The application of nanotechnologies in formulation has significantly promoted the development of modern medical and pharmacological science, especially for nanoparticle-based drug delivery, bioimaging, and theranostic...The application of nanotechnologies in formulation has significantly promoted the development of modern medical and pharmacological science, especially for nanoparticle-based drug delivery, bioimaging, and theranostics. The advancement of engineering particle design and fabrication is largely supported by a better understanding of how their apparent characteristics(e.g., size and size distribution, surface morphology, colloidal stability, chemical composition) influence their in vivo biological performance, which raises an urgent need for practical nanoformulation methods. Based on turbulent flow mixing and the self-assembly of molecules in fluids, flash technologies emerged as effective bottom-up fabrication strategies for effective nanoformulation. Among the flash technology family, flash nanocomplexation(FNC) is considered a novel and promising candidate that can promote and optimize formulation processes in a precise spatiotemporal manner, thus obtaining excellent fabrication efficiency, reproducibility and expandability. This review presents an overview of recent advances in fabricating drug-delivery nanoparticles using FNC platforms. Firstly, brief introductions to the basic principles of FNC technology were carried out, followed by descriptions of turbulent microvolume mixers that have significantly promoted the efficiency of FNC-based fabrications. Applications of real formulation cases were then categorized according to the self-assembly-driven interactions(including electrostatic interaction, coordination interaction,hydrogen bonding and hydrophobic interaction) and discussed to reveal the progressiveness of fabricating nanoparticles and discuss how its flexibility will provide advances and replenish the philosophy of nanomedicine formulation. In the end, the commercial potential, current limitations, and prospects of FNC technology for nanoformulation will be summarized and discussed.展开更多
Bacterial pneumonia is the most common infectious disease with high morbidity and short-term mortality.The key to the treatment of bacterial pneumonia is rapid clearance of the pathogen and effective control of the in...Bacterial pneumonia is the most common infectious disease with high morbidity and short-term mortality.The key to the treatment of bacterial pneumonia is rapid clearance of the pathogen and effective control of the inflammatory response.In this study,a disulfide-bonded hydroxyl-rich hyperbranched polyaminoglycosides of tobramycin(SS-HPT)was synthesized.SS-HPT could be electrostatically complexed with plasmid DNA(pDNA)encoding heme oxygenase-1(pHO-1)to form complexes nanoparticles(HPT/HO),which successfully achieved efficient intracellular delivery of pHO-1.HPT/HO exhibited broadspectrum antibacterial properties,good cytotoxicity,highly efficient reactive oxygen species(ROS)scavenging capacity,and effective anti-inflammatory properties.In addition,HPT/HO exhibited good bacteriostatic properties and effective transfection in the lungs of Methicillin-resistant Staphylococcus aureus(MRSA)-infected pneumonia mice,alleviated the cytokine storm and oxidative stress levels in the lungs,suppressed the over-activated inflammatory response,avoided the generation of lung injury,and improved the survival rate of mice.This study provided an antimicrobial gene carrier that provides a reliable target and effective method for the clinical treatment of MRSA pneumonia.展开更多
The dramatic increase of microbial resistances against conventional available antibiotics is a huge challenge to the effective treatment of infectious disease and thus becoming a daunting global threat of major concer...The dramatic increase of microbial resistances against conventional available antibiotics is a huge challenge to the effective treatment of infectious disease and thus becoming a daunting global threat of major concern,which necessitates the development of innovative therapeutics.Nanomaterial-based antimicrobial strategies have emerged as novel and promising tools to combat lethal bacteria and recalcitrant biofilm,featuring the abilities to evade existing drug resistance-related mechanisms.In this review,recent advances in“state-of-the-art”nanosystems which