Transferrin-Conjugated Polymeric Nanoparticles via Polymerization-Induced Self-Assembly for Enhanced BBB Transport and Glioblastoma Therapy.

Authors

Weisen Zhang, Lewis D Blackman, Aditya Ardana, Douer Zhu, Xuan Cheng, Charlotte C Williams, Ziqiu Tong, Nicolas H Voelcker, Lars Esser

Published in

ACS applied bio materials. Volume 9. Issue 16. Pages 7616-7628. Aug 17, 2026.

Abstract

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.

PMID:
42606070
Bibliographic data and abstract were imported from PubMed on 17 Aug 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.