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

Mesoporous silica nanoparticles (MSNs) are attractive drug delivery carriers, and green synthesis from biowaste offers an eco-friendly alternative to conventional methods. Unlike previous studies limited to a single precursor, this work systematically compares multiple biosources, including rice husk (RH), wheat husk (WH), wheat stalk (WS), oat husk (OH), oat stalk (OS), and horsetail (HT), and establishes a standardized route to evaluate precursor influence. Among the tested precursors, RH and HT produced the highest purity silica and were selected for MSN synthesis. The resulting MSNs showed well-defined mesoporosity, high surface area, and controlled pore sizes, confirmed by FTIR, XRD, BET, and HR-TEM with pH-responsive Dox release enhanced under acidic conditions. They were biocompatible with HDFs, HUVECs, and U87 cells, while Dox-loaded MSNs exhibited strong anticancer effects against U87 cells at low drug concentration. 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 and U87. 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.