Intracerebral hemorrhage(ICH)is a subtype of stroke associated with higher rates of mortality.Currently,no effective drug treatment is available for ICH.The molecular pathways following ICH are complicated and diverse...Intracerebral hemorrhage(ICH)is a subtype of stroke associated with higher rates of mortality.Currently,no effective drug treatment is available for ICH.The molecular pathways following ICH are complicated and diverse.Nucleic acid therapeutics such as gene knockdown by small interfering RNAs(siRNAs)have been developed in recent years to modulate ICH’s destructive pathways and mitigate its outcomes.However,siRNAs delivery to the central nervous system is challenging and faces many roadblocks.Existing barriers to systemic delivery of siRNA limit the use of naked siRNA;therefore,siRNA-vectors developed to protect and deliver these therapies into the specific-target areas of the brain,or cell types seem quite promising.Efficient delivery of siRNA via nanoparticles emerged as a viable and effective alternative therapeutic tool for central nervous system-related diseases.This review discusses the obstacles to siRNA delivery,including the advantages and disadvantages of viral and nonviral vectors.Additionally,we provide a comprehensive overview of recent progress in nanotherapeutics areas,primarily focusing on the delivery system of siRNA for ICH treatment.展开更多
Melanoma,a highly malignant and complex form of cancer,has increased in global incidence,with a growing number of new cases annually.Active targeting strategies,such as leveraging theα-melanocyte-stimulating hormone(...Melanoma,a highly malignant and complex form of cancer,has increased in global incidence,with a growing number of new cases annually.Active targeting strategies,such as leveraging theα-melanocyte-stimulating hormone(αMSH)and its interaction with the melanocortin 1 receptor(MC1R)overexpressed in melanoma cells,enhance the concentration of therapeutic agents at tumor sites.For instance,targeted delivery of plasmonic light-sensitive agents and precise hyperthermia management provide an effective,minimally invasive treatment for tumors.In this work,we present a comparative study on targeted photothermal therapy(PTT)using plasmonic gold nanorods(Au NRs)as a robust and safe nanotool to reveal how key treatment parameters affect therapy outcomes.Using an animal model(B16-F10)of melanoma tumors,we compare the targeting abilities of Au NRs modified with two different MC1R agonists,either closely mimicking theαMSH sequence or providing a superior functionalization extent of Au NRs(4.5%(w/w)versus 1.8%(w/w)),revealing 1.6 times better intratumoral localization.Following theoretical and experimental assessments of the heating capabilities of the developed Au NRs under laser irradiation in either the femtosecond(FS)-or nanosecond(NS)-pulsed regime,we perform targeted PTT employing two types of peptide-modified Au NRs and compare therapeutic outcomes revealing the most appropriate PTT conditions.Our investigation reveals greater heat release from Au NRs under irradiation with FS laser,due to the relaxation rates of the electron and phonon temperatures dissipating in the surrounding,which correlates with a more pronounced 17.6 times inhibition of tumor growth when using FS-pulsed regime.展开更多
Messenger RNA(mRNA)has drawn much attention in the medical field.Through various treatment approaches including protein replacement therapies,gene editing,and cell engineering,mRNA is becoming a potential therapeutic ...Messenger RNA(mRNA)has drawn much attention in the medical field.Through various treatment approaches including protein replacement therapies,gene editing,and cell engineering,mRNA is becoming a potential therapeutic strategy for cancers.However,delivery of mRNA into targeted organs and cells can be challenging due to the unstable nature of its naked form and the low cellular uptake.Therefore,in addition to mRNA modification,efforts have been devoted to developing nanoparticles for mRNA delivery.In this review,we introduce four categories of nanoparticle platform systems:lipid,polymer,lipid-polymer hybrid,and protein/peptide-mediated nanoparticles,together with their roles in facilitating mRNA-based cancer immunotherapies.We also highlight promising treatment regimens and their clinical translation.展开更多
基金A Scholarship supported Daniyah Almarghalani from Taif University,Saudi Arabia Cultural Missionsupported by the grants from American Heart Association#17AIREA33700076/ZAS/2017the National Institute of Neurological Disorders and Stroke of the National Institutes of Health#R01NS112642 to ZAS.
