Bioconjugate Chemistry最新文献

{"title":"Tumor Cell Membrane Biomimetic Mesoporous Silicon Materials in Combination with PD-L1 Knockout Achieved through the CRISPR/Cas9 System for Targeted and Immunotherapeutic Purposes","authors":"Jinjin Zhao,&nbsp;Xiaorou Wang,&nbsp;Haiguang Zhang,&nbsp;Qunmei Zhang,&nbsp;DeYing Bo,&nbsp;Hua Zhong,&nbsp;Luyang Jiao*,&nbsp;Hongchang Yuan* and Guangjian Lu*,&nbsp;","doi":"10.1021/acs.bioconjchem.5c0000110.1021/acs.bioconjchem.5c00001","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00001https://doi.org/10.1021/acs.bioconjchem.5c00001","url":null,"abstract":"<p >Nanoparticle-based drug delivery systems, which enable the effective and targeted delivery of chemotherapeutic drugs to tumors, have revolutionized cancer therapy. Mesoporous silicon materials (MSN) have emerged as promising candidates for drug delivery due to their unique properties. The therapeutic efficacy can be significantly enhanced when treatments exhibit both targeting and antiphagocytic properties. In this study, cell membranes extracted from B16–F10 cells were used to encapsulate carboplatin (CBP)-loaded MSN via physical extrusion. Additionally, we intratumorally injected a plasmid containing the CRISPR/Cas9 system to achieve PD-L1 knockout, thereby reactivating the immune system. The cell membrane coating endowed the CBP@MSN with excellent slow-release capability and cytocompatibility. Enhanced tumor cell uptake of CBP@MSN@M was observed due to homologous targeting by cancer cell membranes. Moreover, CBP@MSN@M demonstrated enhanced antitumor efficacy in vivo and promoted the proliferation of immune cells. Finally, the antitumor effect was further improved by the knockout of PD-L1 within the tumor microenvironment. These results suggest that the newly prepared CBP@MSN@M, combined with PD-L1 knockout, holds significant potential as an effective therapeutic approach for treating tumors.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"36 5","pages":"971–979 971–979"},"PeriodicalIF":4.0,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144098092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>E. coli</i> as a Smart Thermo-Vector for Combating Solid Tumors: A Synergistic Heat-Induced Cancer Therapy Approach.","authors":"Tashmeen Kaur, Neeta Devi, Deepika Sharma","doi":"10.1021/acs.bioconjchem.5c00102","DOIUrl":"10.1021/acs.bioconjchem.5c00102","url":null,"abstract":"<p><p>Heat-induced cancer therapies such as magnetic hyperthermia-based cancer therapy (MHCT) and photothermal tumor ablation (PTT) have garnered significant attention as minimally invasive new-generation cancer therapy modalities. However, solid tumors associated with hypoxia present a considerable challenge to effective cancer therapy. In this study, we took up the challenge of mitigating the limiting penetration ability of nanoparticles by integrating polydopamine-coated magnetic nanoparticles and motile anaerobic bacteria (PDBs) to function as a smart thermo-vector. The developed PDBs are capable of self-navigating hypoxic tumors and as thermo-therapy agents with the ability to induce heat through exposure to an alternating magnetic field or near-infrared laser light. The thermo-vector system exhibited a dual-functioning synergistic antitumor effect of MHCT and PTT and an outstanding tumor targeting efficiency, outperforming the conventional 'nanoparticles only' approach. The heat-induced cellular oxidative stress and disrupted mitochondrial function led to 80% cellular cytotoxicity within 24 h of treatment. The PDB-based approach led to complete tumor regression in c57BL/6 mice within 21 days of treatment and a tumor-free survival for 60 days without recurrence, proving the capability of the developed PDBs in combatting solid tumors.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"867-880"},"PeriodicalIF":4.