Silica-Coated Gold Nanorod-Incorporated Injectable Hydrogels for Photothermally-Modulated Localized Drug Delivery

Polymeric hydrogels are a versatile platform for effective therapeutic delivery, especially for cancer therapy due to their tunable physicochemical properties and ability to respond to external stimuli. Incorporation of nanomaterials as photothermal agents further enhances their potential for effective therapeutic delivery. In this study, an injectable in situ hydrogel was developed from pH-responsive poly(acrylic acid) (PAA) and thermoresponsive PF127 framework, encapsulating photothermal modality silica-coated gold nanorods (SNRs) and anticancer drugs paclitaxel (PTX) and methotrexate (MTX). The PAA–PF127 hydrogel possessed injectable characteristics and demonstrated rapid gelation in around 5 min at physiological temperature (37 °C) and tumor acidic pH (∼5.5), ascertaining its potential for intratumoral injections. Further, injectability, rapid gelation, and spatial distribution within chicken breast tissue confirmed the sol–gel transition of the hydrogel required for localized drug depot and tissue delivery, as well as photothermal responsiveness, especially in the tumor environment. The PAA–PF127-SNRs-PTX hydrogel and PAA–PF127-SNRs-MTX hydrogel exhibited photothermally modulated drug release as a function of hydrogel volume, concentration of SNRs, and near-infrared (NIR) irradiation dosage. Biocompatibility tests revealed appreciable MCF-7 cell viability of the PAA–PF127 hydrogel framework (∼80%) after 24 h. Loading of photothermal and chemotherapeutic agents improved the therapeutic efficacy on the MCF-7 cell line upon NIR irradiation. At an irradiation intensity of 0.75 W/cm 2 for 40 min, cancer cell viability declined to ∼10% for both PTX and MTX-loaded hydrogels in vitro. Overall, the synthesized hydrogel platform demonstrates noteworthy potential for anticancer photochemotherapy and stimuli-responsive localized therapeutic delivery with minimal toxicity to healthy tissue.