Dry powder inhalation represents a promising approach for the treatment of lung cancer,offering several advantages such as enhanced targeting,improved bioavailability,and reduced toxicity.However,traditional dry powde...Dry powder inhalation represents a promising approach for the treatment of lung cancer,offering several advantages such as enhanced targeting,improved bioavailability,and reduced toxicity.However,traditional dry powder formulations suffer from limitations,notably low pulmonary delivery efficiency and inadequate penetration into tumor tissues,thereby limiting their therapeutic efficacy.In response to these challenges,we have developed an innovative trojan horse strategy,harnessing an inhalable nanoparticlein-microsphere system characterized by tunable size,reversible charge,and mucus-penetrating capabilities.The inhalable nanoparticle-in-microsphere system exhibit stable structural properties,excellent environmental responsiveness and high biocompatibility.More importantly,the therapeutic effect of MTX@PAMAM@HA@Gel(MPHG)was demonstrated in vitro and in vivo.This system offers improved pulmonary delivery efficiency,enhanced drug retention within tumor tissues,and effective penetration,thus representing a promising strategy in lung cancer treatment.展开更多
The exsolution method has garnered significant attention owing to its high efficacy in developing highly efficient and stable metal nanocatalysts.Herein,a versatile exsolution approach is developed to embed size-tunab...The exsolution method has garnered significant attention owing to its high efficacy in developing highly efficient and stable metal nanocatalysts.Herein,a versatile exsolution approach is developed to embed size-tunable metal nanocatalysts within a conductive metal pnictogenide matrix.The gas-phase reaction of Ru-substituted Ni-Fe-layered-double-hydroxide(Ni_(2)Fe_(1-x)Ru_(x)-LDH)with pnictogenation reagents leads to the exsolution of Ru metal nanocatalysts and a phase transformation into metal pnictogenide.The variation in reactivity of pnictogenation reagents allows for control over the size of the exsolved metal nanocatalysts(i.e.,nanoclusters for nitridation and single atoms for phosphidation),underscoring the effectiveness of the pnictogenation-driven exsolution strategy in stabilizing size-tunable metal nanocatalysts.The Ru-exsolved nickel-iron nitride/phosphide demonstrates outstanding electrocatalyst activity for the hydrogen evolution reaction,exhibiting a smaller overpotential and higher stability than Ru-deposited homologs.The high efficacy of pnictogenation-assisted exsolution in optimizing the performance and stability of Ru metal nanocatalysts is ascribed to the efficient interfacial electronic interaction between Ru metals and nitride/phosphide ions assisted by the inner sphere mechanism.In situ spectroscopic analyses highlight that exsolved Ru single atoms facilitate more efficient electron transfer to the reactants than the exsolved Ru nanoclusters,which is primarily responsible for the superior impact of the phosphidation-driven exsolution approach.展开更多
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
As a typical human pathogenic fungus,Cryptococcus neoformans is a life-threatening invasive fungal pathogen with a worldwide distribution causing w700,000 deaths annually.Cryptococcosis is not just an infection with m...As a typical human pathogenic fungus,Cryptococcus neoformans is a life-threatening invasive fungal pathogen with a worldwide distribution causing w700,000 deaths annually.Cryptococcosis is not just an infection with multi-organ involvement,intracellular survival and extracellular multiplication of the fungus also play important roles in the pathogenesis of C.neoformans infections.Because adequate accumulation of drugs at target organs and cells is still difficult to achieve,an effective delivery strategy is desperately required to treat these infections.Here,we report a bioresponsive micro-to-nano(MTN)system that effectively clears the C.neoformans in vivo.This strategy is based on our in-depth study of the overexpression of matrix metalloproteinase 3(MMP-3)in infectious microenvironments(IMEs)and secreted protein acidic and rich in cysteine(SPARC)in several associated target cells.In this MTN system,bovine serum albumin(BSA,a natural ligand of SPARC)was used for the preparation of nanoparticles(NPs),and then microspheres were constructed by conjugation with a special linker,which mainly consisted of a BSA-binding peptide and an MMP-3-responsive peptide.This MTN system was mechanically captured by the smallest capillaries of the lungs after intravenous injection,and then hydrolyzed into BSA NPs by MMP-3 in the IMEs.The NPs further targeted the lung tissue,brain and infected macrophages based on the overexpression of SPARC,reaching multiple targets and achieving efficient treatment.We have developed a size-tunable strategy where microspheres"shrink"to NPs in IMEs,which effectively combines active and passive targeting and may be especially powerful in the fight against complex fungal infections.展开更多
基金supported by the National Natural Science Foundation of China(No.52273123)the Natural Science Foundation of Chongqing,China(No.CSTB2022NSCQ-MSX0474)the Talent-introduction Program of Chongqing Medical and Pharmaceutical College(No.YGZRC2023103).
