Polyglycerol-Grafted Graphene Oxide with pH-Responsive Charge-Convertible Surface to Dynamically Control the Nanobiointeractions for Enhanced in Vivo Tumor Internalization.

Fiche publication

Date publication

juin 2025

Journal

Small (Weinheim an der Bergstrasse, Germany)

Auteurs

Membres identifiés du Cancéropôle Est :
Dr BIANCO Alberto

Tous les auteurs :
Zou Y, Bianco A, Nishina Y

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/40450710

Résumé

pH-responsive charge-convertible nanomaterials (NMs) ameliorate the treatment of cancer via simultaneously reducing nonspecific interactions during systemic circulation and improving targeted uptake within solid tumors. While promising, little is known about how the pH-responsiveness of charge-convertible NMs directs their interactions with biological systems, leading to compromised performance, including off-target retention and low specificity to tumor cells. In the present study, polyglycerol-grafted graphene oxide bearing amino groups (GOPGNH) at different densities are reacted with dimethylmaleic anhydride (DMMA), a pH-responsive moiety, to generate a set of charge-convertible GOPGNH-DMMA variants. This permits the assessment of a quantitative correlation between the structure of GOPGNH-DMMA to their pH-responsiveness, their dynamic interactions with proteins and cells, as well as their in vivo biological fate. Through a systematic investigation, it is revealed that GOPGNH115-DMMA prepared from GOPGNH with higher amine density experienced fast charge conversion at pH 7.4 to induce non-specific interactions at early stages, whereas GOPGNH60-DMMA and GOPGNH30-DMMA prepared from lower amine density retarded off-target charge conversion to enhance tumor accumulation. Notably, GOPGNH60-DMMA is also associated with enough amounts of proteins under acidic conditions to promote in vivo tumor internalization. The findings will inform the design of pH-responsive NMs for enhanced treatment accuracy and efficacy.