Facile Alkyne Assembly-Enabled Functional Au Nanosheets for Photoacoustic Imaging-Guided Photothermal/Gene Therapy of Orthotopic Glioblastoma.

in Journal of the American Chemical Society by Xixi Hu, Peiling Li, Dongdong Xu, Hua Liu, Qiaoqiao Hao, Mengyang Zhang, Zhaoyin Wang, Tianxiang Wei, Zhihui Dai

TLDR

  • The study creates a special kind of tiny metal sheets called AuNSs and adds a special kind of peptide called RGD to them. The AuNSs are also given a special kind of RNA called siRNA. The AuNSs and RGD work together to target the blood-brain barrier (BBB) and tumor regions in the brain. The study uses a special kind of imaging called photoacoustic imaging to guide the therapy. The study shows that the AuNSs-RGD-C≡C-siRNA (ARCR) is effective in treating glioblastoma (GBM).

Abstract

Treatment of glioblastoma (GBM) remains challenging due to the presence of blood-brain barrier (BBB) and tumor heterogeneity. Herein, Au nanosheets (AuNSs) functionalized with RGD peptides and small interfering RNA (siRNA), referred to as AuNSs-RGD-C≡C-siRNA (ARCR), are prepared to achieve multimodal therapy for GBM. The AuNSs with a large modifiable surface area, intriguing photothermal conversion efficiency (50.26%), and remarkable photothermal stability (44 cycles over 7 h) are created using a well-designed amphiphilic surfactant. Furthermore, alkynyl groups are assembled onto the Au surface within 1 min, enabling strong covalent binding of siRNA to AuNSs and thereby avoiding the interference from biological thiols. Owing to the lipophilicity of the surfactant and the targeting property of RGD, ARCR effectively passes through the BBB and accumulates in GBM tumor regions, allowing near-infrared photoacoustic imaging-guided photothermal/gene therapy. This work proposes a facile strategy to construct theranostic Au-based materials, highlighting the potential of multifunctional nanoagents for GBM therapy.

Overview

  • The study aims to develop a multimodal therapy for glioblastoma (GBM) using Au nanosheets (AuNSs) functionalized with RGD peptides and small interfering RNA (siRNA).
  • The methodology involves preparing AuNSs with a large modifiable surface area, photothermal conversion efficiency, and photothermal stability. Alkynyl groups are assembled onto the Au surface to enable strong covalent binding of siRNA to AuNSs. The RGD peptide is used for targeting the blood-brain barrier (BBB) and tumor regions. The study utilizes near-infrared photoacoustic imaging-guided photothermal/gene therapy.

Comparative Analysis & Findings

  • The study demonstrates the successful preparation of AuNSs-RGD-C≡C-siRNA (ARCR) with high photothermal conversion efficiency and photothermal stability. The ARCR effectively passes through the BBB and accumulates in GBM tumor regions, allowing near-infrared photoacoustic imaging-guided photothermal/gene therapy.

Implications and Future Directions

  • The study highlights the potential of multifunctional nanoagents for GBM therapy. Future research should focus on improving the efficiency of gene delivery and optimizing the photothermal conversion efficiency of ARCR. Additionally, the study suggests the use of ARCR for other brain tumors and as a diagnostic tool for GBM.
Read Full Article