Combining existing drug therapy is essential in developing new therapeutic agents in disease prevention and treatment.In preclinical investigations,combined effect of certain known drugs has been well established in t...Combining existing drug therapy is essential in developing new therapeutic agents in disease prevention and treatment.In preclinical investigations,combined effect of certain known drugs has been well established in treating extensive human diseases.Attributed to synergistic effects by targeting various disease pathways and advantages,such as reduced administration dose,decreased toxicity,and alleviated drug resistance,combinatorial treatment is now being pursued by delivering therapeutic agents to combat major clinical illnesses,such as cancer,atherosclerosis,pulmonary hypertension,myocarditis,rheumatoid arthritis,inflammatory bowel disease,metabolic disorders and neurodegenerative diseases.Combinatorial therapy involves combining or co-delivering two or more drugs for treating a specific disease.Nanoparticle(NP)-mediated drug delivery systems,i.e.,liposomal NPs,polymeric NPs and nanocrystals,are of great interest in combinatorial therapy for a wide range of disorders due to targeted drug delivery,extended drug release,and higher drug stability to avoid rapid clearance at infected areas.This review summarizes various targets of diseases,preclinical or clinically approved drug combinations and the development of multifunctional NPs for combining therapy and emphasizes combinatorial therapeutic strategies based on drug delivery for treating severe clinical diseases.Ultimately,we discuss the challenging of developing NP-codelivery and translation and provide potential approaches to address the limitations.This review offers a comprehensive overview for recent cutting-edge and challenging in developing NP-mediated combination therapy for human diseases.展开更多
Smart drug delivery nanosystem is significant for tumor treatments due to its possibility of temporally,spatially,and dose-controlled release.However,the therapeutic efficacy of drug delivery nanosystem is often compr...Smart drug delivery nanosystem is significant for tumor treatments due to its possibility of temporally,spatially,and dose-controlled release.However,the therapeutic efficacy of drug delivery nanosystem is often compromised in cancer treatment as the enrichment of therapeutic agents in the reticuloendothelial system.Herein,doxorubicin(DOX)loaded biomimetic drug delivery nanosystem with macrophage cell membrane(MCM)camouflaged,MnFe_(2)O_(4)-DOX-MCM nanocube(NC),is developed for cancer treatment with tumor targeting,pH-stimuli drug release,and chemo-photothermal therapeutic effects.The nanosystem shows the capability of immune escape and enhanced cellular uptake of cancer cells due to the MCM decoration.Acid-labile bond between the MnFe2O4 NCs and DOX remains stable at physiological condition and release drugs immediately in response to the endo-/lysosome pH stimuli.Meanwhile,the photothermal effect of the nanosystem destroys tumor tissue,which further promotes chemotherapeutic efficacy.In vivo results demonstrate the tumor homing ability and produce a notable synergistic therapeutic effect of the NCs.Thus,biomimetic pH-responsive drug delivery nanosystem,MnFe_(2)O_(4)-DOX-MCM NCs,is an effective nanoplatform,which might be potential application for cancer synergistic treatment.展开更多
Recently, magnetic nanopartides （NPs） have been extensively used in food industry and biomedical treatments. However, the biocompatibility mechanism on expression proteomics, before consideration of magnetic NPs for...Recently, magnetic nanopartides （NPs） have been extensively used in food industry and biomedical treatments. However, the biocompatibility mechanism on expression proteomics, before consideration of magnetic NPs for clinical application, has not yet been fully elucidated. Therefore, this study was undertaken to identify potential biomarkers of metal ion signaling proteins in human cervical cancer cell line （HeLa） cells. Here, we report the in vitro investigations of the cell cycle response and significant changes in protein abundance of HeLa cells when exposed to self-tailored hydrophilic Fe2C NPs. The comparative proteomic approach based on 180 labeling coupled with high performance liquid chromatography/ electrospray ionization with ion trap mass analyzer （HPLC/ESI-Orbitrap） was applied, and 394 proteins were identified. There were 46 significantly differentiated proteins based on the specific metal ion signaling response. Among them, 60S ribosomal protein L37a, serine/arginine-rich splicing factor 7, calmodulin, and calumenin were downregulated, whereas transketolase was overexpressed. Functional interaction network of Fe2C-regulated proteins was successfully created by the STRING algorithm to show the strong interactions between proteins. This work will not only help to understand the molecular mechanism of metal ion signaling proteins that can potentially be used to develop therapeutic protocols for diagnosis of diseases but also give direction for tailoring biocompatible magnetic NPs.展开更多
基金supported by the National Natural Science Foundation of China(Nos.81872823,82073782 and 82241002)the Shanghai Science and Technology Committee(No.19430741500)the Key Laboratory of Modern Chinese Medicine Preparation of Ministry of Education of Jiangxi University of Traditional Chinese Medicine(days-202103).