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic Characterization of the Potency of THIOMAB Antibody-Drug Conjugates Targeting <i>Staphylococcus aureus</i> and ETbR-Expressing Tumor Cells Using Quantitative LC-MS/MS Analysis of Intracellular Drug Accumulation.","authors":"Hilda Hernandez-Barry, Josefa Dela Cruz-Chuh, Kimberly K Kajihara, Jyoti Asundi, Richard Vandlen, Donglu Zhang, Wouter L W Hazenbos, Thomas Pillow, Yichin Liu, Cong Wu, Katherine R Kozak, Kelly M Loyet","doi":"10.1021/acs.bioconjchem.4c00533","DOIUrl":"10.1021/acs.bioconjchem.4c00533","url":null,"abstract":"<p><p>THIOMAB drug conjugate (TDC) technology provides site-specific conjugation of linker drugs to antibodies, allowing for targeted delivery of the payload. While a direct measurement of TDC cytotoxic potency allows efficient screening and confirmation that new drugs conjugated to antibodies result in proper processing in cells, additional mechanistic characterization is often needed to provide information-rich data to guide further optimization of TDC design. For example, a quantitative understanding of how TDCs are processed intracellularly can help determine which processing step is impacting payload delivery and thereby inform the basis of the TDC efficacy. Here, we measure the cellular accumulation of two different TDC drug payloads: MAPK (mitogen-activated protein kinase) pathway inhibitor targeting ETbR-expressing tumor cells and an antibiotic active against <i>Staphylococcus aureus</i> with an <i>in vitro</i> cell-based drug release LC-MS/MS assay in a 96-well format. This assay allowed us to correlate the cellular potency of each unconjugated molecule with the amount of payload that accumulated inside the cell. In the case of the pathway inhibitor drug, the biochemical characterization of TDC processing by cathepsin B and purified human liver enzyme extract demonstrated a correlation between the efficiency of the linker drug cleavage and intracellular payload accumulation. For the antibody-antibiotic conjugate, kinetic analysis of intracellular free drug retention provided valuable insight into the chemistry modifications needed for an efficient TDC. Taken together, we demonstrated the utility of quantitative LC-MS/MS assays as one tool in guiding the design of more effective TDCs via the mechanistic release characterization of two distinct payloads.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"652-661"},"PeriodicalIF":4.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12007502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted Polymersomes Enable Enhanced Delivery to Peripheral Nerves Post-Injury.","authors":"Kayleigh Trumbull, Sophia Fetten, Noah Arnold, Vanessa Marahrens, Dru Montgomery, Olivia Myers, Jeffery L Twiss, Jessica Larsen","doi":"10.1021/acs.bioconjchem.5c00072","DOIUrl":"10.1021/acs.bioconjchem.5c00072","url":null,"abstract":"<p><p>The gold standard therapy for peripheral nerve injuries involves surgical repair, which is invasive and leads to major variations in therapeutic outcomes. Because of this, smaller injuries often go untreated. However, alternative, noninvasive routes of administration are currently unviable due to the presence of the blood-nerve barrier (BNB), which prevents passage of small molecules from the blood into the endoneurium and the nerve. This paper demonstrates that ligands on the surface of nanoparticles, called polymersomes, can enable delivery to the nerve through noninvasive intramuscular injections. Polymersomes made from polyethylene glycol (PEG)-<i>b</i>-polylactic acid (PLA) were conjugated with either apolipoprotein E (ApoE) or rabies virus glycoprotein-based peptide RVG29 (RVG) and loaded with near-infrared dye, AlexaFluor647. ApoE was used to target receptors upregulated in post-injury inflammation, while RVG targets neural-specific receptors. Untagged, ApoE-tagged, and RVG-tagged polymersomes were injected at 100 mM either intranerve (IN) or intramuscular (IM) into Sprague-Dawley rats post sciatic nerve injury. The addition of the ApoE and RVG tags enabled