The approved worldwide use of two messenger RNA(mRNA)vaccines(BNT162b2 and mRNA-1273)in late 2020 has proven the remarkable success of mRNA therapeutics together with lipid nanoformulation technology in protecting peo...The approved worldwide use of two messenger RNA(mRNA)vaccines(BNT162b2 and mRNA-1273)in late 2020 has proven the remarkable success of mRNA therapeutics together with lipid nanoformulation technology in protecting people against coronaviruses during COVID-19 pandemic.This unprecedented and exciting dual strategy with nanoformulations and mRNA therapeutics in play is believed to be a promising paradigm in targeted cancer immunotherapy in future.Recent advances in nanoformulation technologies play a prominent role in adapting mRNA platform in cancer treatment.In this review,we introduce the biologic principles and advancements of mRNA technology,and chemistry fundamentals of intriguing mRNA delivery nanoformulations.We discuss the latest promising nano-mRNA therapeutics for enhanced cancer immunotherapy by modulation of targeted specific subtypes of immune cells,such as dendritic cells(DCs)at peripheral lymphoid organs for initiating mRNA cancer vaccine-mediated antigen specific immunotherapy,and DCs,natural killer(NK)cells,cytotoxic T cells,or multiple immunosuppressive immune cells at tumor microenvironment(TME)for reversing immune evasion.We highlight the clinical progress of advanced nano-mRNA therapeutics in targeted cancer therapy and provide our perspectives on future directions of this transformative integrated technology toward clinical implementation.展开更多
The global incidence of oral cancer has steadily increased in recent years and is associated with high morbidity and mortality.Oral cancer is the most common cancer in the head and neck region,and is predominantly of ...The global incidence of oral cancer has steadily increased in recent years and is associated with high morbidity and mortality.Oral cancer is the most common cancer in the head and neck region,and is predominantly of epithelial origin(i.e.squamous cell carcinoma).Oral cancer treatment modalities mainly include surgery with or without radiotherapy and chemotherapy.Though proven effective,chemotherapy has significant adverse effects with possibilities of tumor resistance to anticancer drugs and recurrence.Thus,there is an imperative need to identify suitable anticancer therapies that are highly precise with minimal side effects and to make oral cancer treatment effective and safer.Among the available adjuvant therapies is curcumin,a plant polyphenol isolated from the rhizome of the turmeric plant Curcuma longa.Curcumin has been demonstrated to have antiinfectious,antioxidant,anti-inflammatory,and anticarcinogenic properties.Curcumin has poor bioavailability,which has been overcome by its various analogues and nanoformulations,such as nanoparticles,liposome complexes,micelles,and phospholipid complexes.Studies have shown that the anticancer effects of curcumin are mediated by its action on multiple molecular targets,including activator protein 1,protein kinase B(Akt),nuclear factorκ-light-chainenhancer of activated B cells,mitogen-activated protein kinase,epidermal growth factor receptor(EGFR)expression,and EGFR downstream signaling pathways.These targets play important roles in oral cancer pathogenesis,thereby making curcumin a promising adjuvant treatment modality.This review aims to summarize the different novel formulations of curcumin and their role in the treatment of oral cancer.展开更多
Macular edema such as diabetic macular edema(DME) and diabetic retinopathy are devastating back-of-theeye retinal diseases leading to loss of vision. This area is receiving considerable medical attention. Posterior oc...Macular edema such as diabetic macular edema(DME) and diabetic retinopathy are devastating back-of-theeye retinal diseases leading to loss of vision. This area is receiving considerable medical attention. Posterior ocular diseases are challenging to treat due to complex ocular physiology and barrier properties. Major ocular barriers are static(corneal epithelium, corneal stroma, and blood-aqueous barrier) and dynamic barriers(bloodretinal barrier, conjunctival blood flow, lymph flow, and tear drainage). Moreover, metabolic barriers impede posterior ocular drug delivery and treatment. To overcome such barriers and treat back-of-the-eye diseases, several strategies have been recently developed which include vitreal drainage, laser photocoagulation and treatment with biologics and/or small molecule drugs. In this article, we have provided an overview of several emerging novel strategies including nanotechnology based drug delivery approach for posterior ocular drug delivery and treatment with an emphasis on DME.展开更多
