Ultrasound assisted continuous flow synthesis and surface functionalization of polymeric nanospheres for targeted nanomedicine

Abstract

Polymeric nanospheres with narrow size distribution and composition are attractive building blocks for advanced nanomedicine applications, particularly in targeted drug delivery. This work report a continuous and controllable strategy for the synthesis of polymeric nanospheres (PNSs) based on the integration of ultrasound-assisted emulsification with a flow reactor system. Ultrasound irradiation enables the formation of a stable and homogeneous nanoemulsion, while the flow reactor ensures precise control over polymerization conditions. Systematic optimization of key parameters, including temperature, residence time, and monomer concentration, yields narrowly dispersed PNSs with tunable physicochemical properties. The resulting nanospheres were characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS), confirming their uniform size distribution and well-defined morphology. Furthermore, the PNSs were successfully functionalized with FITC-conjugated monoclonal antibodies targeting plasma membrane-bound Hsp70, generating anti-mHsp70-FITC-mAbs@PNSs. This functionalization tested on mHsp70-positive glioma C6 cells demonstrates the suitability of the platform for bioconjugation and targeted delivery applications. Overall, this study highlights a process intensified approach on ultrasound-assisted continuous flow reactor based synthesis as a scalable and versatile approach for producing functional PNSs for biomedical and drug delivery applications. © 2026 Elsevier B.V.