文摘Intracerebral hemorrhage(ICH)is a subtype of stroke associated with higher rates of mortality.Currently,no effective drug treatment is available for ICH.The molecular pathways following ICH are complicated and diverse.Nucleic acid therapeutics such as gene knockdown by small interfering RNAs(siRNAs)have been developed in recent years to modulate ICH’s destructive pathways and mitigate its outcomes.However,siRNAs delivery to the central nervous system is challenging and faces many roadblocks.Existing barriers to systemic delivery of siRNA limit the use of naked siRNA;therefore,siRNA-vectors developed to protect and deliver these therapies into the specific-target areas of the brain,or cell types seem quite promising.Efficient delivery of siRNA via nanoparticles emerged as a viable and effective alternative therapeutic tool for central nervous system-related diseases.This review discusses the obstacles to siRNA delivery,including the advantages and disadvantages of viral and nonviral vectors.Additionally,we provide a comprehensive overview of recent progress in nanotherapeutics areas,primarily focusing on the delivery system of siRNA for ICH treatment.
基金Part of this work related to the synthesis of nanomaterials by the Russian Science Foundation(project no.24-75-10006)Part of this work related to the biological experiments was supported by the Russian Science Foundation(project no.21-75-30020)+4 种基金Part of this work related to the characterization of nanomaterials was supported by the Ministry of Science and Higher Education of Russia(grant number 075-15-2021-1349)The authors acknowledge the Clover Program and the Priority 2030 Federal Academic Leadership ProgramThe authors acknowledge Lidia Pogorelskaya for the proof-reading of the manuscriptThe authors acknowledge the Nanotechnology Centre of SPbSU for electron microscopy studiesThe work was partially performed at the ITMO Core Facility Center“Nanotechnologies”.
文摘Melanoma,a highly malignant and complex form of cancer,has increased in global incidence,with a growing number of new cases annually.Active targeting strategies,such as leveraging theα-melanocyte-stimulating hormone(αMSH)and its interaction with the melanocortin 1 receptor(MC1R)overexpressed in melanoma cells,enhance the concentration of therapeutic agents at tumor sites.For instance,targeted delivery of plasmonic light-sensitive agents and precise hyperthermia management provide an effective,minimally invasive treatment for tumors.In this work,we present a comparative study on targeted photothermal therapy(PTT)using plasmonic gold nanorods(Au NRs)as a robust and safe nanotool to reveal how key treatment parameters affect therapy outcomes.Using an animal model(B16-F10)of melanoma tumors,we compare the targeting abilities of Au NRs modified with two different MC1R agonists,either closely mimicking theαMSH sequence or providing a superior functionalization extent of Au NRs(4.5%(w/w)versus 1.8%(w/w)),revealing 1.6 times better intratumoral localization.Following theoretical and experimental assessments of the heating capabilities of the developed Au NRs under laser irradiation in either the femtosecond(FS)-or nanosecond(NS)-pulsed regime,we perform targeted PTT employing two types of peptide-modified Au NRs and compare therapeutic outcomes revealing the most appropriate PTT conditions.Our investigation reveals greater heat release from Au NRs under irradiation with FS laser,due to the relaxation rates of the electron and phonon temperatures dissipating in the surrounding,which correlates with a more pronounced 17.6 times inhibition of tumor growth when using FS-pulsed regime.
基金support from the Maximizing Investigators'Research Awards(R35GM119679,USA)and(R35GM144117,USA)from the National Institute of General Medical Sciences。
文摘Messenger RNA(mRNA)has drawn much attention in the medical field.Through various treatment approaches including protein replacement therapies,gene editing,and cell engineering,mRNA is becoming a potential therapeutic strategy for cancers.However,delivery of mRNA into targeted organs and cells can be challenging due to the unstable nature of its naked form and the low cellular uptake.Therefore,in addition to mRNA modification,efforts have been devoted to developing nanoparticles for mRNA delivery.In this review,we introduce four categories of nanoparticle platform systems:lipid,polymer,lipid-polymer hybrid,and protein/peptide-mediated nanoparticles,together with their roles in facilitating mRNA-based cancer immunotherapies.We also highlight promising treatment regimens and their clinical translation.
