drug delivery for the management of oral biofilm-associated infections.展开更多
We demonstrated experimentally the formation of monoenergetic beams of accelerated electrons by focusing femtosecond laser radiation with an intensity of 2×1017W/cm2onto the edge of an aluminum foil.The electrons...We demonstrated experimentally the formation of monoenergetic beams of accelerated electrons by focusing femtosecond laser radiation with an intensity of 2×1017W/cm2onto the edge of an aluminum foil.The electrons had energy distributions peaking in the 0.2–0.8 MeV range with energy spread less than 20%.The acceleration mechanism related to the generation of a plasma wave as a result of self-modulation instability of a laser pulse in a dense plasma formed by a prepulse(arriving 12 ns before the main pulse)is considered.One-dimensional and two-dimensional Particle in Cell(PIC)simulations of the laser–plasma interaction showed that effective excitation of a plasma wave as well as trapping and acceleration of an electron beam with an energy on the order of 1 MeV may occur in the presence of sharp gradients in plasma density and in the temporal shape of the pulse.展开更多
基金This work was supported by National Natural Science Foundation of China(Grant No.21975133,21774062)the Key Projects of Natural Science Foundation of Tianjin,China(19JCZDJC36900)This work is dedicated to the 100th anniversary of Chemistry at Nankai University.
文摘The efficacious delivery of antimicrobial drugs to intractable oral biofilms remains a challenge due to inadequate biofilm penetration and lack of pathogen targeting.Herein,we have developed a microenvironment-activated poly(ethylene glycol)(PEG)-sheddable nanoplatform to mediate targeted delivery of drugs into oral biofilms for the efficient prevention of dental caries.The PEGylated nanoplatform with enhanced biofilm penetration is capable of deshielding the PEG layer under slightly acidic conditions in a PEG chain length-dependent manner to re-expose the bacteria-targeting ligands,thereby facilitating targeted codelivery of ciprofloxacin(CIP)and IR780 to the bacteria after accumulation within biofilms.The nanoplatform tends to induce bacterial agglomeration and suffers from degradation in the acidic oral biofilm microenvironment,triggering rapid drug release on demand around bacterial cells.The self-modulating nanoplatform under near-infrared(NIR)irradiation accordingly displays greatly augmented potency in oral biofilm penetration and disruption compared with drugs alone.Topical oral treatment with nanoplatforms involving synergetic pharmacological and photothermal/photodynamic trinary therapy results in robust biofilm dispersion and efficacious suppression of severe tooth decay in rats.This versatile nanoplatform can promote local accumulation and specific drug transport into biofilms and represents a new paradigm for targeted drug delivery for the management of oral biofilm-associated infections.
基金supported by the programme ‘Extreme Light Fields and Their Applications’ of the Presidium of the Russian Academy of Sciences
文摘We demonstrated experimentally the formation of monoenergetic beams of accelerated electrons by focusing femtosecond laser radiation with an intensity of 2×1017W/cm2onto the edge of an aluminum foil.The electrons had energy distributions peaking in the 0.2–0.8 MeV range with energy spread less than 20%.The acceleration mechanism related to the generation of a plasma wave as a result of self-modulation instability of a laser pulse in a dense plasma formed by a prepulse(arriving 12 ns before the main pulse)is considered.One-dimensional and two-dimensional Particle in Cell(PIC)simulations of the laser–plasma interaction showed that effective excitation of a plasma wave as well as trapping and acceleration of an electron beam with an energy on the order of 1 MeV may occur in the presence of sharp gradients in plasma density and in the temporal shape of the pulse.