文摘Dry powder inhalation represents a promising approach for the treatment of lung cancer,offering several advantages such as enhanced targeting,improved bioavailability,and reduced toxicity.However,traditional dry powder formulations suffer from limitations,notably low pulmonary delivery efficiency and inadequate penetration into tumor tissues,thereby limiting their therapeutic efficacy.In response to these challenges,we have developed an innovative trojan horse strategy,harnessing an inhalable nanoparticlein-microsphere system characterized by tunable size,reversible charge,and mucus-penetrating capabilities.The inhalable nanoparticle-in-microsphere system exhibit stable structural properties,excellent environmental responsiveness and high biocompatibility.More importantly,the therapeutic effect of MTX@PAMAM@HA@Gel(MPHG)was demonstrated in vitro and in vivo.This system offers improved pulmonary delivery efficiency,enhanced drug retention within tumor tissues,and effective penetration,thus representing a promising strategy in lung cancer treatment.
基金supported by the National Research Foundation of Korea(NRF)grant funded by the Korean government(MSIT)(RS-2023-00208355,RS-2024-00439825,and 2022M3H4A408610313)supported by the Global Science Research Center Program(RS-2024-00411134)+1 种基金funded by the National Research Foundation of KoreaThe experiments at PAL were supported in part by MOST and POSTECH。
文摘The exsolution method has garnered significant attention owing to its high efficacy in developing highly efficient and stable metal nanocatalysts.Herein,a versatile exsolution approach is developed to embed size-tunable metal nanocatalysts within a conductive metal pnictogenide matrix.The gas-phase reaction of Ru-substituted Ni-Fe-layered-double-hydroxide(Ni_(2)Fe_(1-x)Ru_(x)-LDH)with pnictogenation reagents leads to the exsolution of Ru metal nanocatalysts and a phase transformation into metal pnictogenide.The variation in reactivity of pnictogenation reagents allows for control over the size of the exsolved metal nanocatalysts(i.e.,nanoclusters for nitridation and single atoms for phosphidation),underscoring the effectiveness of the pnictogenation-driven exsolution strategy in stabilizing size-tunable metal nanocatalysts.The Ru-exsolved nickel-iron nitride/phosphide demonstrates outstanding electrocatalyst activity for the hydrogen evolution reaction,exhibiting a smaller overpotential and higher stability than Ru-deposited homologs.The high efficacy of pnictogenation-assisted exsolution in optimizing the performance and stability of Ru metal nanocatalysts is ascribed to the efficient interfacial electronic interaction between Ru metals and nitride/phosphide ions assisted by the inner sphere mechanism.In situ spectroscopic analyses highlight that exsolved Ru single atoms facilitate more efficient electron transfer to the reactants than the exsolved Ru nanoclusters,which is primarily responsible for the superior impact of the phosphidation-driven exsolution approach.
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.82073789,and 81673376)the project for Innovative Research Group at Higher Educational Institutions in Chongqing(CXQT20006,China)+1 种基金Chongqing Postgraduate Research and Innovation Project(CYB20106,China)CAS Interdiscipliary Innovation Team(China)。
文摘As a typical human pathogenic fungus,Cryptococcus neoformans is a life-threatening invasive fungal pathogen with a worldwide distribution causing w700,000 deaths annually.Cryptococcosis is not just an infection with multi-organ involvement,intracellular survival and extracellular multiplication of the fungus also play important roles in the pathogenesis of C.neoformans infections.Because adequate accumulation of drugs at target organs and cells is still difficult to achieve,an effective delivery strategy is desperately required to treat these infections.Here,we report a bioresponsive micro-to-nano(MTN)system that effectively clears the C.neoformans in vivo.This strategy is based on our in-depth study of the overexpression of matrix metalloproteinase 3(MMP-3)in infectious microenvironments(IMEs)and secreted protein acidic and rich in cysteine(SPARC)in several associated target cells.In this MTN system,bovine serum albumin(BSA,a natural ligand of SPARC)was used for the preparation of nanoparticles(NPs),and then microspheres were constructed by conjugation with a special linker,which mainly consisted of a BSA-binding peptide and an MMP-3-responsive peptide.This MTN system was mechanically captured by the smallest capillaries of the lungs after intravenous injection,and then hydrolyzed into BSA NPs by MMP-3 in the IMEs.The NPs further targeted the lung tissue,brain and infected macrophages based on the overexpression of SPARC,reaching multiple targets and achieving efficient treatment.We have developed a size-tunable strategy where microspheres"shrink"to NPs in IMEs,which effectively combines active and passive targeting and may be especially powerful in the fight against complex fungal infections.
