NIR-responsive porous gold nanorod dispersed in a 3D gelatin scaffold for stimulus-responsive drug release and synergistic therapy

Abstract

Biodegradable porous nanomaterials have emerged as a promising avenue for tumor drug delivery owing to their capacity to encapsulate large quantities of drugs and their compatibility with biological systems. Despite the widespread recognition of gold nanorods for their therapeutic potential, studies on porous gold nanorods remain relatively few. Herein, we synthesized thiol-functionalized porous gold nanorods (PGNRs) that exhibit strong absorbance in the NIR region of light spectrum (750 nm), resulting in excellent photothermal properties with a photothermal conversion efficiency of 79%. Meanwhile, the intrinsic porous structure with a multimodal pore size and large surface area of 261 m² g⁻¹ makes PGNR an ideal material for different drug carriers. A model drug doxorubicin loaded on PGNR with 98.7% encapsulation efficiency exhibits good cationic Au and π interaction and a large surface area. To prevent premature drug release and ensure sustained drug delivery at the target site, we designed gelatin and tannic acid-based thermoresponsive hydrogels capturing PGNR-DOX in the matrix. Upon exposure to an NIR laser of 750 nm wavelength, the temperature of this hydrogel increased beyond the upper critical solution temperature (42 °C), leading to a gel-to-sol phase transition that enhances PGNR-DOX release at the specific site. This NIR-triggered hyperthermia facilitates tumor penetration, and the drug conjugate quickly dissociated in an intrinsic acidic environment due to weak cation–π interaction. The effects of phototherapy and chemotherapy together are demonstrated through in vitro experiments. Therefore, this NIR light-responsive nanoplatform holds promising properties and can be considered an ideal material for in vivo studies.