Transferrin-Conjugated Polymeric Nanoparticles via Polymerization-Induced Self-Assembly for Enhanced BBB Transport and Glioblastoma Therapy.
W, Z., LD, B., A, A., D, Z., X, C., CC, W., Z, T., NH, V., & L, E. (2026). Transferrin-Conjugated Polymeric Nanoparticles via Polymerization-Induced Self-Assembly for Enhanced BBB Transport and Glioblastoma Therapy.. ACS applied bio materials. https://doi.org/10.1021/acsabm.6c01007
W Z, LD B, A A, D Z, X C, CC W, et al. Transferrin-Conjugated Polymeric Nanoparticles via Polymerization-Induced Self-Assembly for Enhanced BBB Transport and Glioblastoma Therapy.. ACS applied bio materials. 2026; doi: 10.1021/acsabm.6c01007
W Z, LD B, A A, et al. Transferrin-Conjugated Polymeric Nanoparticles via Polymerization-Induced Self-Assembly for Enhanced BBB Transport and Glioblastoma Therapy.[J]. ACS applied bio materials. 2026. DOI: 10.1021/acsabm.6c01007.
@article{w2026,
author = {Zhang W and Blackman LD and Ardana A and Zhu D and Cheng X and Williams CC and Tong Z and Voelcker NH and Esser L},
title = {Transferrin-Conjugated Polymeric Nanoparticles via Polymerization-Induced Self-Assembly for Enhanced BBB Transport and Glioblastoma Therapy.},
journal = {ACS applied bio materials},
year = {2026},
doi = {10.1021/acsabm.6c01007},
note = {PMID: 42606070},
}
TY - JOUR AU - Zhang W AU - Blackman LD AU - Ardana A AU - Zhu D AU - Cheng X AU - Williams CC AU - Tong Z AU - Voelcker NH AU - Esser L TI - Transferrin-Conjugated Polymeric Nanoparticles via Polymerization-Induced Self-Assembly for Enhanced BBB Transport and Glioblastoma Therapy. T2 - ACS applied bio materials PY - 2026 DO - 10.1021/acsabm.6c01007 AN - PMID:42606070 ER -
Transferrin-coated nanoparticles show promise in delivering chemotherapeutic drugs across biological barriers for treating glioblastoma multiforme (GBM). Employing a synthetic approach integrating advanced chemistries and bespoke in vitro biological assays, we developed versatile transferrin-conjugated polymeric nanoparticles designed for both blood-brain barrier (BBB) penetration and GBM targeting. First, tunable azido-functional polymeric nanoparticles were synthesized through reversible addition-fragmentation chain-transfer (RAFT)-mediated polymerization-induced self-assembly (PISA). Subsequently, holo-transferrin, modified with a diarylcyclooctyne (DBCO)-modified polyethylene glycol (PEG) linker, was conjugated onto the polymeric nanoparticles through copper-free click chemistry. The transferrin-functionalized polymeric nanoparticles were conjugated with doxorubicin via a pH-sensitive imine bond and displayed a pH-responsive drug release. Evaluation of cellular targetability, cytocompatibility, cytotoxicity, and the anticancer effect on GBM after crossing the BBB was conducted through a series of in vitro platforms of increasing physiological complexity: 2D cell culture, a static Transwell model, and a dynamic microfluidic BBB-GBM-on-a-chip model, utilizing immortalized human brain microvascular endothelial cells (hCMEC/D3) and malignant glioma cells (U87-MG). Our results demonstrate the potential of the transferrin-conjugated polymeric nanoparticles in facilitating doxorubicin delivery across the BBB and enhancing cytotoxicity on GBM while concurrently mitigating the adverse side effects on the BBB associated with free doxorubicin.