The periodic outbreak of mosquito-borne diseases like dengue fever,zika fever,and yellow fever all over the world highlights the need for effective mosquito control methods targeting the biological system.Due to the l...The periodic outbreak of mosquito-borne diseases like dengue fever,zika fever,and yellow fever all over the world highlights the need for effective mosquito control methods targeting the biological system.Due to the lack of therapeutic measures,preventive treatments or vaccines against pathogens,insecticide resistance eventually lead the research focus towards novel technological applications in mosquito management.Nanomaterials with ovicidal,larvicidal,adulticidal,and repellent properties for controlling mosquito vectors are under research.A literature search was carried out for advancements in nanomaterials,insecticides,and mosquito control in PubMed/MEDLINE,Scopus,Google Scholar,ScienceDirect,and Web of Science.This paper aims to provide insights into various nanomaterials relevant to mosquito-borne diseases,in vivo and in vitro toxicity evaluation against mosquito species,mode of action,effect on non-target organisms,and ecological risks.Organic and inorganic materials that provide controlled release,target delivery,less dosage,prolonged efficacy,a reduction in the use of organic solvents and emulsifiers,and minimum pollution to the environment have already been explored.Indeed,further research on the ecological risk and economic feasibility of nanomaterials in mosquitocidal applications should be done prior to commercialization.展开更多
Delivering therapeutics to the central nervous system（CNS） and brain-tumor has been a major challenge. The current standard treatment approaches for the brain-tumor comprise of surgical resection followed by immunot...Delivering therapeutics to the central nervous system（CNS） and brain-tumor has been a major challenge. The current standard treatment approaches for the brain-tumor comprise of surgical resection followed by immunotherapy, radiotherapy, and chemotherapy. However, the current treatments are limited in providing significant benefits to the patients and despite recent technological advancements; brain-tumor is still challenging to treat. Brain-tumor therapy is limited by the lack of effective and targeted strategies to deliver chemotherapeutic agents across the blood-brain barrier（BBB）. The BBB is the main obstacle that must be overcome to allow compounds to reach their targets in the brain. Recent advances have boosted the nanotherapeutic approaches in providing an attractive strategy in improving the drug delivery across the BBB and into the CNS. Compared to conventional formulations, nanoformulations offer significant ad vantages in CNS drug delivery approaches. Considering the above facts, in this review, the physiological/anatomical features of the brain-tumor and the BBB are briefly discussed. The drug transport mechanisms at the BBB are outlined. The approaches to deliver chemotherapeutic drugs across the CNS into the brain-tumor using nanocarriers are summarized. In addition, the challenges that need to be addressed in nanotherapeutic approaches for their enhanced clinical application in brain-tumor therapy are discussed.展开更多
According to the extent of fungal infections, to be chronic these such diseases and recently the emerging issue of increased antibiotic resistance in fungal infections, most of scientists are going to find a proper wa...According to the extent of fungal infections, to be chronic these such diseases and recently the emerging issue of increased antibiotic resistance in fungal infections, most of scientists are going to find a proper way to replace antibacterial agent by significant semiconductor ZnO nanoparticles (NPs). They are well known to be one of the most important and special metal oxide nanoparticles in pharmaceutical against the most common fungi. ZnO nanoparticles were synthesized using sol-gel, hydrothermal and functionalized surface methods and formulated in water solutions as nanofluids. XRD, FTIR and SEM techniques and UV-Vis absorbance spectroscopy characterized their ZnO modified nanostructures. Also antimycotic potential according to generally tests such as: (MIC) minimum inhibitory concentration, (MFC) minimum fungicidal concentration and normally well diffusion method with standard strains fungi were performed. Among five common fungi strains using in this research, new various ZnO nanofluids showed noticeable results for dermatophyte fungi like Trichophyton mentagrophytes, Microsporum gypseum, Microsporum canis, Candida albicans and Candid tropicalis which had un growth zones in order 70, 40, 35, 30 and 30 mm in comparing with Clotrimazole reference reagent: 30, 25, 25, 18 and 20 mm by well method. The performance of MIC for ZnO nanofluids on fungi was determined to be equal to 0.35, 3.12, 6.25, 6.25 and 6.25 μgr/ml and MFC of nanoproducts showed the 1.5, 12.5, 25, 25 and 25 μgr/ml. Therefore, the designed ZnO nanofluids could reveal the most effect on fungi which cause dermal (ringworm), mucosal (thrush) and vaginal infections, so we are able to apply these surface high energetic ZnO water-based nanofluid formulations as in vitro nanomedicine and nanohygiene for the first time.展开更多
