Near-infrared responsive, mesoporous silica nanoparticle-incorporated injectable hydrogels for on-demand anticancer drug delivery applications.

Improving payload encapsulation stability while enabling controlled drug release remains a significant challenge in drug delivery systems. This study develops novel composite hyaluronic acid (HA) hydrogels integrated with NIR-responsive mesoporous silica nanoparticles (MSNPP) to facilitate on-demand delivery of anticancer drugs. MSNPs are coated with thermoresponsive poly (N-acryloyl glycinamide-co-methacrylic acid) (poly(NAGA-co-MAA)) to inhibit drug leakage. The indocyanine green (ICG) and methotrexate (MTX)-loaded nanoparticles are subsequently mixed with biocompatible norbornene-functionalized HA, which is cross-linked using diselenide-tetrazine PEG (PEG-DSe-Tz). This process utilizes an inverse electron-demand Diels-Alder reaction to create injectable nanocomposite hydrogels, providing a minimally invasive delivery platform. Upon NIR laser excitation, the composite hydrogels rapidly accelerate MTX release from MSNPP, likely due to light-triggered de-cross-linking and photothermal effects. These findings highlight the ability of the nanocomposite hydrogels to simultaneously prevent premature payload leakage and enable NIR-responsive drug release. The composite hydrogels exhibit improved mechanical strength, notable porosity, and high drug loading capacity (>90 %). In vitro antitumor analysis confirms the enhanced antitumor activity of the composite hydrogel against HT-29 cell lines. The NIR-responsive MSNPP embedded in the injectable HA hydrogel present a promising candidate for on-demand anticancer drug delivery applications, potentially improving therapeutic efficacy while minimizing side effects.