increased AlexaFluor647 fluorescence in the injury site at 1 h post IN injection compared to the untagged polymersome control. However, only the RVG-tagged polymersomes increased the AlexaFluor647 fluorescence after IM injection. Ex vivo analysis of sciatic nerves demonstrated that ApoE-tagged polymersomes enabled the greatest retention of AlexaFluor647 regardless of the injection route. This led us to conclude that using ApoE to target inflammation enabled the greatest retention of polymersome-delivered payloads while using RVG to target neural cells more specifically enabled the penetration of polymersome-delivered payloads. Observations were confirmed by calculating the area under the curve pharmacokinetic parameters and the use of a two-compartment pharmacokinetic model.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"823-837"},"PeriodicalIF":4.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AIE Photosensitizer with Tuned Membrane Interactions for Effective-Gram-Negative Bacteria Elimination.","authors":"Edward Kamya, Shangzhao Yi, Zhongzhong Lu, Jincong Yan, Hewan Dawit, Shah Mehmood, Yi Cao, Renjun Pei","doi":"10.1021/acs.bioconjchem.5c00132","DOIUrl":"10.1021/acs.bioconjchem.5c00132","url":null,"abstract":"<p><p>Photodynamic antimicrobial therapy (PDAT) for efficient bacterial infection eradication critically relies on photosensitizers (PSs) that can specifically target and disrupt bacterial membranes. However, the complex membrane architecture of Gram-negative bacteria poses a significant challenge to the efficacy of most aggregation-induced emission (AIE) PSs. Herein, we introduce TPQ, an AIE PS meticulously designed to overcome this challenge by incorporating an outer membrane disruption ability, thereby boosting PDAT efficacy against Gram-negative bacteria. TPQ demonstrated excellent microbial imaging and potent PDAT activity against both Gram-positive and Gram-negative bacteria, attributed to its inherent fluorescence, high singlet oxygen generation, and balanced electrostatic and hydrophobic interactions with bacterial membranes. Notably, TPQ achieved exceptional PDAT activity (>97% efficacy) against Gram-negative bacteria while exhibiting minimal cytotoxicity to mammalian cells. Furthermore, TPQ-mediated PDAT effectively healed <i>Escherichia coli</i>-infected wounds on mice models with assured biosafety. This work provides valuable insights into the rational design of AIE PSs and highlights the synergistic effect of membrane disruption for advancing PDAT applications, particularly against recalcitrant Gram-negative bacterial infections.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"881-891"},"PeriodicalIF":4.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exceptional Near-Infrared II Organic Small Molecule Nanoagent for Photoacoustic/Photothermal Imaging-Guided Highly Efficient Therapy in Cancer.","authors":"Yidong Bin, Lixian Huang, Jiangke Qin, Shulin Zhao, Jianniao Tian, Liangliang Zhang","doi":"10.1021/acs.bioconjchem.5c00058","DOIUrl":"10.1021/acs.bioconjchem.5c00058","url":null,"abstract":"<p><p>Near-infrared II (NIR-II) photoacoustic (PA)/photothermal imaging-guided tumor therapy holds great promise in precision medicine for cancer treatment. This work reports on the synthesis and application of an organic small molecule nanoagent that has exceptional PA and photothermal properties in the near-infrared region. BCy-TPE was constructed by linking an NIR-II absorbing cyanine dye BCy-Cl with a twisted tetraphenylethene unit. The synthesized BCy-TPE exhibited an intense absorption peak at 1032 nm. After encapsulation into water-dispersible nanoparticles (NPs), BCy-TPE NPs exhibited two absorption peaks at 880 and 1046 nm. Notably, under 1064 nm laser excitation, BCy-TPE NPs deliver a remarkable photothermal conversion efficiency of 92%, together with superior biocompatibility, photostability, and PA/photothermal imaging capability. Moreover, after intravenous administration of BCy-TPE NPs into 4T1 tumor-bearing mice and treatment with safe-intensity (1.0 W cm^-2 and 1064 nm) laser irradiation, tumor temperature increased rapidly to 52 °C within 1 min and tumors are completely ablated after a single photothermal therapy treatment. Overall, this work offers a novel strategy to develop superb NIR-II photothermal agents for PA/photothermal imaging-guided highly efficient therapy in cancer.