The knowledge of interactions among functional proteins helps researchers understand disease mechanisms and design potential strategies for treatment.As a general approach,the fluorescent and affinity tags were employ...The knowledge of interactions among functional proteins helps researchers understand disease mechanisms and design potential strategies for treatment.As a general approach,the fluorescent and affinity tags were employed for exploring this field by labeling the Protein of Interest(POI).However,the autofluorescence and weak binding strength significantly reduce the accuracy and specificity of these tags.Conversely,HaloTag,a novel self-labeling enzyme(SLE)tag,could quickly form a covalent bond with its ligand,enabling fast and specific labeling of POI.These desirable features greatly increase the accuracy and specificity,making the HaloTag a valuable system for various applications ranging from imaging to immobilization of POI.Notably,the HaloTag technique has already been successfully employed in a series of studies with excellent efficiency.In this review,we summarize the development of HaloTag and recent advanced investigations associated with HaloTag,including in vitro imaging(e.g.,POI imaging,cellular condition monitoring,microorganism imaging,system development),in vivo imaging,biomolecule immobilization(e.g.,POI collection,protein/nuclear acid interaction and protein structure analysis),targeted degradation(e.g.,L-AdPROM),and more.We also present a systematic discussion regarding the future direction and challenges of the HaloTag technique.展开更多
With the advent of precision medicine and personalized treatment,targeted therapies have become pivotal in oncology.Noninvasive molecular imaging,especially immunoPET/SPECT,plays a crucial role in refining cancer diag...With the advent of precision medicine and personalized treatment,targeted therapies have become pivotal in oncology.Noninvasive molecular imaging,especially immunoPET/SPECT,plays a crucial role in refining cancer diagnostics and treatment monitoring by visualizing biological processes at the molecular level.This review explores the dynamic field of immunoPET/SPECT imaging using Fab and F(ab′)_(2) fragments,characterized by advantageous pharmacokinetics and swift clearance from the bloodstream,making them suitable for same-day imaging procedures.We examine contemporary strategies for radiolabeling these fragments with PET and SPECT radionuclides and discuss potential advancements and the challenges anticipated in the further development of Fab and F(ab′)_(2) fragments.Despite the complexities involved in their development,these fragments hold significant promise for advanceing personalized cancer treatment.Keys to this advancement are innovative radiolabeling techniques,site-specific conjugation chemistries,and short-lived radionuclides,all of which are crucial for overcoming existing limitations and enhancing the clinical utility of these imaging agents.As research progresses,Fab and F(ab′)_(2) fragments are expected to become central to the future of cancer diagnostics and therapeutic monitoring,thereby improving patient management and contributing significantly to the evolution of personalized medicine.展开更多
DNA tetrahedro n nano structure (DTN) is one of the simplest DNA nano structures and has bee n successfully applied for biose nsin g, imagi ng, and treatment of can cer. To facilitate its biomedical applications and p...DNA tetrahedro n nano structure (DTN) is one of the simplest DNA nano structures and has bee n successfully applied for biose nsin g, imagi ng, and treatment of can cer. To facilitate its biomedical applications and pote ntial clinical tran slation, fun dame ntal un derstandi ng of DTN's transportation among major organs in living organisms becomes increasingly important. Here, we describe the efficient renal clearanee of DTN in healthy mice by using positron emission tomography (PET) imaging. The kidney elimination of DTN was later applied for renal function evaluation in murine models of unilateral ureteral obstruction (UUO). We further established a mathematical program of DTN to validate its changes of transportation pattern in healthy and UUO mice. We believe the establishment of pharmacokinetic profiles and mathematical model of DTN may provide in sight for future optimization of DNA nano structures for biomedical applications.展开更多
