Aptamer-Targeted Gold-Modified Porous Silicon Nanoparticles for Enhanced Photothermal Cancer Therapy

Background/Objectives: A key challenge in nanoparticle-mediated photothermal therapy is to combine efficient light-to-heat conversion with selective recognition of tumor cells. Here, we developed Gli233 aptamer-functionalized gold-modified porous silicon nanoparticles (Apt-Au-pSi NPs) as a targeted hybrid photothermal platform for glioma treatment. Methods: Small Au nanocrystals were generated directly within preformed porous silicon nanoparticles by ultrasound-assisted treatment in the presence of HAuCl4, followed by surface functionalization with the aptamer. The photothermal response was evaluated under 660 nm irradiation, while cytotoxicity, nanoparticle–cell interactions, and photothermal cell death were assessed in a patient-derived human glioma culture using non-functionalized and scrambled-oligonucleotide-functionalized particles as controls. Results: Porous silicon itself contributed to light-to-heat conversion, whereas incorporation of Au substantially enhanced photothermal heating. Apt-Au-pSi NPs showed low intrinsic cytotoxicity, promoted significantly stronger nanoparticle–cell interactions, and produced greater photothermal cell death than both Au-pSi NPs and scrambled-control particles. In an exploratory orthotopic mouse glioma model, Apt-Au-pSi NPs produced greater cranial-surface heating during irradiation and were associated with a qualitative reduction in MRI contrast enhancement and more pronounced histopathological alterations than the scrambled control. Conclusions: These findings indicate that integrating the intrinsic photothermal contribution of porous silicon, plasmonic Au nanostructures, and Gli233-mediated molecular recognition within a single nanoparticle platform may enhance the biological effectiveness and selectivity of photothermal treatment in the tested glioma model.