Catalysis-based chemodynamic therapy(CDT)is an emerging cancer treatment strategy which uses a Fenton-like reaction to kill tumor cells by catalyzing endogenous hydrogen peroxide(H_(2)O_(2))into a toxic hydroxyl radic...Catalysis-based chemodynamic therapy(CDT)is an emerging cancer treatment strategy which uses a Fenton-like reaction to kill tumor cells by catalyzing endogenous hydrogen peroxide(H_(2)O_(2))into a toxic hydroxyl radical(·OH).The performance of CDT is greatly dependent on PDT agent.Herein,mitochondria-targeting Pt nanoclusters were synthesized using cytochrome c aptamer(CytcApt)as template.The obtained CytcApt-PtNCs can produce.OH by H_(2)O_(2)under the acidic conditions.Moreover,CytcApt-PtNCs could kill 4T1 tumor cells in a pH-dependent manner,but had no side effect on normal 293T cells.Therefore,CytcApt-PtNCs possess excellent therapeutic effect and good biosafety,indicating their great potential for CDT.展开更多
Selective activation of Pt(Ⅳ)prodrugs within tumors has emerged as a promising strategy in tumor treatment.Although progress has been made with photo-and ultrasound-activated Pt(Ⅳ)prodrugs,concerns remain over the n...Selective activation of Pt(Ⅳ)prodrugs within tumors has emerged as a promising strategy in tumor treatment.Although progress has been made with photo-and ultrasound-activated Pt(Ⅳ)prodrugs,concerns remain over the non-specific activation of photosensitizers(PS)and the potential for phototoxicity and chemical toxicity.In this study,a sequential dual-locked Pt(Ⅳ)nano-prodrug that can be activated by both the acidic tumor microenvironment and light was developed.The Pt(Ⅳ)prodrug was prepared by conjugating PS-locked Pt(Ⅳ)to a polymeric core,which was then chelated with metallo iron to lock its photoactivity and form a metallo-nano prodrug.Under acidic tumor microenvironment conditions,the metallo-nano prodrug undergoes dissociation of iron,triggering a reduction process in oxaliplatin under light irradiation,resulting in the activation of both chemotherapy and photodynamic therapy(PDT).Additionally,the prodrug could induce metallo-triggered ferroptosis and polarization of tumorassociated macrophages(TAM),thereby enhancing tumor inhibition.The dual-lock strategy employed in a nanoparticle delivery system represents an expansion in the application of platinum-based anticancer drugs,making it a promising new direction in cancer treatment.展开更多
A standard in-beam y-spectroscopy experiment for ^188Pt is performed via the ^176yb（^18O, 6n） reaction at beam energies of 88 and 95 MeV, and the level scheme for ^188Pt is established. Prolate and oblate shape coex...A standard in-beam y-spectroscopy experiment for ^188Pt is performed via the ^176yb（^18O, 6n） reaction at beam energies of 88 and 95 MeV, and the level scheme for ^188Pt is established. Prolate and oblate shape coexistence has been demonstrated to occur in ^188Pt by applying the projected shell model. The rotation Mignment of i13/2 neutrons drives the yrast sequence changing suddenly from prolate to oblate shape at angular momentum 1Oh, indicating likely a new type of shape phase transition along the yrast fine in ^188Pt.展开更多
CRISPR/Cas9 system has become a promising gene editing tool for cancer treatment.However,development of a simple and effective nanocarrier to incorporate CRISPR/Cas9 system and chemotherapeutic drugs to concurrently t...CRISPR/Cas9 system has become a promising gene editing tool for cancer treatment.However,development of a simple and effective nanocarrier to incorporate CRISPR/Cas9 system and chemotherapeutic drugs to concurrently tackle the biological safety and packaging capacity of viral vectors and combine gene editing-chemo for cancer therapy still remains challenges.Herein,a chain-shattering Pt(IV)-backboned polymeric nanoplatform is developed for the delivery of EZH2-targeted CRISPR/Cas9 system(NPCSPt/pEZH2)and synergistic treatment of prostate cancer.The pEZH2/Pt(II)could be effectively triggered to unpack/release from NPCSPt/pEZH2 in a chain-shattering manner in cancer cells.The EZH2 gene disruption efficiency could be achieved up to 32.2%of PC-3 cells in vitro and 21.3%of tumor tissues in vivo,leading to effective suppression of EZH2 protein expression.Moreover,significant H3K27me3 downregulation could occur after EZH2 suppression,resulting in a more permissive chromatin structure that increases the accessibility of released Pt(II)to nuclear DNA for enhanced apoptosis.Taken together,substantial proliferation inhibition of prostate cancer cells and further 85.4%growth repression against subcutaneous xenograft tumor could be achieved.This chain-shattering Pt(IV)-backboned polymeric nanoplatform system not only provides a prospective nanocarrier for CRISPR/Cas9 system delivery,but also broadens the potential of combining gene editing-chemo synergistic cancer therapy.展开更多