acting either as inherent therapeutics or nanocarriers for the precise delivery of antibiotics,are comprehensively summarized.Those nanosystems can effectively accumulate at the infectious sites,achieve multifunctional synergistic antibacterial efficacy,and provide controlled release of antibiotics in response to endogenous or exogenous stimulus(e.g.,low pH,enzymes,or illumination).Especially,the nanoplatform that integrated with photothermal/photodynamic therapy(PTT/PDT)can enhance the bacterial destruction and biofilm penetration or ablation.In addition,nanoparticle-based approaches with enzymatically promoting bacterial killing,anti-virulence,and other mechanisms were also involved.Overall,this review provides crucial insights into the recent progress and remaining limitations of various antimicrobial nanotherapeutic strategies,and enlightens the further developments in this field simultaneously,which eventually benefiting public health.展开更多
Liver injury,caused by factors like viral hepatitis and drug overdose,poses a significant health risk,with current diagnostic methods lacking specificity,increasing the need for more precise molecular imaging techniqu...Liver injury,caused by factors like viral hepatitis and drug overdose,poses a significant health risk,with current diagnostic methods lacking specificity,increasing the need for more precise molecular imaging techniques.Herein,we present an activatable semiconducting liver injury reporter(SLIR)for early and accurate diagnosis of liver injury.The SLIR,which is composed of semiconducting polymers with an electronwithdrawing quenching segment,remains nonfluorescent until it encounters biothiols such as cysteine in the liver.SLIR accumulates efficiently in the liver and respond rapidly to biothiols,allowing accurate and early detection of liver damage.The recovery of SLIR fluorescence negatively reflects the dynamics of oxidative stress in the liver and provides information on the severity of tissue damage.Thus,the specificity of SLIR,the fast response,and the efficient targeting of the liver make it a promising tool for the precise diagnosis of liver damage at an early stage.展开更多
基金supported by the Sanya Yazhou Bay Science and Technology City (No. 2021JJLH0037)Taishan Scholar Foundation of Shandong Province (No. tsqn202211065)+2 种基金Natural Science Foundation of China (No. 82003673)Yangcheng Scholars Research Project of Guangzhou (No. 20183197)Guangzhou Science and Technology Plan (No. 201901010170)
文摘The application of nanotechnologies in formulation has significantly promoted the development of modern medical and pharmacological science, especially for nanoparticle-based drug delivery, bioimaging, and theranostics. The advancement of engineering particle design and fabrication is largely supported by a better understanding of how their apparent characteristics(e.g., size and size distribution, surface morphology, colloidal stability, chemical composition) influence their in vivo biological performance, which raises an urgent need for practical nanoformulation methods. Based on turbulent flow mixing and the self-assembly of molecules in fluids, flash technologies emerged as effective bottom-up fabrication strategies for effective nanoformulation. Among the flash technology family, flash nanocomplexation(FNC) is considered a novel and promising candidate that can promote and optimize formulation processes in a precise spatiotemporal manner, thus obtaining excellent fabrication efficiency, reproducibility and expandability. This review presents an overview of recent advances in fabricating drug-delivery nanoparticles using FNC platforms. Firstly, brief introductions to the basic principles of FNC technology were carried out, followed by descriptions of turbulent microvolume mixers that have significantly promoted the efficiency of FNC-based fabrications. Applications of real formulation cases were then categorized according to the self-assembly-driven interactions(including electrostatic interaction, coordination interaction,hydrogen bonding and hydrophobic interaction) and discussed to reveal the progressiveness of fabricating nanoparticles and discuss how its flexibility will provide advances and replenish the philosophy of nanomedicine formulation. In the end, the commercial potential, current limitations, and prospects of FNC technology for nanoformulation will be summarized and discussed.
