Carbon dots(CDs)with precise targeting function show great potential in the field of drug delivery therapeutics.In this study,the functionalized nucleus-targeting orange-emissive CDs with nuclear localization sequence...Carbon dots(CDs)with precise targeting function show great potential in the field of drug delivery therapeutics.In this study,the functionalized nucleus-targeting orange-emissive CDs with nuclear localization sequence(NLS)were loaded with adriamycin(DOX)to obtain a nucleus-targeting orange-emissive CDs drug delivery system(CDs-NLS-DOX),which delivered DOX to tumor cell nuclei to enhance its anti-tumor activity.The drug carrier orange-emissive CDs showed excitation-independent behavior,stable and enhanced imaging capability and good biocompatibility in vitro and in vivo.Meanwhile,the CDs-NLS could target the nuclei efficiently,and the CDs-NLS-DOX complexes had a high drug loading rate(59.4%)after loading DOX,exhibiting p H-dependent DOX release behavior through breaking acylhydrazone bond in a weak acidic environment.In addition,the CDs-NLS-DOX complexes exhibited an enhanced killing activity against human hepatoma cells(HepG2).The in vivo therapeutic effects on HepG2 nude mice transplanted tumors indicated the CDs-NLS-DOX had a stronger ability to inhibit tumor growth compared to free DOX.In short,CDs-NLS-DOX is expected to be a precise and efficient nucleus-targeting nano-drug delivery system for tumor treatment.展开更多
Cancer,a complex and heterogeneous disease,arises from genomic instability.Currently,DNA damage-based cancer treatments,including radiotherapy and chemotherapy,are employed in clinical practice.However,the efficacy an...Cancer,a complex and heterogeneous disease,arises from genomic instability.Currently,DNA damage-based cancer treatments,including radiotherapy and chemotherapy,are employed in clinical practice.However,the efficacy and safety of these therapies are constrained by various factors,limiting their ability to meet current clinical demands.Metal nanoparticles present promising avenues for enhancing each critical aspect of DNA damage-based cancer therapy.Their customizable physicochemical properties enable the development of targeted and personalized treatment platforms.In this review,we delve into the design principles and optimization strategies of metal nanoparticles.We shed light on the limitations of DNA damage-based therapy while highlighting the diverse strategies made possible by metal nanoparticles.These encompass targeted drug delivery,inhibition of DNA repair mechanisms,induction of cell death,and the cascading immune response.Moreover,we explore the pivotal role of physicochemical factors such as nanoparticle size,stimuli-responsiveness,and surface modification in shaping metal nanoparticle platforms.Finally,we present insights into the challenges and future directions of metal nanoparticles in advancing DNA damage-based cancer therapy,paving the way for novel treatment paradigms.展开更多
基金supported by the National Natural Science Foundation of China(Nos.82172048 and U21A20378)Scientific Research Project of Shanxi Provincial Health Commission(No.2023120)+4 种基金Shanxi-Zheda Institute of Advanced Materials and Chemical Engineering(No.2021SX-FR010)Shanxi Center of Technology Innovation for Controlled and Sustained Release of Nanodrugs(No.202104010911026)Foundational Research Project of Shanxi Province(No.202203021211159)Four“Batches”Innovation Project of Invigorating Medical through Science and Technology of Shanxi Province(No.2023XM012)Shanxi Scholarship Council of China(No.2022–039)。
文摘Carbon dots(CDs)with precise targeting function show great potential in the field of drug delivery therapeutics.In this study,the functionalized nucleus-targeting orange-emissive CDs with nuclear localization sequence(NLS)were loaded with adriamycin(DOX)to obtain a nucleus-targeting orange-emissive CDs drug delivery system(CDs-NLS-DOX),which delivered DOX to tumor cell nuclei to enhance its anti-tumor activity.The drug carrier orange-emissive CDs showed excitation-independent behavior,stable and enhanced imaging capability and good biocompatibility in vitro and in vivo.Meanwhile,the CDs-NLS could target the nuclei efficiently,and the CDs-NLS-DOX complexes had a high drug loading rate(59.4%)after loading DOX,exhibiting p H-dependent DOX release behavior through breaking acylhydrazone bond in a weak acidic environment.In addition,the CDs-NLS-DOX complexes exhibited an enhanced killing activity against human hepatoma cells(HepG2).The in vivo therapeutic effects on HepG2 nude mice transplanted tumors indicated the CDs-NLS-DOX had a stronger ability to inhibit tumor growth compared to free DOX.In short,CDs-NLS-DOX is expected to be a precise and efficient nucleus-targeting nano-drug delivery system for tumor treatment.
基金funded by National Key Research and Development Program of China(2022YFB3203804,2022YFB3203801,2022YFB3203800)the Leading Talent of“Ten Thousand Plan”National High-Level Talents Special Support Plan,National Natural Science Foundation of China(32071374,32000985)+4 种基金Program of Shanghai Academic Research Leader under the Science and Technology Innovation Action Plan(21XD1422100,China)Program of Shanghai Science and Technology Development(22TS1400700,China)Zhejiang Provincial Natural Science Foundation of China(LR22C100001,LQ21H300003,China)Innovative Research Team of High-Level Local Universities in Shanghai(SHSMU-ZDCX20210900,China)CAS Interdisciplinary Innovation Team(JCTD-2020-08,China)。
文摘Cancer,a complex and heterogeneous disease,arises from genomic instability.Currently,DNA damage-based cancer treatments,including radiotherapy and chemotherapy,are employed in clinical practice.However,the efficacy and safety of these therapies are constrained by various factors,limiting their ability to meet current clinical demands.Metal nanoparticles present promising avenues for enhancing each critical aspect of DNA damage-based cancer therapy.Their customizable physicochemical properties enable the development of targeted and personalized treatment platforms.In this review,we delve into the design principles and optimization strategies of metal nanoparticles.We shed light on the limitations of DNA damage-based therapy while highlighting the diverse strategies made possible by metal nanoparticles.These encompass targeted drug delivery,inhibition of DNA repair mechanisms,induction of cell death,and the cascading immune response.Moreover,we explore the pivotal role of physicochemical factors such as nanoparticle size,stimuli-responsiveness,and surface modification in shaping metal nanoparticle platforms.Finally,we present insights into the challenges and future directions of metal nanoparticles in advancing DNA damage-based cancer therapy,paving the way for novel treatment paradigms.