The five-year survival rate for pancreatic cancer is less than 5%. However, the current clinical multimodal therapy combined with first-line chemotherapy drugs only increases the patient’s median survival from 5.0 mo...The five-year survival rate for pancreatic cancer is less than 5%. However, the current clinical multimodal therapy combined with first-line chemotherapy drugs only increases the patient’s median survival from 5.0 months to 7.2 months. Consequently, a new strategy of cancer treatments is urgently needed to overcome this high-fatality disease. Through a series of biometric analyses, we found that KRAS is highly expressed in the tumor of pancreatic cancer patients, and this high expression is closely related to the poor prognosis of patients. It shows that inhibiting the expression of KRAS has great potential in gene therapy for pancreatic cancer. Given those above, we have exploited the possibility of targeted delivery of KRAS shRNA with the intelligent and bio-responsive nanomedicine to detect the special oxidative stress microenvironment of cancer cells and realize efficient cancer theranostics. Our observations demonstrate that by designing the smart self-assembled nanocapsules of melanin with fluorescent nanoclusters we can readily achieve the bio-recognition and bioimaging of cancer cells in biological solution or serum.The self-assembled nanocapsules can make a significant bio-response to the oxidative stress microenvironment of cancer cells and generate fluorescent zinc oxide Nanoclusters in situ for targeted cell bioimaging. Moreover, it can also readily facilitate cancer cell suppression through the targeted delivery of KRAS shRNA and low-temperature hyperthermia. This raises the possibility to provide a promising theranostics platform and self-assembled nanomedicine for targeted cancer diagnostics and treatments through special oxidative stress-responsive effects of cancer cells.展开更多
Bacterial infection is rising as a threatening health issue.Because of the present delay in early diagnosis of bacterial diseases as well as the abuse of antibiotics,it has become a vital issue in the development of i...Bacterial infection is rising as a threatening health issue.Because of the present delay in early diagnosis of bacterial diseases as well as the abuse of antibiotics,it has become a vital issue in the development of in-time detection and therapy of bacterial infections.Herein,we designed a multifunctional nanotheranostics platform based on the unique micro-environment of bacterial infections to achieve specific bioimaging and simultaneous inactivation of the target bacteria.We showed that in bacterial infections,the metal precursors(i.e.,HAuCl_(4),FeCl_(2),and herring sperm DNA)could be readily bio-self-assembled to multifunctional nanoclusters(NCs)that exhibit luminescence,in which AuCl_(4)-was biosynthesized via reductive biomolecules such as NADPH to the fluorescent AuNCs.The DNA may assist as an encapsulation and delivery vector,and Fe^(2+)served as a fluorescence intensifier and reduced reactive oxygen species(ROS)to produce the iron oxides.While the bacteria were being visualized,the microenvironment-responsive NCs were enabled to sterilize bacteria efficiently due to electrostatic effect,cell membrane destruction,inhibition of biofilm formation,and ROS accumulation.Besides,the bio-responsive self-assembled NCs complexes contributed to accelerating bacteria-infected wound healing and showed negligible side effects in long-term toxicity tests in vivo.Also,intracellular molecules involved in microenvironmental response were investigated.The work may become an effective strategy for the detection and real-time sterilization of intractable bacterial infections.展开更多
基金supported by the National Natural Science Foundation of China (Nos. 82061148012, 82027806, 91753106)the National Key Research and Development Program of China (No. 2017YFA0205300)+1 种基金the Primary Research & Development Plan of Jiangsu Province (No. BE2019716)the program of China Scholarships Council (No. 202006090323)。
文摘The five-year survival rate for pancreatic cancer is less than 5%. However, the current clinical multimodal therapy combined with first-line chemotherapy drugs only increases the patient’s median survival from 5.0 months to 7.2 months. Consequently, a new strategy of cancer treatments is urgently needed to overcome this high-fatality disease. Through a series of biometric analyses, we found that KRAS is highly expressed in the tumor of pancreatic cancer patients, and this high expression is closely related to the poor prognosis of patients. It shows that inhibiting the expression of KRAS has great potential in gene therapy for pancreatic cancer. Given those above, we have exploited the possibility of targeted delivery of KRAS shRNA with the intelligent and bio-responsive nanomedicine to detect the special oxidative stress microenvironment of cancer cells and realize efficient cancer theranostics. Our observations demonstrate that by designing the smart self-assembled nanocapsules of melanin with fluorescent nanoclusters we can readily achieve the bio-recognition and bioimaging of cancer cells in biological solution or serum.The self-assembled nanocapsules can make a significant bio-response to the oxidative stress microenvironment of cancer cells and generate fluorescent zinc oxide Nanoclusters in situ for targeted cell bioimaging. Moreover, it can also readily facilitate cancer cell suppression through the targeted delivery of KRAS shRNA and low-temperature hyperthermia. This raises the possibility to provide a promising theranostics platform and self-assembled nanomedicine for targeted cancer diagnostics and treatments through special oxidative stress-responsive effects of cancer cells.
基金This work was supported by the National Key Research and Development Program of China(No.2017YFA0205300)the National Natural Science Foundation of China(Nos.82027806,82061148012,and 91753106)+1 种基金Primary Research&Development Plan of Jiangsu Province(No.BE2019716)the ISF-NSFC Joint Research Program(No.3258/20)to Y.W.
文摘Bacterial infection is rising as a threatening health issue.Because of the present delay in early diagnosis of bacterial diseases as well as the abuse of antibiotics,it has become a vital issue in the development of in-time detection and therapy of bacterial infections.Herein,we designed a multifunctional nanotheranostics platform based on the unique micro-environment of bacterial infections to achieve specific bioimaging and simultaneous inactivation of the target bacteria.We showed that in bacterial infections,the metal precursors(i.e.,HAuCl_(4),FeCl_(2),and herring sperm DNA)could be readily bio-self-assembled to multifunctional nanoclusters(NCs)that exhibit luminescence,in which AuCl_(4)-was biosynthesized via reductive biomolecules such as NADPH to the fluorescent AuNCs.The DNA may assist as an encapsulation and delivery vector,and Fe^(2+)served as a fluorescence intensifier and reduced reactive oxygen species(ROS)to produce the iron oxides.While the bacteria were being visualized,the microenvironment-responsive NCs were enabled to sterilize bacteria efficiently due to electrostatic effect,cell membrane destruction,inhibition of biofilm formation,and ROS accumulation.Besides,the bio-responsive self-assembled NCs complexes contributed to accelerating bacteria-infected wound healing and showed negligible side effects in long-term toxicity tests in vivo.Also,intracellular molecules involved in microenvironmental response were investigated.The work may become an effective strategy for the detection and real-time sterilization of intractable bacterial infections.
