Gemcitabine has been extensively applied in treating various solid tumors. Nonetheless,the clinical performance of gemcitabine is severely restricted by its unsatisfactory pharmacokinetic parameters and easy deactivat...Gemcitabine has been extensively applied in treating various solid tumors. Nonetheless,the clinical performance of gemcitabine is severely restricted by its unsatisfactory pharmacokinetic parameters and easy deactivation mainly because of its rapid deamination, deficiencies in deoxycytidine kinase (DCK), and alterations in nucleoside transporter. On this account, repeated injections with a high concentration of gemcitabine are adopted, leading to severe systemic toxicity to healthy cells. Accordingly, it is highly crucial to fabricate efficient gemcitabine delivery systems to obtain improved therapeutic efficacy of gemcitabine. A large number of gemcitabine pro-drugs were synthesized by chemical modification of gemcitabine to improve its biostability and bioavailability. Besides,gemcitabine-loaded nano-drugs were prepared to improve the delivery efficiency. In this review article, we introduced different strategies for improving the therapeutic performance of gemcitabine by the fabrication of pro-drugs and nano-drugs. We hope this review will provide new insight into the rational design of gemcitabine-based delivery strategies for enhanced cancer therapy.展开更多
Bone tumour is one of most common primary cancer which exhibits cancerous osteoblastic differentiation and malignant osteoid in patients.At present,chemotherapy(pre-and post-operative)is used as a standard treatment p...Bone tumour is one of most common primary cancer which exhibits cancerous osteoblastic differentiation and malignant osteoid in patients.At present,chemotherapy(pre-and post-operative)is used as a standard treatment protocol for bone tumour.However,drugs used in the treatment of bone tumour induce high toxicity to normal tissues including anaemia,neutropenia,thrombocytopenia,and heart damage which further reduce the survival rate of patients.Therefore,there is an urgent need to develop a new therapeutic approach for the treatment such that it induce maximum cell killing effect in tumor cells while sparing the healthy bone cells.In this article,some new perspectives were provided on the development of bone-targeted nano-drug carriers for bone cancer treatment.We hope such discussions wouldencourage more detailed and careful studies to support product development of bone-targeted drug carriers for bone cancer treatment.展开更多
Nano materials is a new type of drug carriers with very promising application. In recent years, great progress was achieved in making drugs own the characteristics of targeted and con-trolled release via nanotechnolog...Nano materials is a new type of drug carriers with very promising application. In recent years, great progress was achieved in making drugs own the characteristics of targeted and con-trolled release via nanotechnologies. This paper addressed the capability of nano drugs on tar-geting to cells, penetrating through epicyte, controlled release and the security issues re-sulting from its using. We gave the prospect of nano drugs in biology and medicine applying.展开更多
In recent years,owing to the miniaturization of the fluidic environment,microfluidic technology offers unique opportunities for the implementation of nano drug delivery systems(NDDSs)production processes.Compared with...In recent years,owing to the miniaturization of the fluidic environment,microfluidic technology offers unique opportunities for the implementation of nano drug delivery systems(NDDSs)production processes.Compared with traditional methods,microfluidics improves the controllability and uniformity of NDDSs.The fast mixing and laminar flow properties achieved in the microchannels can tune the physicochemical properties of NDDSs,including particle size,distribution and morphology,resulting in narrow particle size distribution and high drug-loading capacity.The success of lipid nanoparticles encapsulated mRNA vaccines against coronavirus disease 2019 by microfluidics also confirmed its feasibility for scaling up the preparation of NDDSs via parallelization or numbering-up.In this review,we provide a comprehensive summary of microfluidics-based NDDSs,including the fundamentals of microfluidics,microfluidic synthesis of NDDSs,and their industrialization.The challenges of microfluidicsbased NDDSs in the current status and the prospects for future development are also discussed.We believe that this review will provide good guidance for microfluidics-based NDDSs.展开更多