Acute kidney injury(AKI)leads to unacceptably high mortality due to difficulties in timely intervention and less efficient renal delivery of therapeutic drugs.Here,a series of polyvinylpyrrolidone(PVP)-curcumin nanopa...Acute kidney injury(AKI)leads to unacceptably high mortality due to difficulties in timely intervention and less efficient renal delivery of therapeutic drugs.Here,a series of polyvinylpyrrolidone(PVP)-curcumin nanoparticles(PCurNP)are designed to meet the renal excretion threshold(~45 kDa),presenting a controllable delivery nanosystem for kidney targeting.Renal accumulation of the relatively small nanoparticles,^(89)Zr-PCurNP M10 with the diameter between 5 and 8 nm,is found to be 1.7 times and 1.8 times higher than the accumulation of^(89)Zr-PCurNP M29(20-50 nm)and M40(20-50 nm)as revealed by PET imaging.Furthermore,serum creatinine analysis,kidney tissues histology,and tubular injury scores revealed that PCurNP M10 efficiently treated cisplatin-induced AKI.Herein,PCurNP offers a novel and simple strategy for precise PET image-guided drug delivery of renal protective materials.展开更多
Spherical nucleic acids(SNAs)are composed of a nanoparticle core and a layer of densely arranged oligonucleotide shells.After the first report of SNA by Mirkin and coworkers in 1996,it has created a significant intere...Spherical nucleic acids(SNAs)are composed of a nanoparticle core and a layer of densely arranged oligonucleotide shells.After the first report of SNA by Mirkin and coworkers in 1996,it has created a significant interest by offering new possibilities in the field of gene and drug delivery.The controlled aggregation of oligonucleotides on the surface of organic/inorganic nanoparticles improves the delivery of genes and nucleic acid–based drugs and alters and regulates the biological profiles of the nanoparticle core within living organisms.Here in this review,we present an overview of the recent progress of SNAs that has speeded up their biomedical application and their potential transition to clinical use.We start with introducing the concept and characteristics of SNAs as drug/gene delivery systems and highlight recent efforts of bioengineering SNA by imaging and treatmenting various diseases.Finally,we discuss potential challenges and opportunities of SNAs,their ongoing clinical trials,and future translation,and how they may affect the current landscape of clinical practices.We hope that this review will update our current understanding of SNA,organized oligonucleotide aggregates,for disease diagnosis and treatment.展开更多
Brachytherapy is an established treatment modality that has been globally utilized for the therapy of malignant solid tumors.However,classic therapeutic sealed sources used in brachytherapy must be surgically implante...Brachytherapy is an established treatment modality that has been globally utilized for the therapy of malignant solid tumors.However,classic therapeutic sealed sources used in brachytherapy must be surgically implanted directly into the tumor site and removed after the requisite period of treatment.In order to avoid the trauma involved in the surgical procedures and prevent undesirable radioactive distribution at the cancerous site,well-dispersed radiolabeled nanomaterials are now being explored for brachytherapy applications.This emerging ffeld has been coined“nanoscale brachytherapy”.Despite present-day advancements,an ongoing challenge is obtaining an advanced,functional nanomaterial that concurrently incorporates features of high radiolabeling yield,short labeling time,good radiolabeling stability,and long tumor retention time without leakage of radioactivity to the nontargeted organs.Further,attachment of suitable targeting ligands to the nanoplatforms would widen the nanoscale brachytherapy approach to tumors expressing various phenotypes.Molecular imaging using radiolabeled nanoplatforms enables noninvasive visualization of cellular functions and biological processes in vivo.In vivo imaging also aids in visualizing the localization and retention of theradiolabeled nanoplatforms at the tumor site for the requisite time period to render safe and effective therapy.Herein,we review theadvancements over the last several years in the synthesis and use of functionalized radiolabeled nanoplatforms as a noninvasivesubstitute to standard brachytherapy sources.The limitations of present-day brachytherapy sealed sources are analyzed,whilehighlighting the advantages of using radiolabeled nanoparticles(NPs)for this purpose.The recent progress in the development ofdifferent radiolabeling methods,delivery techniques and nanoparticle internalization mechanisms are discussed.The preclinicalstudies performed to date are summarized with an emphasis on the current challenges toward the future translation of nanoscalebrachytherapy in routine clinical practices.展开更多
基金The authors are grateful for financial support from the University of Wisconsin—Madison and National Institutes of Health(P30CA014520).