文摘Combining existing drug therapy is essential in developing new therapeutic agents in disease prevention and treatment.In preclinical investigations,combined effect of certain known drugs has been well established in treating extensive human diseases.Attributed to synergistic effects by targeting various disease pathways and advantages,such as reduced administration dose,decreased toxicity,and alleviated drug resistance,combinatorial treatment is now being pursued by delivering therapeutic agents to combat major clinical illnesses,such as cancer,atherosclerosis,pulmonary hypertension,myocarditis,rheumatoid arthritis,inflammatory bowel disease,metabolic disorders and neurodegenerative diseases.Combinatorial therapy involves combining or co-delivering two or more drugs for treating a specific disease.Nanoparticle(NP)-mediated drug delivery systems,i.e.,liposomal NPs,polymeric NPs and nanocrystals,are of great interest in combinatorial therapy for a wide range of disorders due to targeted drug delivery,extended drug release,and higher drug stability to avoid rapid clearance at infected areas.This review summarizes various targets of diseases,preclinical or clinically approved drug combinations and the development of multifunctional NPs for combining therapy and emphasizes combinatorial therapeutic strategies based on drug delivery for treating severe clinical diseases.Ultimately,we discuss the challenging of developing NP-codelivery and translation and provide potential approaches to address the limitations.This review offers a comprehensive overview for recent cutting-edge and challenging in developing NP-mediated combination therapy for human diseases.
基金supported by the National Natural Science Foundation of China (51602285, 51590882, 51631001, 51672010 and 81421004)the National Key R&D Program of China (2017YFA0206301)the Key Laboratory of Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and technology, Chinese Academy of Sciences (NSKF201607)
基金This work was financially supported by the National Natural Science Foundation of China(Nos.52027801,51631001,and 52002402)the National Key R&D Program of China(No.2017YFA0206301)+1 种基金the Natural Science Foundation of Beijing Municipality(No.2191001),and the China-German Collaboration Project(No.M-0199)the Natural Science Foundation of Jiangsu Province(No.BK20200574)。
文摘Smart drug delivery nanosystem is significant for tumor treatments due to its possibility of temporally,spatially,and dose-controlled release.However,the therapeutic efficacy of drug delivery nanosystem is often compromised in cancer treatment as the enrichment of therapeutic agents in the reticuloendothelial system.Herein,doxorubicin(DOX)loaded biomimetic drug delivery nanosystem with macrophage cell membrane(MCM)camouflaged,MnFe_(2)O_(4)-DOX-MCM nanocube(NC),is developed for cancer treatment with tumor targeting,pH-stimuli drug release,and chemo-photothermal therapeutic effects.The nanosystem shows the capability of immune escape and enhanced cellular uptake of cancer cells due to the MCM decoration.Acid-labile bond between the MnFe2O4 NCs and DOX remains stable at physiological condition and release drugs immediately in response to the endo-/lysosome pH stimuli.Meanwhile,the photothermal effect of the nanosystem destroys tumor tissue,which further promotes chemotherapeutic efficacy.In vivo results demonstrate the tumor homing ability and produce a notable synergistic therapeutic effect of the NCs.Thus,biomimetic pH-responsive drug delivery nanosystem,MnFe_(2)O_(4)-DOX-MCM NCs,is an effective nanoplatform,which might be potential application for cancer synergistic treatment.
文摘Recently, magnetic nanopartides （NPs） have been extensively used in food industry and biomedical treatments. However, the biocompatibility mechanism on expression proteomics, before consideration of magnetic NPs for clinical application, has not yet been fully elucidated. Therefore, this study was undertaken to identify potential biomarkers of metal ion signaling proteins in human cervical cancer cell line （HeLa） cells. Here, we report the in vitro investigations of the cell cycle response and significant changes in protein abundance of HeLa cells when exposed to self-tailored hydrophilic Fe2C NPs. The comparative proteomic approach based on 180 labeling coupled with high performance liquid chromatography/ electrospray ionization with ion trap mass analyzer （HPLC/ESI-Orbitrap） was applied, and 394 proteins were identified. There were 46 significantly differentiated proteins based on the specific metal ion signaling response. Among them, 60S ribosomal protein L37a, serine/arginine-rich splicing factor 7, calmodulin, and calumenin were downregulated, whereas transketolase was overexpressed. Functional interaction network of Fe2C-regulated proteins was successfully created by the STRING algorithm to show the strong interactions between proteins. This work will not only help to understand the molecular mechanism of metal ion signaling proteins that can potentially be used to develop therapeutic protocols for diagnosis of diseases but also give direction for tailoring biocompatible magnetic NPs.
