Insufficient intratumoral retention of nanomedicines remains the major challenge for broad implementation in clinical sets.Herein,we proposed a legumain-triggered aggregable gold nanoparticle(GNP)delivery platform(GNP...Insufficient intratumoral retention of nanomedicines remains the major challenge for broad implementation in clinical sets.Herein,we proposed a legumain-triggered aggregable gold nanoparticle(GNP)delivery platform(GNPs-A&C).GNPs-A&C could form intratumoral or intracellular aggregates in response to the overexpressed legumain.The aggregates with size increase not only could reduce back-flow from interstitial space to peripheral bloodstream but also could restrict the cellular exocytosis,leading to enhanced intratumoral retention.In vitro studies demonstrated that GNPs-A&C possessed an excellent legumain responsiveness and the increased size was closely relevant with legumain expression.In vivo studies demonstrated GNPs-A&C possessed slower clearance rate and much higher intratumoral retention within legumain-overexpressed tumor compared to non-aggregable NPs,regardless of intravenous or intratumoral injection.More importantly,this delivery platform significantly improved the chemotherapeutic effect of doxorubicin(DOX)towards subcutaneous xenograft C6 tumor.The effectiveness of this stimulus-responsive aggregable delivery system provides a thinking for designing more intelligent size-tunable nanomedicine that can substantially improve intratumoral retention.展开更多
Recent days,aggregatable nanoparticles,which can specifically respond to certain stimulus,have shown great potential in tumor-targeted drug delivery with prolonged retention and deeper penetration.In this review,we su...Recent days,aggregatable nanoparticles,which can specifically respond to certain stimulus,have shown great potential in tumor-targeted drug delivery with prolonged retention and deeper penetration.In this review,we summarize recent advances in design of aggregatable nanoparticles by different stimuli.Internal(pH and enzyme)and external(light,temperature and ROS)stimuli are introduced for a comprehensive description.Moreover,the aggregated nanoparticles usually exhibit photothermal,photoacoustic,PET and enhanced MRI contrast,which is also described.In the end,we discuss about the potential applications and challenges for the future clinical translation.展开更多
基金supported by the Beijing Natural Science Foundation(No.L222128)Beijing Institute of Technology Research Fund Program for Young Scholars(No.XSQD-202121010)National Natural Science Foundation of China(No.81961138009)。
文摘Insufficient intratumoral retention of nanomedicines remains the major challenge for broad implementation in clinical sets.Herein,we proposed a legumain-triggered aggregable gold nanoparticle(GNP)delivery platform(GNPs-A&C).GNPs-A&C could form intratumoral or intracellular aggregates in response to the overexpressed legumain.The aggregates with size increase not only could reduce back-flow from interstitial space to peripheral bloodstream but also could restrict the cellular exocytosis,leading to enhanced intratumoral retention.In vitro studies demonstrated that GNPs-A&C possessed an excellent legumain responsiveness and the increased size was closely relevant with legumain expression.In vivo studies demonstrated GNPs-A&C possessed slower clearance rate and much higher intratumoral retention within legumain-overexpressed tumor compared to non-aggregable NPs,regardless of intravenous or intratumoral injection.More importantly,this delivery platform significantly improved the chemotherapeutic effect of doxorubicin(DOX)towards subcutaneous xenograft C6 tumor.The effectiveness of this stimulus-responsive aggregable delivery system provides a thinking for designing more intelligent size-tunable nanomedicine that can substantially improve intratumoral retention.
基金supported by the National Natural Science Foundation of China(No.81961138009)the Young Elite Scientists Sponsorship Program by CAST(No.2017QNR001)+1 种基金the Fundamental Research Funds for the Central Universities,111 Project(No.B18035)RFBR and National Natural Science Foundation of China Collaboration Project(No.19-58-55001)。
文摘Recent days,aggregatable nanoparticles,which can specifically respond to certain stimulus,have shown great potential in tumor-targeted drug delivery with prolonged retention and deeper penetration.In this review,we summarize recent advances in design of aggregatable nanoparticles by different stimuli.Internal(pH and enzyme)and external(light,temperature and ROS)stimuli are introduced for a comprehensive description.Moreover,the aggregated nanoparticles usually exhibit photothermal,photoacoustic,PET and enhanced MRI contrast,which is also described.In the end,we discuss about the potential applications and challenges for the future clinical translation.