Diabetes is a chronic metabolic disorder that affects millions of people worldwide and takes a heavy toll on human life. Treatment of diabetics often poses a problem in selection of the proper drug, its dose and unwan...Diabetes is a chronic metabolic disorder that affects millions of people worldwide and takes a heavy toll on human life. Treatment of diabetics often poses a problem in selection of the proper drug, its dose and unwanted side effects. Therefore, newer drugs with the least side effects but with highest efficiency are being relentlessly searched for. In recent years, nanotechnology has given new hope for the formulation of various drugs against a myriad of diseases, including diabetes. This review tries to give an overview of the advantages of various new drugs being used, including a wide range of nanoformulations of orthodox as well complementary and alternative medicines. Several studies and research reports based on nanotechnological approaches in the formulation of anti-diabetic drugs have pointed out the fact that research in the formulation of nanodrugs improved strategies for combating diabetes based on the plausible molecular mechanism of action of the drugs. Furthermore, attempts have also been made to delineate the optimum drug concentration and time of exposure in order to recommend a scientifically validated drug dose response in developing different therapeutic strategies. Thus, to a considerable extent, recent studies have contributed towards improving thelife expectancy and quality of life of diabetics, through both targeted orthodox medicine and complementary medicine, particularly those obtained from natural resources.展开更多
Over thousands of years,natural bioactive compounds derived from plants(bioactive phytocompounds,BPCs)have been used worldwide to address human health issues.Today,they are a significant resource for drug discovery in...Over thousands of years,natural bioactive compounds derived from plants(bioactive phytocompounds,BPCs)have been used worldwide to address human health issues.Today,they are a significant resource for drug discovery in the development of modern medicines.Although many BPCs have promising biological activities,most of them cannot be effectively utilized in drugs for therapeutic applications because of their inherent limitations of low solubility,structural instability,short half-life,poor bioavailability,and non-specific distribution to organs.Researchers have utilized emerging nanoformulation(NF)technologies to overcome these limitations as they have demonstrated great potential to improve the solubility,stability,and pharmacokinetic and pharmacodynamic characteristics of BPCs.This review exemplifies NF strategies for resolving the issues associated with BPCs and summarizes recent advances in their preclinical and clinical applications for imaging and therapy.This review also highlights how innovative NF technologies play a leading role in next-generation BPC-based drug development for extended therapeutic applications.Finally,this review discusses the opportunities to take BPCs with meaningful clinical impact from bench to bedside and extend the patent life of BPC-based medicines with new formulations or application to new adjacent diseases beyond the primary drug indications.展开更多
基金This work was supported by the National Natural Science Foundation of China[32101146,81974391,82072806,82173265]Shanghai Science and Technology Program[21010500100,22140901700]+5 种基金Basic Research Program of Shanghai Municipal Government[21JC1406002]Shanghai Pujiang Program[21PJ1404500]Shanghai Excellent Overseas Young Scientiststhe Clinical Research Plan of SHDC[SHDC2020CR4025]the Natural Science Foundation of Shanghai[20ZR1470500]Hospital Funded Clinical Research,Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine[21XHDB06].
文摘The approved worldwide use of two messenger RNA(mRNA)vaccines(BNT162b2 and mRNA-1273)in late 2020 has proven the remarkable success of mRNA therapeutics together with lipid nanoformulation technology in protecting people against coronaviruses during COVID-19 pandemic.This unprecedented and exciting dual strategy with nanoformulations and mRNA therapeutics in play is believed to be a promising paradigm in targeted cancer immunotherapy in future.Recent advances in nanoformulation technologies play a prominent role in adapting mRNA platform in cancer treatment.In this review,we introduce the biologic principles and advancements of mRNA technology,and chemistry fundamentals of intriguing mRNA delivery nanoformulations.We discuss the latest promising nano-mRNA therapeutics for enhanced cancer immunotherapy by modulation of targeted specific subtypes of immune cells,such as dendritic cells(DCs)at peripheral lymphoid organs for initiating mRNA cancer vaccine-mediated antigen specific immunotherapy,and DCs,natural killer(NK)cells,cytotoxic T cells,or multiple immunosuppressive immune cells at tumor microenvironment(TME)for reversing immune evasion.We highlight the clinical progress of advanced nano-mRNA therapeutics in targeted cancer therapy and provide our perspectives on future directions of this transformative integrated technology toward clinical implementation.
