Microfluidics-based fabrication and targeted motion control of multimodal therapeutic hydrogel capsule microrobots

Abstract

In cancer combination therapy, micro-robot systems that integrate multiple therapeutic functions have emerged as a key direction for overcoming the limitations of traditional treatments. This study proposes a magnetic thermosensitive hydrogel capsule micro-robot that combines both drug-targeted delivery within blood vessels and local magnetic hyperthermia therapy. By introducing acrylamide and sodium alginate to modify the poly(N-isopropyl acrylamide) hydrogel system, the thermal response characteristics and drug-loading capacity of the micro-robot carrier are optimized. A multi-coaxial co-flow microfluidic chip is employed to achieve the directed encapsulation of Fe₃O₄ nanoparticles and the rapid, controlled preparation of single-core and core–shell structured spherical micro-robots. The core–shell structure enables the simultaneous loading of hydrophilic and hydrophobic drugs. Under the influence of a high-frequency alternating magnetic field, the local temperature around the micro-robot increased from 21 °C to 42 °C within 4 minutes, successfully triggering the phase transition contraction of the hydrogel and releasing the drug while also reaching the temperature threshold for thermal therapy. Additionally, this study established a visual feedback, magnetically driven system, with the micro-robot achieving a maximum movement speed of 3.47 mm s⁻¹ under a magnetic field strength of 7.4 mT, thereby realizing millimeter-level positioning accuracy and complex curve trajectory tracking in vascular microchannels that simulate a blood environment. Experimental results indicate that the prepared multimodal hydrogel capsule microrobots possess excellent targeted movement capabilities, meeting the functional requirements for a synergistic “thermotherapy-chemotherapy” treatment, and demonstrate potential application in the development of low-toxicity, high-efficiency tumor combination therapy.