Work

Tunable sericin nanocarriers for controlled drug release and glioblastoma targeting

Year: 2025

Type: article

Abstract: • ATRP grafting of PDMAEMA onto sericin tailors nanoparticle size and surface charge. • Nanoprecipitation produces stable, uniform sericin nanocarriers with low aggregation. • Nanocarriers show pH- and enzyme-responsive drug release matching tumor conditions. • Temozolomide-loaded nanocarriers show superior in vitro cytotoxicity against glioblastoma cells. • In vivo studies confirm biocompatibility and minimal systemic toxicity of nanocarriers. Glioblastoma multiforme (GBM) is among the most aggressive and lethal brain tumors, presenting formidable clinical challenges due to its rapid progression, resistance to conventional therapies, and the restrictive nature of the blood-brain barrier (BBB). To address these obstacles, we developed innovative pH-responsive polymer-protein hybrid nanocarriers designed for precise and efficient drug delivery to glioblastoma tissues. In this work, silk sericin, a natural glycoprotein, was biofunctionalized with poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) chains via atom transfer radical polymerization (ATRP), creating well-defined macromolecular architectures. Two synthetic pathways were explored, yielding nanocarriers with tunable side-chain lengths and distinct physicochemical properties. Nanoparticles were fabricated through rapid nanoprecipitation, producing self-assembled structures with controlled sizes ranging from 25 to 90 nm. Comprehensive characterization using FTIR-ATR, Raman, NMR, XPS, SEM, and DLS confirmed successful synthesis, structural integrity, and favorable morphology. The nanocarriers demonstrated efficient encapsulation of anticancer drugs, temozolomide and 5-fluorouracil, and exhibited pH-sensitive release profiles replicating the tumor microenvironment. Biological evaluation revealed significant cytotoxicity against human glioblastoma LN-229 cells in vitro, while in vivo studies in mice indicated good biocompatibility and minimal systemic toxicity. These findings underscore the potential of biofunctionalized sericin-polymer nanocarriers as versatile platforms for targeted, stimuli-responsive drug delivery across the BBB, offering promising avenues for advancing glioblastoma therapy and overcoming current treatment limitations.

Source: Results in Engineering

DOI: 10.1016/j.rineng.2025.108569