基金supported by the National Key Research and Development Program of China(2021YFB3800900)the National Natural Science Foundation of China(51925305,52433006,52495010,52495015,52303381)+3 种基金the Natural Science Foundation of Xiamen,China(3502Z202371003)the Fundamental Research Funds for the Central Universities(20720230008)the Talent Cultivation Project Funds for the Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province(HRTP-[2022]52)The study described was supported by grants from the project supported by the General Plan Project of Quanzhou,Fujian Province,China(2024NS009[to N Dong])。
文摘Bacterial pneumonia is the most common infectious disease with high morbidity and short-term mortality.The key to the treatment of bacterial pneumonia is rapid clearance of the pathogen and effective control of the inflammatory response.In this study,a disulfide-bonded hydroxyl-rich hyperbranched polyaminoglycosides of tobramycin(SS-HPT)was synthesized.SS-HPT could be electrostatically complexed with plasmid DNA(pDNA)encoding heme oxygenase-1(pHO-1)to form complexes nanoparticles(HPT/HO),which successfully achieved efficient intracellular delivery of pHO-1.HPT/HO exhibited broadspectrum antibacterial properties,good cytotoxicity,highly efficient reactive oxygen species(ROS)scavenging capacity,and effective anti-inflammatory properties.In addition,HPT/HO exhibited good bacteriostatic properties and effective transfection in the lungs of Methicillin-resistant Staphylococcus aureus(MRSA)-infected pneumonia mice,alleviated the cytokine storm and oxidative stress levels in the lungs,suppressed the over-activated inflammatory response,avoided the generation of lung injury,and improved the survival rate of mice.This study provided an antimicrobial gene carrier that provides a reliable target and effective method for the clinical treatment of MRSA pneumonia.
基金This work was supported by the Natural Science Foundation of China(No.82003673)National Key R&D Program of China(Nos.2019YFC0312101 and 2019YFC0312102).
文摘The dramatic increase of microbial resistances against conventional available antibiotics is a huge challenge to the effective treatment of infectious disease and thus becoming a daunting global threat of major concern,which necessitates the development of innovative therapeutics.Nanomaterial-based antimicrobial strategies have emerged as novel and promising tools to combat lethal bacteria and recalcitrant biofilm,featuring the abilities to evade existing drug resistance-related mechanisms.In this review,recent advances in“state-of-the-art”nanosystems which acting either as inherent therapeutics or nanocarriers for the precise delivery of antibiotics,are comprehensively summarized.Those nanosystems can effectively accumulate at the infectious sites,achieve multifunctional synergistic antibacterial efficacy,and provide controlled release of antibiotics in response to endogenous or exogenous stimulus(e.g.,low pH,enzymes,or illumination).Especially,the nanoplatform that integrated with photothermal/photodynamic therapy(PTT/PDT)can enhance the bacterial destruction and biofilm penetration or ablation.In addition,nanoparticle-based approaches with enzymatically promoting bacterial killing,anti-virulence,and other mechanisms were also involved.Overall,this review provides crucial insights into the recent progress and remaining limitations of various antimicrobial nanotherapeutic strategies,and enlightens the further developments in this field simultaneously,which eventually benefiting public health.
基金National Natural Science Foundation of China(52303381,51925305)Natural Science Foundation of Xiamen,China(3502Z202371003)+1 种基金National Key Research and Development Program of China the Central Universities(20720230008)the talent cultivation project Funds for the Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province(HRTP-[2022]52).
文摘Liver injury,caused by factors like viral hepatitis and drug overdose,poses a significant health risk,with current diagnostic methods lacking specificity,increasing the need for more precise molecular imaging techniques.Herein,we present an activatable semiconducting liver injury reporter(SLIR)for early and accurate diagnosis of liver injury.The SLIR,which is composed of semiconducting polymers with an electronwithdrawing quenching segment,remains nonfluorescent until it encounters biothiols such as cysteine in the liver.SLIR accumulates efficiently in the liver and respond rapidly to biothiols,allowing accurate and early detection of liver damage.The recovery of SLIR fluorescence negatively reflects the dynamics of oxidative stress in the liver and provides information on the severity of tissue damage.Thus,the specificity of SLIR,the fast response,and the efficient targeting of the liver make it a promising tool for the precise diagnosis of liver damage at an early stage.