文摘The global incidence of oral cancer has steadily increased in recent years and is associated with high morbidity and mortality.Oral cancer is the most common cancer in the head and neck region,and is predominantly of epithelial origin(i.e.squamous cell carcinoma).Oral cancer treatment modalities mainly include surgery with or without radiotherapy and chemotherapy.Though proven effective,chemotherapy has significant adverse effects with possibilities of tumor resistance to anticancer drugs and recurrence.Thus,there is an imperative need to identify suitable anticancer therapies that are highly precise with minimal side effects and to make oral cancer treatment effective and safer.Among the available adjuvant therapies is curcumin,a plant polyphenol isolated from the rhizome of the turmeric plant Curcuma longa.Curcumin has been demonstrated to have antiinfectious,antioxidant,anti-inflammatory,and anticarcinogenic properties.Curcumin has poor bioavailability,which has been overcome by its various analogues and nanoformulations,such as nanoparticles,liposome complexes,micelles,and phospholipid complexes.Studies have shown that the anticancer effects of curcumin are mediated by its action on multiple molecular targets,including activator protein 1,protein kinase B(Akt),nuclear factorκ-light-chainenhancer of activated B cells,mitogen-activated protein kinase,epidermal growth factor receptor(EGFR)expression,and EGFR downstream signaling pathways.These targets play important roles in oral cancer pathogenesis,thereby making curcumin a promising adjuvant treatment modality.This review aims to summarize the different novel formulations of curcumin and their role in the treatment of oral cancer.
文摘Macular edema such as diabetic macular edema(DME) and diabetic retinopathy are devastating back-of-theeye retinal diseases leading to loss of vision. This area is receiving considerable medical attention. Posterior ocular diseases are challenging to treat due to complex ocular physiology and barrier properties. Major ocular barriers are static(corneal epithelium, corneal stroma, and blood-aqueous barrier) and dynamic barriers(bloodretinal barrier, conjunctival blood flow, lymph flow, and tear drainage). Moreover, metabolic barriers impede posterior ocular drug delivery and treatment. To overcome such barriers and treat back-of-the-eye diseases, several strategies have been recently developed which include vitreal drainage, laser photocoagulation and treatment with biologics and/or small molecule drugs. In this article, we have provided an overview of several emerging novel strategies including nanotechnology based drug delivery approach for posterior ocular drug delivery and treatment with an emphasis on DME.
文摘The periodic outbreak of mosquito-borne diseases like dengue fever,zika fever,and yellow fever all over the world highlights the need for effective mosquito control methods targeting the biological system.Due to the lack of therapeutic measures,preventive treatments or vaccines against pathogens,insecticide resistance eventually lead the research focus towards novel technological applications in mosquito management.Nanomaterials with ovicidal,larvicidal,adulticidal,and repellent properties for controlling mosquito vectors are under research.A literature search was carried out for advancements in nanomaterials,insecticides,and mosquito control in PubMed/MEDLINE,Scopus,Google Scholar,ScienceDirect,and Web of Science.This paper aims to provide insights into various nanomaterials relevant to mosquito-borne diseases,in vivo and in vitro toxicity evaluation against mosquito species,mode of action,effect on non-target organisms,and ecological risks.Organic and inorganic materials that provide controlled release,target delivery,less dosage,prolonged efficacy,a reduction in the use of organic solvents and emulsifiers,and minimum pollution to the environment have already been explored.Indeed,further research on the ecological risk and economic feasibility of nanomaterials in mosquitocidal applications should be done prior to commercialization.
文摘Delivering therapeutics to the central nervous system（CNS） and brain-tumor has been a major challenge. The current standard treatment approaches for the brain-tumor comprise of surgical resection followed by immunotherapy, radiotherapy, and chemotherapy. However, the current treatments are limited in providing significant benefits to the patients and despite recent technological advancements; brain-tumor is still challenging to treat. Brain-tumor therapy is limited by the lack of effective and targeted strategies to deliver chemotherapeutic agents across the blood-brain barrier（BBB）. The BBB is the main obstacle that must be overcome to allow compounds to reach their targets in the brain. Recent advances have boosted the nanotherapeutic approaches in providing an attractive strategy in improving the drug delivery across the BBB and into the CNS. Compared to conventional formulations, nanoformulations offer significant ad vantages in CNS drug delivery approaches. Considering the above facts, in this review, the physiological/anatomical features of the brain-tumor and the BBB are briefly discussed. The drug transport mechanisms at the BBB are outlined. The approaches to deliver chemotherapeutic drugs across the CNS into the brain-tumor using nanocarriers are summarized. In addition, the challenges that need to be addressed in nanotherapeutic approaches for their enhanced clinical application in brain-tumor therapy are discussed.