文摘The knowledge of interactions among functional proteins helps researchers understand disease mechanisms and design potential strategies for treatment.As a general approach,the fluorescent and affinity tags were employed for exploring this field by labeling the Protein of Interest(POI).However,the autofluorescence and weak binding strength significantly reduce the accuracy and specificity of these tags.Conversely,HaloTag,a novel self-labeling enzyme(SLE)tag,could quickly form a covalent bond with its ligand,enabling fast and specific labeling of POI.These desirable features greatly increase the accuracy and specificity,making the HaloTag a valuable system for various applications ranging from imaging to immobilization of POI.Notably,the HaloTag technique has already been successfully employed in a series of studies with excellent efficiency.In this review,we summarize the development of HaloTag and recent advanced investigations associated with HaloTag,including in vitro imaging(e.g.,POI imaging,cellular condition monitoring,microorganism imaging,system development),in vivo imaging,biomolecule immobilization(e.g.,POI collection,protein/nuclear acid interaction and protein structure analysis),targeted degradation(e.g.,L-AdPROM),and more.We also present a systematic discussion regarding the future direction and challenges of the HaloTag technique.
基金supported by the University of Wisconsin-Madison and the National Institutes of Health(P30 CA014520&T32 CA009206,USA)the National Natural Science Foundation of China(82472018,82171970)+4 种基金Beijing Nova Program(20240484725)Beijing Municipal Science&Technology Commission(Z221100007422027,China)National Key Research and Development Program of China(2024YFE0113500)National High Level Hospital Clinical Research Funding(Interdisciplinary Research Project of Peking University First Hospital,2023IR17,2024IR07Scientific and Technological Achievements Transformation Incubation Guidance Fund Project of Peking University First Hospital,2024CX18,China).
文摘With the advent of precision medicine and personalized treatment,targeted therapies have become pivotal in oncology.Noninvasive molecular imaging,especially immunoPET/SPECT,plays a crucial role in refining cancer diagnostics and treatment monitoring by visualizing biological processes at the molecular level.This review explores the dynamic field of immunoPET/SPECT imaging using Fab and F(ab′)_(2) fragments,characterized by advantageous pharmacokinetics and swift clearance from the bloodstream,making them suitable for same-day imaging procedures.We examine contemporary strategies for radiolabeling these fragments with PET and SPECT radionuclides and discuss potential advancements and the challenges anticipated in the further development of Fab and F(ab′)_(2) fragments.Despite the complexities involved in their development,these fragments hold significant promise for advanceing personalized cancer treatment.Keys to this advancement are innovative radiolabeling techniques,site-specific conjugation chemistries,and short-lived radionuclides,all of which are crucial for overcoming existing limitations and enhancing the clinical utility of these imaging agents.As research progresses,Fab and F(ab′)_(2) fragments are expected to become central to the future of cancer diagnostics and therapeutic monitoring,thereby improving patient management and contributing significantly to the evolution of personalized medicine.
基金University of Wisconsin-Madison, the National Institutes of Health (NIBIB/NCI P30CA014520, T32CA009206)the American Cancer Society (125246-RSG-13- 099-01-CCE), the National Natural Science Foundation of China (Nos. 51573096, 51703132, 31771036, and 81630049)+2 种基金the Basic Research Program of Shenzhen (Nos. JCYJ20170412111100742 and JCYJ20160422091238319)the Guangdong Province Natural Science Foundation of Major Basic Research and Cultivation Project (No. 2018B030308003)Fok Ying-Tong Education Foundation for Young Teachers in the Higher Education Institutions of China (No. 161032).
文摘DNA tetrahedro n nano structure (DTN) is one of the simplest DNA nano structures and has bee n successfully applied for biose nsin g, imagi ng, and treatment of can cer. To facilitate its biomedical applications and pote ntial clinical tran slation, fun dame ntal un derstandi ng of DTN's transportation among major organs in living organisms becomes increasingly important. Here, we describe the efficient renal clearanee of DTN in healthy mice by using positron emission tomography (PET) imaging. The kidney elimination of DTN was later applied for renal function evaluation in murine models of unilateral ureteral obstruction (UUO). We further established a mathematical program of DTN to validate its changes of transportation pattern in healthy and UUO mice. We believe the establishment of pharmacokinetic profiles and mathematical model of DTN may provide in sight for future optimization of DNA nano structures for biomedical applications.
基金supported by the National Natural Science Foundation of China(81601605,21571147,82102121)the Postdoctoral Science Foundation of China(2016M600670)+2 种基金supported by the University of Wisconsin–Madison,the National Institutes of Health(NIBIB/NCI P30CA014520)the Natural Science Foundation of SZU(Grant No.827-000143)the Shenzhen Peacock Plan(KQTD2016053112051497).