Platinum(Pt) based drugs, such as cisplatin, are widely used as anti-cancer agents, but their severe adverse reactions and resistance of cancer patients have limited their board clinical use. For the last few decades,...Platinum(Pt) based drugs, such as cisplatin, are widely used as anti-cancer agents, but their severe adverse reactions and resistance of cancer patients have limited their board clinical use. For the last few decades, Pt(Ⅱ) compounds, Pt(Ⅳ) prodrugs as well as smart drug delivery systems have been developed to overcome these problems. However, most conventional strategies rely on the similar anti-cancer mechanism with cisplatin and consequently only achieve limited success. Recently, Pt nanocrystals/nanoclusters(Pt NCs), with a brand new anti-cancer mechanism, have shown a promising potential in targeted cancer therapy, especially in Pt resistance circumvention. This review is helpful to understand the research strategies of Pt drugs, particularly, the recent developments and medical applications of Pt NCs.展开更多
Distinctively different metabolism between tumor cells and normal cells endows tumor tissues unique microenvironment.In this regard,we have successfully prepared a sequential catalytic platform based on Au/Pt star for...Distinctively different metabolism between tumor cells and normal cells endows tumor tissues unique microenvironment.In this regard,we have successfully prepared a sequential catalytic platform based on Au/Pt star for tumor theragnostic.The multifunctional probes consisted of a gold/platinum star-shaped core(Au/Pt star)conjugated with a GSH-sensitive disulfide bond(S–S),a targeting ligand(rHSA-FA),a near-infrared fluorophore(IR780)and glucose oxidase(GOx).When systemically administered in a xenografted murine model,the probes specifically targeted the tumor sites.As the disulfide linker was cleaved by intracellular GSH,the IR780 molecules could be released for photo-thermal therapy&photodynamic therapy(PTT&PDT)and imaging.Subsequently,the Pt nanolayer of the Au/Pt star and the GOx formed a sequential catalytic system:GOx effectively catalyzed intracellular glucose by consuming oxygen to generate H2O2 and enhance the local acidity,and the Pt layer exhibited peroxidase-like property to catalyze H2O2 producing toxic·OH for tumor oxidative damage.Here we demonstrated that our probes simultaneously possessed a GSH-sensitive release,real-time imaging ability,and synergetic cancer starving-like therapy/enzyme oxidative therapy/PTT/PDT features,which provides a potential strategy for effective tumor theragnostic.展开更多
基金This work is supported by the Cross Research Fund of Biomedical Engineering of Shanghai Jiao Tong University(YG2019QNA43).
文摘Catalysis-based chemodynamic therapy(CDT)is an emerging cancer treatment strategy which uses a Fenton-like reaction to kill tumor cells by catalyzing endogenous hydrogen peroxide(H_(2)O_(2))into a toxic hydroxyl radical(·OH).The performance of CDT is greatly dependent on PDT agent.Herein,mitochondria-targeting Pt nanoclusters were synthesized using cytochrome c aptamer(CytcApt)as template.The obtained CytcApt-PtNCs can produce.OH by H_(2)O_(2)under the acidic conditions.Moreover,CytcApt-PtNCs could kill 4T1 tumor cells in a pH-dependent manner,but had no side effect on normal 293T cells.Therefore,CytcApt-PtNCs possess excellent therapeutic effect and good biosafety,indicating their great potential for CDT.
基金supported by the Jiangsu Province Postgraduate Research Innovation Program and Jiangsu Province Postgraduate Practice Innovation Program Fund(021093002589,China)National Key Research and Development Program of China(2023YFB3813001)National Natural Science Foundation of China(52073145).
文摘Selective activation of Pt(Ⅳ)prodrugs within tumors has emerged as a promising strategy in tumor treatment.Although progress has been made with photo-and ultrasound-activated Pt(Ⅳ)prodrugs,concerns remain over the non-specific activation of photosensitizers(PS)and the potential for phototoxicity and chemical toxicity.In this study,a sequential dual-locked Pt(Ⅳ)nano-prodrug that can be activated by both the acidic tumor microenvironment and light was developed.The Pt(Ⅳ)prodrug was prepared by conjugating PS-locked Pt(Ⅳ)to a polymeric core,which was then chelated with metallo iron to lock its photoactivity and form a metallo-nano prodrug.Under acidic tumor microenvironment conditions,the metallo-nano prodrug undergoes dissociation of iron,triggering a reduction process in oxaliplatin under light irradiation,resulting in the activation of both chemotherapy and photodynamic therapy(PDT).Additionally,the prodrug could induce metallo-triggered ferroptosis and polarization of tumorassociated macrophages(TAM),thereby enhancing tumor inhibition.The dual-lock strategy employed in a nanoparticle delivery system represents an expansion in the application of platinum-based anticancer drugs,making it a promising new direction in cancer treatment.
基金Supported by the Major State Basic Research Programme of China 2007CB815001, the National Natural Science Foundation of China under Grant No 10775158, and the Chinese Academy of Sciences.
文摘A standard in-beam y-spectroscopy experiment for ^188Pt is performed via the ^176yb（^18O, 6n） reaction at beam energies of 88 and 95 MeV, and the level scheme for ^188Pt is established. Prolate and oblate shape coexistence has been demonstrated to occur in ^188Pt by applying the projected shell model. The rotation Mignment of i13/2 neutrons drives the yrast sequence changing suddenly from prolate to oblate shape at angular momentum 1Oh, indicating likely a new type of shape phase transition along the yrast fine in ^188Pt.
