Alginate-based functionalized, remote, light-responsive hydrogel transducer for synergistic mild photo thermoelectric...

Photothermal therapy (PTT) is an effective cancer treatment that circumvents the resistance caused by chemotherapy drugs. Conventional PTT has a relatively high temperature, which is better able to kill tumor tissues, but it is also more damaging to normal tissues. Mild PTT avoids these high temperatures, but its corresponding killing ability becomes lower and enhances the heat resistance of cancer cells, causing tumor self-protection and reducing the therapeutic effect of PTT. Here, we reported a new, remotely stimulable, mild-temperature PTT combined with electrical stimulation-induced ionic interference therapy. We introduced MXenes into alginate based thermoresponsive PVA/P(NIPAm-co-SA) hydrogel (PPS) to formulate mechanically reliable hydrogel electrolyte-based supercapacitors as an ion homeostasis perturbator. The artificially controlled duration of near-infrared radiation modulates the PTT cycle temperature, which is controllably maintained at a little under 45 °C to reduce Hsp90 overexpression. Light-induced phase transitions in the hydrogel produce voltages that resemble low-intensity, alternating electric fields. Moreover, chronic piezoelectric stimulation can inhibit cancer cell proliferation by upregulating the expression of genes encoding Kir3.2 inwardly rectifying potassium channels, by interfering with Ca²⁺ homeostasis, and by affecting mitotic spindle organization during mitosis. In vivo and in vitro antitumor studies on the 4T1 model suggest that this functionalized, remote, light-responsive transducer is an effective and promising tool for the treatment of tumors.