Green synthesized mesoporous silica nanoparticles offer a promising drug delivery system investigated in physiologically relevant 3D microfluidic models

Mesoporous silica nanoparticles (MSNs) are promising drug delivery carriers due to their high surface area, tunable pore size, and loading capacity. Green synthesis from biowaste provides an eco-friendly alternative to conventional methods, yet most studies rely on a single precursor, limiting systematic evaluation. Here, we compared multiple biosources, including rice husk (RH), wheat husk (WH), wheat stalk (WS), oat husk (OH), oat stalk (OS), and horsetail (HT), and established a standardized route for MSN synthesis to consistently assess precursor influence. Among the tested materials, RH and HT yielded the highest purity and quantity of silica and were therefore selected for subsequent MSN synthesis. This green approach not only reduces environmental burdens but also adds value to agricultural and industrial waste streams. The prepared MSNs were thoroughly characterized, and their physicochemical properties were compared to assessing the influence of precursor type on nanoparticle performance. The synthesized MSNs exhibited well-defined mesoporous structures, high surface area, and controlled pore sizes, as confirmed by FTIR, XRD, BET, and HR-TEM analyses. Doxorubicin (Dox) loading and release studies revealed a pH-responsive profile, with enhanced drug release under acidic tumor-like conditions. Biocompatibility assessments via MTT assays showed no significant cytotoxicity in human fibroblasts (HDFs), endothelial cells (HUVECs), and human glioblastoma cells (U87). Furthermore, Dox-loaded MSNs demonstrated a rapid therapeutic effect against U87 cells at very low drug concentrations. The second novelty lies in evaluating MSN cellular uptake under physiologically relevant conditions using a microfluidic platform that mimics blood circulation, in contrast to conventional static assays. Cellular uptake was analyzed in 2D cultures and 3D microfluidic models, incorporating both static and dynamic conditions using HUVECs (normal cells) and U87 (cancer cells). Notably, the dynamic 3D model, which simulates blood circulation, significantly enhanced MSN uptake by HUVECs and U87 compared to static conditions. These results emphasize the importance of physiological flow in optimizing nanoparticle-based drug delivery. This study introduces a dual innovation by establishing a consistent, multi-biosource approach for green MSN synthesis and validating their drug delivery potential in a realistic dynamic microenvironment, bridging sustainable nanomaterial development with advanced preclinical testing.