As one of the most important components of caveolae,caveolin-1 is involved in caveolaemediated endocytosis and transcytosis pathways,and also plays a role in regulating the cell membrane cholesterol homeostasis and me...As one of the most important components of caveolae,caveolin-1 is involved in caveolaemediated endocytosis and transcytosis pathways,and also plays a role in regulating the cell membrane cholesterol homeostasis and mediating signal transduction.In recent years,the relationship between the expression level of caveolin-1 in the tumor microenvironment and the prognostic effect of tumor treatment and drug treatment resistance has also been widely explored.In addition,the interplay between caveolin-1 and nano-drugs is bidirectional.Caveolin-1 could determine the intracellular biofate of specifc nano-drugs,preventing from lysosomal degradation,and facilitate them penetrate into deeper site of tumors by transcytosis;while some nanocarriers could also affect caveolin-1 levels in tumor cells,thereby changing certain biophysical function of cells.This article reviews the role of caveolin-1 in tumor prognosis,chemotherapeutic drug resistance,antibody drug sensitivity,and nano-drug delivery,providing a reference for the further application of caveolin-1 in nano-drug delivery systems.展开更多
Due to the special physiological and pathological characteristics of gliomas,most therapeutic drugs are prevented from entering the brain.To improve the poor prognosis of existing therapies,researchers have been conti...Due to the special physiological and pathological characteristics of gliomas,most therapeutic drugs are prevented from entering the brain.To improve the poor prognosis of existing therapies,researchers have been continuously developing non-invasive methods to overcome barriers to gliomas therapy.Although these strategies can be used clinically to overcome the blood-brain barrier(BBB),the accurate delivery of drugs to the glioma lesions cannot be ensured.Nano-drug delivery systems(NDDS)have been widely used for precise drug delivery.In recent years,researchers have gathered their wisdom to overcome barriers,so many well-designed NDDS have performed prominently in preclinical studies.These meticulous designs mainly include cascade passing through BBB and targeting to glioma lesions,drug release in response to the glioma microenvironment,biomimetic delivery systems based on endogenous cells/extracellular vesicles/protein,and carriers created according to the active ingredients of traditional Chinese medicines.We reviewed these well-designed NDDS in detail.Furthermore,we discussed the current ongoing and completed clinical trials of NDDS for gliomas therapy,and analyzed the challenges and trends faced by clinical translation of these well-designed NDDS.展开更多
基金supported by the Natural Science Foundation of China (Grant Nos. 52022090, 22005265, 82070739, 81870641)National Key R&D Program of China (Grant No. 2018YFC1106104)+3 种基金Key Research and Development Program of Zhejiang Province (Grant No. 2020C03035)Zhejiang Provincial Natural Science Foundation of China (Grant No. LQ20E030011)Zhejiang Medical Health Science and Technology Program (Grant No. 2021RC061)Zhejiang Provincial Ten Thousand Talents Program (2018R52001)。
文摘Gemcitabine has been extensively applied in treating various solid tumors. Nonetheless,the clinical performance of gemcitabine is severely restricted by its unsatisfactory pharmacokinetic parameters and easy deactivation mainly because of its rapid deamination, deficiencies in deoxycytidine kinase (DCK), and alterations in nucleoside transporter. On this account, repeated injections with a high concentration of gemcitabine are adopted, leading to severe systemic toxicity to healthy cells. Accordingly, it is highly crucial to fabricate efficient gemcitabine delivery systems to obtain improved therapeutic efficacy of gemcitabine. A large number of gemcitabine pro-drugs were synthesized by chemical modification of gemcitabine to improve its biostability and bioavailability. Besides,gemcitabine-loaded nano-drugs were prepared to improve the delivery efficiency. In this review article, we introduced different strategies for improving the therapeutic performance of gemcitabine by the fabrication of pro-drugs and nano-drugs. We hope this review will provide new insight into the rational design of gemcitabine-based delivery strategies for enhanced cancer therapy.
基金The project supported by National Natural Science Foundation of China(81300964)the China Postdoctoral Science Foundation(2013M531611,2014T70648)
文摘Bone tumour is one of most common primary cancer which exhibits cancerous osteoblastic differentiation and malignant osteoid in patients.At present,chemotherapy(pre-and post-operative)is used as a standard treatment protocol for bone tumour.However,drugs used in the treatment of bone tumour induce high toxicity to normal tissues including anaemia,neutropenia,thrombocytopenia,and heart damage which further reduce the survival rate of patients.Therefore,there is an urgent need to develop a new therapeutic approach for the treatment such that it induce maximum cell killing effect in tumor cells while sparing the healthy bone cells.In this article,some new perspectives were provided on the development of bone-targeted nano-drug carriers for bone cancer treatment.We hope such discussions wouldencourage more detailed and careful studies to support product development of bone-targeted drug carriers for bone cancer treatment.