基金The authors acknowledge the financial support from National Natural Science Foundation of China(Grant Nos.51773198,51673188,and 21975246)The animal study protocol was approved by the Institutional Animal Care and Use Committee at Chinese Academy of Sciences.
文摘CRISPR/Cas9 system has become a promising gene editing tool for cancer treatment.However,development of a simple and effective nanocarrier to incorporate CRISPR/Cas9 system and chemotherapeutic drugs to concurrently tackle the biological safety and packaging capacity of viral vectors and combine gene editing-chemo for cancer therapy still remains challenges.Herein,a chain-shattering Pt(IV)-backboned polymeric nanoplatform is developed for the delivery of EZH2-targeted CRISPR/Cas9 system(NPCSPt/pEZH2)and synergistic treatment of prostate cancer.The pEZH2/Pt(II)could be effectively triggered to unpack/release from NPCSPt/pEZH2 in a chain-shattering manner in cancer cells.The EZH2 gene disruption efficiency could be achieved up to 32.2%of PC-3 cells in vitro and 21.3%of tumor tissues in vivo,leading to effective suppression of EZH2 protein expression.Moreover,significant H3K27me3 downregulation could occur after EZH2 suppression,resulting in a more permissive chromatin structure that increases the accessibility of released Pt(II)to nuclear DNA for enhanced apoptosis.Taken together,substantial proliferation inhibition of prostate cancer cells and further 85.4%growth repression against subcutaneous xenograft tumor could be achieved.This chain-shattering Pt(IV)-backboned polymeric nanoplatform system not only provides a prospective nanocarrier for CRISPR/Cas9 system delivery,but also broadens the potential of combining gene editing-chemo synergistic cancer therapy.
基金supported by the National Key Research and Development Program of China(2016YFA0203600)the National Natural Science Foundation of China(51503180,5161101036)+1 种基金“Thousand Talents Program”for Distinguished Young Scholars(588020*G81501/048)Fundamental Research Funds for the Central Universities(520002*172210161)
文摘Platinum(Pt) based drugs, such as cisplatin, are widely used as anti-cancer agents, but their severe adverse reactions and resistance of cancer patients have limited their board clinical use. For the last few decades, Pt(Ⅱ) compounds, Pt(Ⅳ) prodrugs as well as smart drug delivery systems have been developed to overcome these problems. However, most conventional strategies rely on the similar anti-cancer mechanism with cisplatin and consequently only achieve limited success. Recently, Pt nanocrystals/nanoclusters(Pt NCs), with a brand new anti-cancer mechanism, have shown a promising potential in targeted cancer therapy, especially in Pt resistance circumvention. This review is helpful to understand the research strategies of Pt drugs, particularly, the recent developments and medical applications of Pt NCs.
基金support of the National Basic Research Program of China(Nos.2017YFA0205301 and 2015CB931802)the National Natural Scientific Foundation of China(Nos.81903169,81803094,81602184,81822024,and 81571729)+5 种基金Shanghai Municipal Commission of Economy and Information Technology Fund(No.XC-ZXSJ-02-2016-05)the Medical Engineering Cross Project of Shanghai Jiao Tong university(Nos.YG2016ZD10 and YG2017Z D05)the Project of Thousand Youth Talents from China,and the National Key Research and Development Program of China(No.2017YFC1200904)the financial support of Shanghai Sailing Program(No.19YF1422300)Sponsor from Startup Fund for Yongman Research at SJTU(No.18X100040044)Shanghai Engineering Research Center for Intelligent Diagnosis and Treatment Instrument(No.15DZ2252000)are also acknowledged.
文摘Distinctively different metabolism between tumor cells and normal cells endows tumor tissues unique microenvironment.In this regard,we have successfully prepared a sequential catalytic platform based on Au/Pt star for tumor theragnostic.The multifunctional probes consisted of a gold/platinum star-shaped core(Au/Pt star)conjugated with a GSH-sensitive disulfide bond(S–S),a targeting ligand(rHSA-FA),a near-infrared fluorophore(IR780)and glucose oxidase(GOx).When systemically administered in a xenografted murine model,the probes specifically targeted the tumor sites.As the disulfide linker was cleaved by intracellular GSH,the IR780 molecules could be released for photo-thermal therapy&photodynamic therapy(PTT&PDT)and imaging.Subsequently,the Pt nanolayer of the Au/Pt star and the GOx formed a sequential catalytic system:GOx effectively catalyzed intracellular glucose by consuming oxygen to generate H2O2 and enhance the local acidity,and the Pt layer exhibited peroxidase-like property to catalyze H2O2 producing toxic·OH for tumor oxidative damage.Here we demonstrated that our probes simultaneously possessed a GSH-sensitive release,real-time imaging ability,and synergetic cancer starving-like therapy/enzyme oxidative therapy/PTT/PDT features,which provides a potential strategy for effective tumor theragnostic.