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"803-814"},"PeriodicalIF":4.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aptamer- vs Fab-Conjugated Liposomes: A Comparative Study in Targeting Acute Myeloid Leukemia Cells.","authors":"Hyesoo Jin, Wooseong Noh, Kangwuk Kyung, Woon-Seok Yeo, Ye Han Song, Yong-Seok Heo, Dong-Eun Kim","doi":"10.1021/acs.bioconjchem.5c00065","DOIUrl":"10.1021/acs.bioconjchem.5c00065","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) is a hematologic malignancy characterized by uncontrolled proliferation of abnormal myeloid cells with a generally poor prognosis despite advancements in chemotherapy and stem cell transplantation. To enhance therapeutic efficacy and minimize systemic toxicity, we designed liposomal nanoparticles functionalized with two distinct targeting ligands, a DNA aptamer or fragment-antigen-binding (Fab) antibody, targeting the surface marker transmembrane glycoprotein CD33 antigen (CD33) on AML cells. Aptamer- and Fab-conjugated liposomes (Apt-Lipm and Fab-Lipm, respectively) were prepared and tested for cellular uptake by CD33-positive AML cell lines. Comparative studies revealed that Fab-Lipm exhibited significantly superior binding affinity, targeting efficiency, and cellular uptake compared with Apt-Lipm. Furthermore, we demonstrated the intracellular distribution and endocytic pathways of Fab-Lipm during the cellular uptake. This comparative study of aptamer- and Fab-conjugated liposomes suggests that the Fab-conjugated liposomal system offers enhanced precision in targeting AML cells for the development of effective therapeutic strategies against hematologic malignancies.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"815-822"},"PeriodicalIF":4.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Receptor-Mediated Transmembrane Activation of Protein Folding in Synthetic Cells.","authors":"Andreas Bo Tker Pedersen, Dante Guldbrandsen Andersen, Josefine Hammer Jakobsen, Mireia Casanovas Montasell, Alexander N Zelikin","doi":"10.1021/acs.bioconjchem.5c00043","DOIUrl":"10.1021/acs.bioconjchem.5c00043","url":null,"abstract":"<p><p>Synthetic cells are a rapidly maturing platform with emerging applications in biomedicine and biotechnology. The specific novelty of this work is that we develop synthetic cells that respond to an extracellular stimulus by performing the folding of an encapsulated polypeptide into a functional enzyme. To this end, we developed artificial transmembrane signaling receptors. These contain an extracellular enzyme-responsive group, a self-immolative linker as the mechanism of signal transduction, and a secondary messenger molecule with intracellular activity. The secondary messenger is chosen such that it initiates protein refolding from the denatured polypeptide. Results of this study expand the molecular toolbox for the design of synthetic cells with life-like, responsive behavior.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"782-791"},"PeriodicalIF":4.