Skip to content
DraconiticResearch
Search Sources API
201,683 studies31 sourcesUpdated 19 min ago
Peer-reviewedCC BY 4.0ACS Omega

Pretransplant Bioconjugation of Renal Endothelial Surfaces for TAK-242 Drug Delivery

  • Michael Nicosia1
  • Johann W. Karunananthan2
  • Isaiah A. Rivera2
  • William M. Baldwin1
  • Ran Fan1
  • Victoria Gorbacheva1
  • Jose I. Valenzuela1
  • Rahul N. Gaykar2
  • Anna Valujskikh1
  • Robert R. Kane2
  1. 1Cleveland Clinic , , , ,
  2. 2Baylor University , , , ,
Open at sourcePDFDOICite

Abstract

Transplantation provides a unique opportunity wherein donor tissue is isolated ex vivo and available for tissue-specific manipulation prior to implantation. We previously demonstrated improved graft performance with covalently modified drug-eluting islets. In this work we provide preliminary studies extending the concept of covalent tissue modification for drug delivery to renal transplantation and demonstrate that the perfusion of reactive N-hydroxysuccinimide (NHS) esters through the renal artery affords the covalent modification of kidney vascular surfaces. The fluorescent labeling of vascular surface proteins has minimal impact on clinical markers of kidney function and host immune responses in murine isografts and allografts over 5 weeks. Additionally, histological analysis of modified graft tissue resected on day 35 reveals no gross abnormalities, with some covalent label still detectable. In a preliminary study, bioconjugation of renal vasculature with a slow-release prodrug of TAK-242 (a potent inhibitor of toll-like receptor 4) modulated the expression of inflammatory cytokines and reduced T-cell infiltration into graft tissue 48 h posttransplant.

Related

  1. Electrochemical Tryptophan-Selective Bioconjugation in Neutral Buffer via Cooperative N -Oxyl Radicals
    Ryo Kuroda, Eisho Toyama, Moe Toyobe +12
    Bioconjugate ChemistryPeer-reviewedLicence not statedFull text5 citedOrganic chemistryOpenAlex
  2. Molecular Engineering of Sarcosine Oxidase and Horseradish Peroxidase: Impact of Lysine Accessibility on Covalent Bioconjugation and Bioelectrocatalysis
    Kamilė Ratkevičiu̅tė, Simonas Grybas, Ondrej Šedo +3
    ACS OmegaPeer-reviewedCC BY 4.0Full textGeneral chemistryCrossref
  3. A Ruthenium(CAAC‐5) Olefin Metathesis Catalyst for Bioconjugation
    Damian Alexander Graf, Mikhail Boym, María Álvarez +2
    Angewandte Chemie (International Ed. in English)Peer-reviewedCC BY 4.0Full textOrganic chemistryPMC
  4. Electronically tuned N-terminal glycine selective bioconjugation enables in vitro and in vivo species-specific Staphylococcus aureus targeting
    Mohan Kumar, Divya Bindra, Ashish Verma +11
    Nature CommunicationsPeer-reviewedCC BY-NC-ND 4.0Full textOrganic chemistryCrossrefEurope PMCPMC
  5. Green Extraction and Molecular Docking-Guided Discovery of Asiaticoside as a Multi-Target Modulator of the SIRT1/HMGB1/p53-p21 Axis in H2O2-Induced Senescent Endothelial Cells
    Wenkai Li, Jianhua Huang, Fei Zeng +4
    Molecules (Basel, Switzerland)Peer-reviewedCC BYFull textGeneral chemistryEurope PMC

Cite

BibTeXRIS
BibTeX
@article{nicosia2026pretransplant,
  title = {{Pretransplant Bioconjugation of Renal Endothelial Surfaces for TAK-242 Drug Delivery}},
  author = {Michael Nicosia and Johann W. Karunananthan and Isaiah A. Rivera and William M. Baldwin and Ran Fan and Victoria Gorbacheva and Jose I. Valenzuela and Rahul N. Gaykar and Anna Valujskikh and Robert R. Kane},
  journal = {ACS Omega},
  year = {2026},
  month = oct,
  doi = {10.1021/acsomega.6c07422},
  url = {https://pubs.acs.org/acsodf/article/doi/10.1021/acsomega.6c07422/5461360/Pretransplant-Bioconjugation-of-Renal-Endothelial},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Pretransplant Bioconjugation of Renal Endothelial Surfaces for TAK-242 Drug Delivery
AU  - Michael Nicosia
AU  - Johann W. Karunananthan
AU  - Isaiah A. Rivera
AU  - William M. Baldwin
AU  - Ran Fan
AU  - Victoria Gorbacheva
AU  - Jose I. Valenzuela
AU  - Rahul N. Gaykar
AU  - Anna Valujskikh
AU  - Robert R. Kane
PY  - 2026
DA  - 2026/10/30
JO  - ACS Omega
DO  - 10.1021/acsomega.6c07422
UR  - https://pubs.acs.org/acsodf/article/doi/10.1021/acsomega.6c07422/5461360/Pretransplant-Bioconjugation-of-Renal-Endothelial
AB  - Transplantation provides a unique opportunity wherein donor tissue is isolated ex vivo and available for tissue-specific manipulation prior to implantation. We previously demonstrated improved graft performance with covalently modified drug-eluting islets. In this work we provide preliminary studies extending the concept of covalent tissue modification for drug delivery to renal transplantation and demonstrate that the perfusion of reactive N-hydroxysuccinimide (NHS) esters through the renal artery affords the covalent modification of kidney vascular surfaces. The fluorescent labeling of vascular surface proteins has minimal impact on clinical markers of kidney function and host immune responses in murine isografts and allografts over 5 weeks. Additionally, histological analysis of modified graft tissue resected on day 35 reveals no gross abnormalities, with some covalent label still detectable. In a preliminary study, bioconjugation of renal vasculature with a slow-release prodrug of TAK-242 (a potent inhibitor of toll-like receptor 4) modulated the expression of inflammatory cytokines and reduced T-cell infiltration into graft tissue 48 h posttransplant.
SN  - 2470-1343
ER  -