Self-Assembly-Based Nanoprobes for the Simultaneous Detection and Downregulation of HSP90α mRNA to Enhance Photothermal Therapy

Abstract

Although photothermal therapy (PTT) has been widely applied for tumor treatment, tumor cells thermotolerance still limits PTT efficiency. Since the overexpressed HSP90α in tumor cells further enhances thermotolerance and protects them from PTT damage, a new nanoprobe that can specifically detect and downregulate HSP90α mRNA was developed to enhance the PTT effect. Based on the HSP90α mRNA sequence, the nanoprobe Au-DNA1/DNA2 can specifically bind to HSP90α mRNA for recovering its fluorescence and further inhibit the synthesis of HSP90α 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.

RNA-cleaving DNAzymes for accurate biosensing and gene therapy

“…97 Several studies proposed that heat shock proteins (HSPs), especially HSP70 and HSP90, are the key defense molecules of tumor thermoresistance and endow cancer cells with high resistance to heat. [98][99][100] Based on this, our laboratory constructed an HSP70 targeting DNAzymebased nanoplatform by assembling polyetherimide (PEI), indocyanine green (ICG), and multivalent DNAzymes for reversing thermoresistance in PTT. The nanoplatform presented great gene silencing ability and excellent performance in photothermal conversion, which would sensitize MCF-7 cells to hyperthermia by downregulating the overexpression of HSP70 101 (Fig.…”

Reconstituting Low‐Density Lipoprotein with NIR‐Absorbing Organic Photothermal Agents for Targeted Killing of Cancer Cells

“…[1][2][3] To achieve efficient heat generation and deep light penetration, the development of photothermal systems with high photothermal conversion efficiencies (PCEs) and strong absorption in the near-infrared (NIR) region is typically required. [4][5][6][7] At present, a number of PTT systems with diverse nanostructures have been developed; [8][9][10][11][12] however, these PTT systems do not possess intrinsic tumor-targeting capability, leading to DOI: 10.1002/marc.202300395 indiscriminate thermal damage to both cancer and normal cells. [13][14][15] Although tumortargeting moieties or exogenous tumortargeting nanocarriers have been employed to address the aforementioned issue, [16][17][18][19] these strategies either suffer from complicated chemical modification and/or introduce undesired immunogenicity to biological systems.…”