RNAs are involved in the crucial processes of disease progression and have emerged as powerful therapeutic targets and diagnostic biomarkers.However,efficient delivery of therapeutic RNA to the targeted location and p...RNAs are involved in the crucial processes of disease progression and have emerged as powerful therapeutic targets and diagnostic biomarkers.However,efficient delivery of therapeutic RNA to the targeted location and precise detection of RNA markers remains challenging.Recently,more and more attention has been paid to applying nucleic acid nanoassemblies in diagnosing and treating.Due to the flexibility and deformability of nucleic acids,the nanoassemblies could be fabricated with different shapes and structures.With hybridization,nucleic acid nanoassemblies,including DNA and RNA nanostructures,can be applied to enhance RNA therapeutics and diagnosis.This review briefly introduces the construction and properties of different nucleic acid nanoassemblies and their applications for RNA therapy and diagnosis and makes further prospects for their development.展开更多
The cancer stem cell(CSC)theory is gaining increasing attention from researchers and has become an important focus of cancer research.According to the theory,a minority population of cancer cells is capable of self-re...The cancer stem cell(CSC)theory is gaining increasing attention from researchers and has become an important focus of cancer research.According to the theory,a minority population of cancer cells is capable of self-renewal and generation of differentiated progeny,termed cancer stem cells(CSCs).Understanding the properties and characteristics of CSCs is key to future study on cancer research,such as the isolation and identification of CSCs,the cancer diagnosis,and the cancer therapy.Standard oncology treatments,such as chemotherapy,radiotherapy and surgical resection,can only shrink the bulk tumor and the tumor tends to relapse.Thus,therapeutic strategies that focus on targeting CSCs and their microenvironmental niche address the ineffec-tiveness of traditional cancer therapies to eradicate the CSCs that otherwise result in therapy resistance.The combined use of traditional therapies with targeted CSC-specific agents may target the whole cancer and offer a promising strategy for lasting treatment and even cure.展开更多
Interference with calcium homeostasis provokes tumor cell death and immune response,providing a novel direction for tumor immunotherapy as a promising cancer treatment strategy.Nevertheless,most reported Ca^(2+)-overl...Interference with calcium homeostasis provokes tumor cell death and immune response,providing a novel direction for tumor immunotherapy as a promising cancer treatment strategy.Nevertheless,most reported Ca^(2+)-overloaded nanoinducers encounter challenges such as intricate preparation procedures,safety concerns arising from inorganic material input,and limited anti-tumor efficiency.Herein,we synthesized a biocompatible and pH-sensitive Ca-doped cyclodextrin metal-organic framework(Ca/K-MOF)as a carrier,which was then loaded with photosensitizer hypericin(HY)via a simple one-pot synthesis to form HY@Ca/K-MOF.To enhance the stability both in vitro and in vivo,we coated HY@Ca/K-MOF with a hydrophilic layer of ^(PEG)(^(PEG)HY@Ca/K-MOF).When exposed to 590 nm photoirradiation,^(PEG)HY@Ca/K-MOF,with its pH-responsive dissociation,the Ca^(2+)and HY mediators released at the tumor site share the responsibility of triggering intracellular Ca^(2+)disturbances,which amplified the production of reactive oxygen species(ROS)and led to mitochondrial calcium overload through modulating mitochondrial MICU1 function.Under photocontrol,this interplay between ROS generation and mitochondrial calcium overload created a bidirectional amplification effect,where each process reinforced the other,subsequently eliciting a pyroptosis-evoked immune response.Significantly,this newly constructed delivery platform effectively suppressed both primary and distant tumors without the need for additional immunological interventions.In summary,this Ca^(2+)-doped MOF-based nanomaterial provides a promising approach for efficient tumor photo-controlled mitochondrial Ca^(2+)overload-pyroptosis immunotherapy.展开更多
基金supported by the National Science Foundation of China(No.82003689,to Mengnan Zhao,China)the Outstanding Young Scientific Talent Foundation of Sichuan Province(No.2022JDJQ0052,to Sanjun Shi,China)+3 种基金the China Postdoctoral Science Foundation(No.2021M690489,to Mengnan Zhao,China)the Project of High-Level Talents in Sichuan Province(No.003113014003,to Sanjun Shi,China)the International Postdoctoral Exchange Fellowship Program(No.YJ20200040,to Mengnan Zhao,China)the Xinglin Scholar Research Promotion Project of Chengdu University of Traditional Chinese Medicine(No.BSH2020006,to Mengnan Zhao,China).
