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

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.