Polydopamine-coated nucleic acid nanogel for siRNA-Mediated low-temperature photothermal therapy

Abstract Photothermal therapy (PTT) normally requires to maintain the temperature of tumor lesions above 50 °C, which potentially induces local inflammation and tumor metastasis. To avoid these side effects, it is vital to achieve effective antitumor efficacy at relatively low temperature (42–45 °C) during the PTT treatment. Herein, we design a polydopamine (PDA)-coated nucleic acid nanogel as a therapeutic complex for siRNA-mediated low-temperature PTT. First, siRNAs that target the heat-shock-protein 70 (Hsp70) serve as crosslinkers to guide the DNA-grafted polycaprolactone (DNA-g-PCL) assemble into nanosized hydrogel particles through nucleic acid hybridization. Thereafter, the obtained siRNA-embedded nanogels are further coated with a thin layer of polydopamine, which not only protects the nanogels against enzymatic degradation but also endows the nanogels with excellent photothermal conversion capacity under near infrared (NIR) light irradiation. After surface PEGylation, this triple shield siRNA delivery complex shows the capability of effective ablating the tumor under relatively mild condition.