分子检测技术的不断进步极大地推动了肺癌精准医学的发展,但是肿瘤的异质性与肿瘤的转移、复发和耐药密切相关,并且具有同一基因突变的不同肺癌患者采用不同的治疗策略会呈现出一定的疗效差异,因此现代精准医学的发展亟需通过个性化的...分子检测技术的不断进步极大地推动了肺癌精准医学的发展,但是肿瘤的异质性与肿瘤的转移、复发和耐药密切相关,并且具有同一基因突变的不同肺癌患者采用不同的治疗策略会呈现出一定的疗效差异,因此现代精准医学的发展亟需通过个性化的肿瘤模型来精准制定个性化的治疗策略。肺癌类器官(lung cancer organoid,LCO)能够高度模拟肿瘤在体内的生物学特征,促进抗体药物偶联物等创新药物在肺癌精准医学的应用。随着LCO与肿瘤微环境共培养模型和微流控芯片等组织工程技术的发展,LCO可以更好地保留肿瘤组织的生物学特征和功能,进一步提高高通量和自动化药物敏感性实验。本文结合了最新的LCO研究进展,总结了LCO在肺癌精准医学中的应用进展与挑战。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
Understanding the interactions between inorganic nanomaterials and biological species is an important topic for surface and environmental chemistry. In this work, we systematically studied the oocysts of Cryptosporidi...Understanding the interactions between inorganic nanomaterials and biological species is an important topic for surface and environmental chemistry. In this work, we systematically studied the oocysts of Cryptosporidium pa r v u m as a model protozoan parasite and its interaction with gold nanoparticles (AuNPs) and graphene oxide (GO). The as-prepared citrate-capped AuNPs adsorb strongly on the oocysts leading to a vivid color change. The adsorption of the AuNPs was confirmed by transmission electron microscopy. Heat treatment fully inhibited the color change, indicating a large change of surface chemistry of the oocysts that can be probed by the AuNPs. Adding proteases such as trypsin and proteinase K partially inhibited the color change. DNA-capped AuNPs, on the other hand, could not be adsorbed by the oocysts. GO was found to wrap around the oocysts forming a conformal shell reflecting the shape of the oocysts. Both citratecapped AuNPs and GO compromised the membrane integrity of the oocysts as indicated by the propidium iodide staining experiment, and they may be potentially used for inactivating the oocysts. This is the first example of using nanomaterials to probe the surface of the oocysts, and it suggests the possibility of using such organisms to template the assembly of nanomaterials.展开更多
文摘分子检测技术的不断进步极大地推动了肺癌精准医学的发展,但是肿瘤的异质性与肿瘤的转移、复发和耐药密切相关,并且具有同一基因突变的不同肺癌患者采用不同的治疗策略会呈现出一定的疗效差异,因此现代精准医学的发展亟需通过个性化的肿瘤模型来精准制定个性化的治疗策略。肺癌类器官(lung cancer organoid,LCO)能够高度模拟肿瘤在体内的生物学特征,促进抗体药物偶联物等创新药物在肺癌精准医学的应用。随着LCO与肿瘤微环境共培养模型和微流控芯片等组织工程技术的发展,LCO可以更好地保留肿瘤组织的生物学特征和功能,进一步提高高通量和自动化药物敏感性实验。本文结合了最新的LCO研究进展,总结了LCO在肺癌精准医学中的应用进展与挑战。
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.
文摘Understanding the interactions between inorganic nanomaterials and biological species is an important topic for surface and environmental chemistry. In this work, we systematically studied the oocysts of Cryptosporidium pa r v u m as a model protozoan parasite and its interaction with gold nanoparticles (AuNPs) and graphene oxide (GO). The as-prepared citrate-capped AuNPs adsorb strongly on the oocysts leading to a vivid color change. The adsorption of the AuNPs was confirmed by transmission electron microscopy. Heat treatment fully inhibited the color change, indicating a large change of surface chemistry of the oocysts that can be probed by the AuNPs. Adding proteases such as trypsin and proteinase K partially inhibited the color change. DNA-capped AuNPs, on the other hand, could not be adsorbed by the oocysts. GO was found to wrap around the oocysts forming a conformal shell reflecting the shape of the oocysts. Both citratecapped AuNPs and GO compromised the membrane integrity of the oocysts as indicated by the propidium iodide staining experiment, and they may be potentially used for inactivating the oocysts. This is the first example of using nanomaterials to probe the surface of the oocysts, and it suggests the possibility of using such organisms to template the assembly of nanomaterials.
