Rabies Virus-Inspired Silica-Coated Gold Nanorods as a Photothermal Therapeutic Platform for Treating Brain Tumors

Unique rabies virus-mimetic silica-coated gold nanorods (RVG-PEG-AuNRs@SiO₂) to treat brain gliomas were introduced. These gold nanorods (AuNRs) were surface-modified with RVG29, enabling them to bypass the BBB and enter the brain by way of the central nervous system, presumably through the nicotinic AchR. Their rod shape increased their interaction with the nicotinic AchR and increased the localized surface plasmon resonance (LSPR) signal in response to near-infrared (NIR) light in the context of photothermal therapy (PTT). To create rabies virus-like AuNRs, we first synthesized longitudinally grown gold nanorods. HAuCl4 was associated by silver nitrate (AgNO₃) in the presence of a surfactant (cetyltrimethylammonium bromide: CTAB) and a strong reducing agent (sodium borohydride: NaBH₄). The resulting gold seeds were 4.7 ∓ 1.3 nm in size and spherical. To increase the efficiency of longitudinal growth of AuNRs, hydroquinone was added as a reducing agent instead of ascorbic acid, because nanoparticle growth is highly sensitive to the concentration of ascorbic acid added. Next, we induced transverse growth on the AuNRs to reduce their AR to that of RABV. However, because transverse overgrowth of AuNRs can result in partial or complete loss of LSPR around =820 nm due to the low AR, striking a balance between increasing the width and preserving the LSPR is important. Next, we created an outmost material layer on the surface of the AuNRs to synchronize the aspect ratio with rabies virus and mimic the outermost glycoprotein layer on the envelope of rabies virus virions. At the initial stage, an albumin layer between AuNRs body and RVG29 peptide had been designed to more closely mimic the matrix protein (lipoproteins) of RABV. In this regard, a silica material, tetraethyl orthosilicate (TEOS), was coated on the surface of the AuNRs to complete structural mimicry of RABV. As a comparator, spherical AuNPs were fabricated. The results support that the rabies virus mimetic gold nanorods are a potential prototype delivery platform for treating brain tumors.