文摘Nano materials is a new type of drug carriers with very promising application. In recent years, great progress was achieved in making drugs own the characteristics of targeted and con-trolled release via nanotechnologies. This paper addressed the capability of nano drugs on tar-geting to cells, penetrating through epicyte, controlled release and the security issues re-sulting from its using. We gave the prospect of nano drugs in biology and medicine applying.
基金supported by the projects of National Natural Science Foundation of China(No.82073784,China)Jilin Province Science and Technology Development Program(No.20200801012GH,China)Industrial Technology Research and Development Projects from the Development and Reform Commission of Jilin Province Major Science and Technology Special Projects(20200504005YY,China)。
文摘In recent years,owing to the miniaturization of the fluidic environment,microfluidic technology offers unique opportunities for the implementation of nano drug delivery systems(NDDSs)production processes.Compared with traditional methods,microfluidics improves the controllability and uniformity of NDDSs.The fast mixing and laminar flow properties achieved in the microchannels can tune the physicochemical properties of NDDSs,including particle size,distribution and morphology,resulting in narrow particle size distribution and high drug-loading capacity.The success of lipid nanoparticles encapsulated mRNA vaccines against coronavirus disease 2019 by microfluidics also confirmed its feasibility for scaling up the preparation of NDDSs via parallelization or numbering-up.In this review,we provide a comprehensive summary of microfluidics-based NDDSs,including the fundamentals of microfluidics,microfluidic synthesis of NDDSs,and their industrialization.The challenges of microfluidicsbased NDDSs in the current status and the prospects for future development are also discussed.We believe that this review will provide good guidance for microfluidics-based NDDSs.
文摘As one of the most important components of caveolae,caveolin-1 is involved in caveolaemediated endocytosis and transcytosis pathways,and also plays a role in regulating the cell membrane cholesterol homeostasis and mediating signal transduction.In recent years,the relationship between the expression level of caveolin-1 in the tumor microenvironment and the prognostic effect of tumor treatment and drug treatment resistance has also been widely explored.In addition,the interplay between caveolin-1 and nano-drugs is bidirectional.Caveolin-1 could determine the intracellular biofate of specifc nano-drugs,preventing from lysosomal degradation,and facilitate them penetrate into deeper site of tumors by transcytosis;while some nanocarriers could also affect caveolin-1 levels in tumor cells,thereby changing certain biophysical function of cells.This article reviews the role of caveolin-1 in tumor prognosis,chemotherapeutic drug resistance,antibody drug sensitivity,and nano-drug delivery,providing a reference for the further application of caveolin-1 in nano-drug delivery systems.
基金financial support from National Natural Science Foundation of China(Nos.81903557 and 82074024)Natural Science Foundation of Jiangsu Province(No.BK20190802,China)+3 种基金Natural Science Foundation Youth Project of Nanjing University of Chinese Medicine(No.NZY81903557,China)the Open Project of Chinese Materia Medica First-Class Discipline of Nanjing University of Chinese Medicine(No.2020YLXK019,China)the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(No.19KJB350003,China)College Students’Innovative Entrepreneurial Training Plan Program of Nanjing University of Chinese Medicine(No.202010315XJ040,China)。
文摘Due to the special physiological and pathological characteristics of gliomas,most therapeutic drugs are prevented from entering the brain.To improve the poor prognosis of existing therapies,researchers have been continuously developing non-invasive methods to overcome barriers to gliomas therapy.Although these strategies can be used clinically to overcome the blood-brain barrier(BBB),the accurate delivery of drugs to the glioma lesions cannot be ensured.Nano-drug delivery systems(NDDS)have been widely used for precise drug delivery.In recent years,researchers have gathered their wisdom to overcome barriers,so many well-designed NDDS have performed prominently in preclinical studies.These meticulous designs mainly include cascade passing through BBB and targeting to glioma lesions,drug release in response to the glioma microenvironment,biomimetic delivery systems based on endogenous cells/extracellular vesicles/protein,and carriers created according to the active ingredients of traditional Chinese medicines.We reviewed these well-designed NDDS in detail.Furthermore,we discussed the current ongoing and completed clinical trials of NDDS for gliomas therapy,and analyzed the challenges and trends faced by clinical translation of these well-designed NDDS.