Multifunctional gold nanorods in low-temperature photothermal interactions for combined tumor starvation and RNA interference therapy

Collateral damage to healthy tissue, uneven heat distribution, inflammatory diseases, and tumor metasta-sis induction hinder the translation of high-temperature photothermal therapy (PTT) from bench to prac-tical clinical applications. In this report, a multifunctional gold nanorod (GNR)-based nanosystem was designed by attaching siRNA against B7-H3 (B7-H3si), glucose oxidase (GOx), and hyaluronic acid (HA) for efficient low-temperature PTT. Herein, GOx can not only exhaust glucose to induce starvation ther-apy but also reduce the heat shock protein (HSP), realizing the ablation of tumors without damage to healthy tissues. Evidence shows that B7-H3, a type I transmembrane glycoprotein molecule, plays essen-tial roles in growth, metastasis, and drug resistance. By initiating the downregulation of B7-H3 by siRNA, siRNA-GOx/GNR@HA NPs may promote the effectiveness of treatment. By targeting cluster of differenti-ation 44 (CD44) and depleting B7-H3 and HSPs sequentially, siRNA-GOx/GNR@HA NPs showed 12.9-fold higher lung distribution than siRNA-GOx/GNR NPs. Furthermore, 50% of A549-bearing mice in the siRNA-GOx/GNR NPs group survived over 50 days. Overall, this low-temperature phototherapeutic nanosystem provides an appropriate strategy for eliminating cancer with high treatment effectiveness and minimal systemic toxicity.To realize efficient tumor ablation under mild low-temperature (42-45 degrees C) and RNA interference si-multaneously, here we developed a multifunctional gold nanorod (GNR)-based nanosystem (siRNA-GOx/GNR@HA NPs). This nanoplatform can significantly inhibit tumor cell proliferation and induce cell apoptosis by downregulation of HSP90 alpha, HSP70, B7-H3, p-AKT, and p-ERK and upregulation of cleaved caspase-9 at mild low-temperature due to its superior tumor homing ability and the combined effect of photothermal effect, glucose deprivation-initiated tumor starvation, and B7-H3 gene silence effect. It is believed that this multifunctional low-temperature photothermal nanosystem with efficient and specific anticancer properties, shows a potential application in clinical tumor treatment. (c) 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.