Self-Assembly-Based Nanoprobes for the Simultaneous Detection and Downregulation of HSP90 alpha mRNA to Enhance Photothermal Therapy

Although photothermal therapy (PTT) has been widely applied for tumor treatment, tumor cells thermotolerance still limits PTT efficiency. Since the overexpressed HSP90 alpha in tumor cells further enhances thermotolerance and protects them from PTT damage, a new nanoprobe that can specifically detect and down regulate HSP90 alpha mRNA was developed to enhance the PTT effect. Based on the HSP90 alpha mRNA sequence, the nanoprobe Au-DNA1/ DNA2 can specifically bind to HSP90 alpha mRNA for recovering its fluorescence and further inhibit the synthesis of HSP90 alpha to reduce tumor heat tolerance. Moreover, another nanoprobe, Au-DNA3, can self-assemble with the Au-DNA1 nanoprobe after the detection to form Au aggregations to enhance PTT afterward for better efficiency. Simultaneously, such a design improves tissue penetration and tumor retention, thereby reducing the damage to the surrounding normal tissues. Both in vitro and in vivo experiments showed that the nanoprobes have excellent tumor diagnosis and cancer treatment capabilities, which is of great significance for clinical translational applications.