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of PSMA-Targeted TREN-CAM Conjugates for Targeted Imaging of Cancer with ⁶⁸Ga(III) and ⁴⁵Ti(IV).","authors":"Axia Marlin, Phuong Nguyen Tran, Morgan Dierolf, Molly DeLuca, M Andrey Joaqui Joaqui, Owen M Glaser, Angus J Koller, Eduardo Alucio-Sarduy, Mallory Gork, Dariusz Śmiłowicz, Valérie Pierre, Jonathan W Engle, Eszter Boros","doi":"10.1021/acs.bioconjchem.5c00099","DOIUrl":"10.1021/acs.bioconjchem.5c00099","url":null,"abstract":"<p><p>Chelation approaches that are compatible with a multitude of isotopes are an important area of development. Here, we introduce the design, synthesis, and evaluation of 2,3-dihydroxyterephthalate/catechol chelator conjugates compatible with the positron emission tomography (PET) isotopes ⁶⁸Ga³⁺ and ⁴⁵Ti⁴⁺, targeting the prostate-specific membrane antigen (PSMA). The conjugates are made in a multistep organic synthesis incorporating 2,3-dihydroxyterephthalate, linked to the amino hexanoic acid-extended, urea-dipeptides EuE or KuE (substrates of the PSMA active site). The radiochemical complexes, [⁴⁵Ti][Ti(TREN-CAM-hex-EuE)]^2-, [⁴⁵Ti][Ti(TREN-CAM-hex-KuE)]^2-, and [⁶⁸Ga][Ga(TREN-CAM-hex-KuE)]^3- form readily at room temperature within 15 min with a molar activity of 24-29 mCi/μmol. The corresponding chelates are stable in phosphate-buffered saline (PBS) solution prior to injection. Subsequent in vivo studies in a bilateral tumor xenograft mouse model were conducted, including 90- and 270-min PET, followed by biodistribution and metabolite analysis at 2 or 5 h postinjection. These studies demonstrated selective uptake of the radiochemical complexes in the PSMA-expressing tumor (17.25 ± 4.15, 13.84 ± 3.85, 15.64 ± 6.37% ID/g for [⁴⁵Ti][Ti(TREN-CAM-hex-EuE)]^2-, [⁴⁵Ti][Ti(TREN-CAM-hex-KuE)]^2- and [⁶⁸Ga][Ga(TREN-CAM-hex-KuE)]^3- respectively), with pharmacokinetics dominated by renal clearance. Delayed clearance of the [⁴⁵Ti][Ti(TREN-CAM-hex-KuE)]^2- complex is observed when compared with that of [⁶⁸Ga][Ga(TREN-CAM-hex-KuE)]^3- as indicated by elevated activity retention in the blood, which we attribute to the charge difference and partial complex dissociation. Urine metabolite analysis shows that [⁶⁸Ga][Ga(TREN-CAM-hex-KuE)]^3- is excreted >98% intact, while [⁴⁵Ti][Ti(TREN-CAM-hex-KuE)]^2- exhibited signs of dechelation. Conclusively, our data support further investigation of bifunctional TREN-CAM derivatives as a synthetically accessible bifunctional chelator class for ⁶⁸Ga³⁺ and ⁴⁵Ti⁴⁺ isotopes.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"859-866"},"PeriodicalIF":4.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Copper Complexes with New Glycyl-l-histidyl-l-lysine-Hyaluronan Conjugates Show Antioxidant Properties and Osteogenic and Angiogenic Synergistic Effects.","authors":"Valentina Greco, Valeria Lanza, Barbara Tomasello, Irina Naletova, Warren R L Cairns, Sebastiano Sciuto, Enrico Rizzarelli","doi":"10.1021/acs.bioconjchem.4c00545","DOIUrl":"10.1021/acs.bioconjchem.4c00545","url":null,"abstract":"<p><p>In recent years, hyaluronic acid (HA) and the natural tripeptide glycyl-l-histidyl-l-lysine (GHK), especially its copper(II) complex (GHK-Cu), individually have been shown to exert helpful properties for bone protection and regeneration. However, they are not strong enough to handle oxidative stress, hydrolytic attack, or environmental conditions. Being aware that conjugation chemistry has recently emerged as an appealing approach for generating new molecular entities capable of preserving the molecular integrity of their moieties or delaying their degradation, herein we present the synthesis of conjugates of HA with GHK (GHK-HA), at different loadings of the tripeptide. GHK-HA binds copper(II) ions and potentiates the chemical and biological properties of the two components in in vitro assays. The results highlight copper's role in promoting the expression and release of certain trophic, angiogenic, and osteogenic factors, including brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), as well as bone morphogenetic protein-2 (BMP-2). The protective and regenerative activities of the metal ion are related to the translocation of its intracellular chaperones Copper Chaperone for Superoxide Dismutase (CCS) and Antioxidant-1 (Atox1) to the nucleus where they act as transcription factors.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"662-675"},"PeriodicalIF":4.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}