文摘RNAs are involved in the crucial processes of disease progression and have emerged as powerful therapeutic targets and diagnostic biomarkers.However,efficient delivery of therapeutic RNA to the targeted location and precise detection of RNA markers remains challenging.Recently,more and more attention has been paid to applying nucleic acid nanoassemblies in diagnosing and treating.Due to the flexibility and deformability of nucleic acids,the nanoassemblies could be fabricated with different shapes and structures.With hybridization,nucleic acid nanoassemblies,including DNA and RNA nanostructures,can be applied to enhance RNA therapeutics and diagnosis.This review briefly introduces the construction and properties of different nucleic acid nanoassemblies and their applications for RNA therapy and diagnosis and makes further prospects for their development.
文摘The cancer stem cell(CSC)theory is gaining increasing attention from researchers and has become an important focus of cancer research.According to the theory,a minority population of cancer cells is capable of self-renewal and generation of differentiated progeny,termed cancer stem cells(CSCs).Understanding the properties and characteristics of CSCs is key to future study on cancer research,such as the isolation and identification of CSCs,the cancer diagnosis,and the cancer therapy.Standard oncology treatments,such as chemotherapy,radiotherapy and surgical resection,can only shrink the bulk tumor and the tumor tends to relapse.Thus,therapeutic strategies that focus on targeting CSCs and their microenvironmental niche address the ineffec-tiveness of traditional cancer therapies to eradicate the CSCs that otherwise result in therapy resistance.The combined use of traditional therapies with targeted CSC-specific agents may target the whole cancer and offer a promising strategy for lasting treatment and even cure.
基金supported by the Centrally Guided Local Science and Technology Development Project(No.2024ZYD0043,China)the Chongqing Natural Science Foundation(No.CSTB2022NSCQ-MSX0350,China)+2 种基金the National Natural Science Foundation of China(No.82405161)the Sichuan Province Joint Fund for Science and Education(No.2024NSFSC2124,China)the Xinglin Scholar Research Promotion Project of Chengdu University of TCM(Nos.BSZ2024002 and QJRC2024018,China).
文摘Interference with calcium homeostasis provokes tumor cell death and immune response,providing a novel direction for tumor immunotherapy as a promising cancer treatment strategy.Nevertheless,most reported Ca^(2+)-overloaded nanoinducers encounter challenges such as intricate preparation procedures,safety concerns arising from inorganic material input,and limited anti-tumor efficiency.Herein,we synthesized a biocompatible and pH-sensitive Ca-doped cyclodextrin metal-organic framework(Ca/K-MOF)as a carrier,which was then loaded with photosensitizer hypericin(HY)via a simple one-pot synthesis to form HY@Ca/K-MOF.To enhance the stability both in vitro and in vivo,we coated HY@Ca/K-MOF with a hydrophilic layer of ^(PEG)(^(PEG)HY@Ca/K-MOF).When exposed to 590 nm photoirradiation,^(PEG)HY@Ca/K-MOF,with its pH-responsive dissociation,the Ca^(2+)and HY mediators released at the tumor site share the responsibility of triggering intracellular Ca^(2+)disturbances,which amplified the production of reactive oxygen species(ROS)and led to mitochondrial calcium overload through modulating mitochondrial MICU1 function.Under photocontrol,this interplay between ROS generation and mitochondrial calcium overload created a bidirectional amplification effect,where each process reinforced the other,subsequently eliciting a pyroptosis-evoked immune response.Significantly,this newly constructed delivery platform effectively suppressed both primary and distant tumors without the need for additional immunological interventions.In summary,this Ca^(2+)-doped MOF-based nanomaterial provides a promising approach for efficient tumor photo-controlled mitochondrial Ca^(2+)overload-pyroptosis immunotherapy.