文摘According to the extent of fungal infections, to be chronic these such diseases and recently the emerging issue of increased antibiotic resistance in fungal infections, most of scientists are going to find a proper way to replace antibacterial agent by significant semiconductor ZnO nanoparticles (NPs). They are well known to be one of the most important and special metal oxide nanoparticles in pharmaceutical against the most common fungi. ZnO nanoparticles were synthesized using sol-gel, hydrothermal and functionalized surface methods and formulated in water solutions as nanofluids. XRD, FTIR and SEM techniques and UV-Vis absorbance spectroscopy characterized their ZnO modified nanostructures. Also antimycotic potential according to generally tests such as: (MIC) minimum inhibitory concentration, (MFC) minimum fungicidal concentration and normally well diffusion method with standard strains fungi were performed. Among five common fungi strains using in this research, new various ZnO nanofluids showed noticeable results for dermatophyte fungi like Trichophyton mentagrophytes, Microsporum gypseum, Microsporum canis, Candida albicans and Candid tropicalis which had un growth zones in order 70, 40, 35, 30 and 30 mm in comparing with Clotrimazole reference reagent: 30, 25, 25, 18 and 20 mm by well method. The performance of MIC for ZnO nanofluids on fungi was determined to be equal to 0.35, 3.12, 6.25, 6.25 and 6.25 μgr/ml and MFC of nanoproducts showed the 1.5, 12.5, 25, 25 and 25 μgr/ml. Therefore, the designed ZnO nanofluids could reveal the most effect on fungi which cause dermal (ringworm), mucosal (thrush) and vaginal infections, so we are able to apply these surface high energetic ZnO water-based nanofluid formulations as in vitro nanomedicine and nanohygiene for the first time.
文摘Diabetes is a chronic metabolic disorder that affects millions of people worldwide and takes a heavy toll on human life. Treatment of diabetics often poses a problem in selection of the proper drug, its dose and unwanted side effects. Therefore, newer drugs with the least side effects but with highest efficiency are being relentlessly searched for. In recent years, nanotechnology has given new hope for the formulation of various drugs against a myriad of diseases, including diabetes. This review tries to give an overview of the advantages of various new drugs being used, including a wide range of nanoformulations of orthodox as well complementary and alternative medicines. Several studies and research reports based on nanotechnological approaches in the formulation of anti-diabetic drugs have pointed out the fact that research in the formulation of nanodrugs improved strategies for combating diabetes based on the plausible molecular mechanism of action of the drugs. Furthermore, attempts have also been made to delineate the optimum drug concentration and time of exposure in order to recommend a scientifically validated drug dose response in developing different therapeutic strategies. Thus, to a considerable extent, recent studies have contributed towards improving thelife expectancy and quality of life of diabetics, through both targeted orthodox medicine and complementary medicine, particularly those obtained from natural resources.
基金supported by Basic Science Research Programs through the National Research Foundation of Korea(NRF)funded by the Ministry of Science and ICT(2017R1D1A1B03034888,2021R1A6A3A01086719 and 2015R1A6A3A04059033)a Korea Institute of Science and Technology(KIST)intramural research grant.
文摘Over thousands of years,natural bioactive compounds derived from plants(bioactive phytocompounds,BPCs)have been used worldwide to address human health issues.Today,they are a significant resource for drug discovery in the development of modern medicines.Although many BPCs have promising biological activities,most of them cannot be effectively utilized in drugs for therapeutic applications because of their inherent limitations of low solubility,structural instability,short half-life,poor bioavailability,and non-specific distribution to organs.Researchers have utilized emerging nanoformulation(NF)technologies to overcome these limitations as they have demonstrated great potential to improve the solubility,stability,and pharmacokinetic and pharmacodynamic characteristics of BPCs.This review exemplifies NF strategies for resolving the issues associated with BPCs and summarizes recent advances in their preclinical and clinical applications for imaging and therapy.This review also highlights how innovative NF technologies play a leading role in next-generation BPC-based drug development for extended therapeutic applications.Finally,this review discusses the opportunities to take BPCs with meaningful clinical impact from bench to bedside and extend the patent life of BPC-based medicines with new formulations or application to new adjacent diseases beyond the primary drug indications.
