Injectable and Natural Humic Acid/Agarose Hybrid Hydrogel for Localized Light-Driven Photothermal Ablation and Chemotherapy of Cancer

Abstract

The injection of theranostic drug-laden hydrogels into subcutaneous tumors has proven to be a promising strategy to achieve precise local tumor eradication. Humic acid, a natural product of biochemical decomposition of animal and plant residues, abundantly exists in soils, peats, oceans, etc. In this study, a robust injectable thermoresponsive agarose hydrogel incorporating sodium humate (SH) and doxorubicin (DOX) was constructed as a unique agent for tumor management based on the combined chemo-photothermal therapeutic effect. SH, which strongly absorbs near-infrared (NIR) light, can efficiently convert light energy into thermal energy, induce local hyperthermia and subsequently trigger sustained drug release from the complex of the SH/DOX@hydrogel through a typical gel–sol transition, resulting in enhanced cellular uptake of therapeutic drugs. Moreover, intratumoral injection of the SH/DOX@hydrogel resulted in a simultaneous chemo-photothermal therapeutic effect against solid tumors under NIR laser irradiation, which may collectively prevent tumor recurrence. In addition, the SH/DOX@hydrogel exhibited ultralow systemic toxicity as demonstrated using an animal model. This work provides a promising attempt to develop a low-cost, light-responsive hydrogel for precise tumor therapy, which may also incorporate extra theranostic modules as an advanced platform for the treatment of cancer or other critical diseases.

How Humic Acids Affect the Rheological and Transport Properties of Hydrogels

“…Several different binding sites in the hydrogel structure were identified. Hou et al [34] prepared an injectable agarose hydrogel incorporating sodium humate and doxorubicin as an agent for tumor management based on the chemo-photo-thermal therapeutic effect.…”

Two-photon polymerization nanolithography technology for fabrication of stimulus-responsive micro/nano-structures for biomedical applications

“…Light, one of the remotely controllable stimuli, has attracted the most research interest for smart materials. In general, light-induced actuation of polymers has two main types: photoisomerization of chromic moieties in a chain of monomers and the photothermal effect of nanoparticles in heat-responsive polymer matrices [110][111][112]. The cis-trans isomerization photoresponse of azobenzene function groups is commonly used in lightresponsive photoresists.…”

Injectable Hydrogels for Cancer Therapy over the Last Decade

“…Agarose (AGR, Figure 18) is an FDA-approved linear polysaccharide derived from marine algae. A robust injectable thermo-responsive AGR hydrogel incorporating sodium humate and DOX was proposed as a valuable tool for chemo-photothermal treatment of breast cancer [258]. Furthermore, DOX@nanoparticles were encapsulated in AGR injectable hydrogels for sustained local drug delivery (Table 9) [259].…”