Novel gold nanoparticles targeting somatostatin receptor subtype two with near-infrared light for neuroendocrine tumour therapy

Neuroendocrine tumours (NETs) are rare cancers with positive somatostatin receptor 2 (SSTR2) expression, and treatment strategies for NETs are not satisfactory. Nanomaterial-mediated therapy targeting SSTR2 in NETs is very promising. This study firstly combined mesoporous silica-coated gold nanorods (AuNRs@mSiO₂) and targeting-SSTR2 dodecane tetraacetic acid-tyrosine³-octreotate (DOTA-TATE) into AuNRs@mSiO₂@DOTA-TATE to investigate NETs inhibition under near-infrared light. AuNRs@mSiO₂@DOTA-TATE showed good photothermal conversion efficiency. In vitro, under light irradiation, the cell viability significantly decreased with increasing AuNR@mSiO₂@DOTA-TATE concentration; in two successfully established neuroendocrine tumour organoids with SSTR2 expression, AuNRs@mSiO₂@DOTA-TATE with light inhibited tumours significantly better than AuNRs@mSiO₂ with light. In vivo, the SSTR2-targeting ability and biodistribution of AuNRs@mSiO₂@DOTA-TATE were confirmed with AuNRs@mSiO₂@⁶⁴Cu-DOTA-TATE under micro-positron emission tomography/computed tomography (micro-PET/CT); in the AuNRs@mSiO₂@DOTA-TATE with laser group, the tumour surface temperature increased rapidly, with tumour volumes similar to those in the octreotide group and significantly lower than those in other groups. There was no significant difference in mice body weight between the AuNRs@mSiO₂@DOTA-TATE with laser group and other groups. No significant inflammatory lesions or cell necrosis was found in the main organs. In summary, we presented a feasible strategy to construct AuNRs@mSiO₂@DOTA-TATE with good photothermal conversion efficiency, targeting-SSTR2 ability, significant antitumour effects, and good biocompatibility, warranting further explorations of AuNRs@mSiO₂@DOTA-TATE for NETs therapy applications.