文摘Acute kidney injury(AKI)leads to unacceptably high mortality due to difficulties in timely intervention and less efficient renal delivery of therapeutic drugs.Here,a series of polyvinylpyrrolidone(PVP)-curcumin nanoparticles(PCurNP)are designed to meet the renal excretion threshold(~45 kDa),presenting a controllable delivery nanosystem for kidney targeting.Renal accumulation of the relatively small nanoparticles,^(89)Zr-PCurNP M10 with the diameter between 5 and 8 nm,is found to be 1.7 times and 1.8 times higher than the accumulation of^(89)Zr-PCurNP M29(20-50 nm)and M40(20-50 nm)as revealed by PET imaging.Furthermore,serum creatinine analysis,kidney tissues histology,and tubular injury scores revealed that PCurNP M10 efficiently treated cisplatin-induced AKI.Herein,PCurNP offers a novel and simple strategy for precise PET image-guided drug delivery of renal protective materials.
基金Wuhan Union Hospital,the University of Wisconsin-Madison,the National Institutes of Health,Grant/Award Number:P30CA014520National Natural Science Foundation of China,Grant/Award Numbers:81501532,82071968Yellow Crane Talent(Science&Technology)Program of Wuhan City。
文摘Spherical nucleic acids(SNAs)are composed of a nanoparticle core and a layer of densely arranged oligonucleotide shells.After the first report of SNA by Mirkin and coworkers in 1996,it has created a significant interest by offering new possibilities in the field of gene and drug delivery.The controlled aggregation of oligonucleotides on the surface of organic/inorganic nanoparticles improves the delivery of genes and nucleic acid–based drugs and alters and regulates the biological profiles of the nanoparticle core within living organisms.Here in this review,we present an overview of the recent progress of SNAs that has speeded up their biomedical application and their potential transition to clinical use.We start with introducing the concept and characteristics of SNAs as drug/gene delivery systems and highlight recent efforts of bioengineering SNA by imaging and treatmenting various diseases.Finally,we discuss potential challenges and opportunities of SNAs,their ongoing clinical trials,and future translation,and how they may affect the current landscape of clinical practices.We hope that this review will update our current understanding of SNA,organized oligonucleotide aggregates,for disease diagnosis and treatment.
基金support from the Bhabha Atomic Research Centre,the University of Wiscon-sin〓〓Madison,and the National Institutes of Health(P30 CA014520 and T32 CA009206).
文摘Brachytherapy is an established treatment modality that has been globally utilized for the therapy of malignant solid tumors.However,classic therapeutic sealed sources used in brachytherapy must be surgically implanted directly into the tumor site and removed after the requisite period of treatment.In order to avoid the trauma involved in the surgical procedures and prevent undesirable radioactive distribution at the cancerous site,well-dispersed radiolabeled nanomaterials are now being explored for brachytherapy applications.This emerging ffeld has been coined“nanoscale brachytherapy”.Despite present-day advancements,an ongoing challenge is obtaining an advanced,functional nanomaterial that concurrently incorporates features of high radiolabeling yield,short labeling time,good radiolabeling stability,and long tumor retention time without leakage of radioactivity to the nontargeted organs.Further,attachment of suitable targeting ligands to the nanoplatforms would widen the nanoscale brachytherapy approach to tumors expressing various phenotypes.Molecular imaging using radiolabeled nanoplatforms enables noninvasive visualization of cellular functions and biological processes in vivo.In vivo imaging also aids in visualizing the localization and retention of theradiolabeled nanoplatforms at the tumor site for the requisite time period to render safe and effective therapy.Herein,we review theadvancements over the last several years in the synthesis and use of functionalized radiolabeled nanoplatforms as a noninvasivesubstitute to standard brachytherapy sources.The limitations of present-day brachytherapy sealed sources are analyzed,whilehighlighting the advantages of using radiolabeled nanoparticles(NPs)for this purpose.The recent progress in the development ofdifferent radiolabeling methods,delivery techniques and nanoparticle internalization mechanisms are discussed.The preclinicalstudies performed to date are summarized with an emphasis on the current challenges toward the future translation of nanoscalebrachytherapy in routine clinical practices.
