Abstract
We report the synthesis of polymeric conjugates designed to penetrate the blood–brain barrier (BBB) and selectively bind glioblastoma (GBM) cells through reversible addition–fragmentation chain transfer (RAFT) polymerization. The resulting materials were engineered to contain peptide macromonomers for cell-specific targeting and integrated DOTA units to facilitate radiolabeling with copper-64 (64Cu), yielding radiolabeled conjugates with greater than 95% radiochemical purity. In biodistribution assessments conducted in mice, C1C2 peptide-conjugated polymers showed significantly improved accumulation in brain tissue, supported by brain perfusion analyses confirming efficient BBB penetration. Additionally, flow cytometry evaluations demonstrated specific affinity of GBM-targeted polymer formulations toward U87 glioblastoma cells. Overall, these polymer–peptide conjugates particularly the C1C2-functionalized variant demonstrate notable promise for targeted imaging and therapy of glioblastoma, providing a foundation for future preclinical development.
Recommended Citation
C. A. Wieczorek Villas Boas et al., "Polymeric Nanocarriers Functionalized with Peptides for Improved Glioblastoma Targeting and Blood–Brain Barrier Permeability," Bioconjugate Chemistry, vol. 36, no. 8, pp. 1639 - 1648, American Chemical Society, Aug 2025.
The definitive version is available at https://doi.org/10.1021/acs.bioconjchem.5c00119
Department(s)
Materials Science and Engineering
International Standard Serial Number (ISSN)
1520-4812; 1043-1802
Document Type
Article - Journal
Document Version
Citation
File Type
text
Language(s)
English
Rights
© 2025 American Chemical Society, All rights reserved.
Publication Date
20 Aug 2025
PubMed ID
40773766
Comments
Centro de Investigação em Biomedicina, Grant None