# Synthesis of Hydrogel-Based Microgels and Nanogels Toward Therapeutic and Biomedical Applications
## 5 Therapeutic and Biomedical Applications of Micro- and Nano-Hydrogels
### Anticancer Treatment
The resulting hydrogel encapsulated DNA/doxorubicin complexes and demonstrated sustained release over 40 days, which showed suppressed tumor recurrence and metastasis and confirmed immunogenic cell death and a damage-associated molecular pattern, while achieving an 80% survival rate over 60 days in preclinical models. The MGC hydrogel also promoted cytotoxic T lymphocyte infiltration, directly affecting the tumor microenvironment (TME) [11]. [PERSON] et al. developed a poly(N-isopropylacrylamide-co-acrylic acid)/Prussian blue (PNA@PB) microgel system for synergistic photothermal chemotherapy. This composite microgel leveraged NIR light to induce photothermal effects and enabled controlled drug release and tumor ablation. Prussian blue served as photothermal agent to raise the system temperature above the LCST of the copolymer upon irradiation of an 808 nm NIR laser, causing the volumetric contraction of the microgel and release of DOX. The resulting microgel showed 51% drug encapsulation efficiency and a controlled release of 36% under NIR. Effective tumor cell apoptosis was confirmed in vitro, while in vivo tests showed tumor growth suppression in a xenograft mouse model [207]. Figure 6: Applications of micro- and nanogels in anticancer treatment. (**a**) Nanoscale hydrogels served as an effective drug carrier that can selectively accumulate within the tumor. (**b**) More conventional approach taken using the macroscale hydrogel incorporated with a chemotherapeutic drug, demonstrating sustained release of the drug. (”_p_ < 0.05, \"\"_p_ < 0.01, \"\"_p_ < 0.001). Reproduced with permission from [207]. Licensed under CC BY 4.0, adapted from [11]. [PERSON] et al. developed a photothermal-responsive, injective hydrogel by combining chitosan-capped gold nanoparticles and Olaparib-liposomes for enhanced antitumor therapy. Through an approach combining mild photothermal activity and inhibiting tumor DNA damage repair, this hydrogel demonstrated in vivo suppression of breast tumor growth, localized tumor ablation, and reactive oxygen species (ROS) generation [70]. [PERSON] et al. demonstrated a zwitterionic hydrogel system designed for post-operative breast cancer treatment by utilizing a macrophage membrane and STING agonist. The zwitterionic component helped to reduce protein adsorption and immune recognition, while ensuring stability and reduced off-target effects of the hydrogel system. This hydrogel system incorporates macrophage membrane-coated nanoparticles and 2\({}^{\prime}\),3\({}^{\prime}\)-cGAMP to achieve tumor-targeted drug delivery and TME remodeling. They reported the controlled release of DOX, triggered by the acidic TME, DNA damage-induced immunogenic cell death, and enhanced CD8\({}^{+}\) T cell filtration as confirmed in in vivo studies [102]. While the applications described above are considered a direct anticancer therapy, hydrogel plays an imperative role in supportive anticancer technology, such as gel dosimetry [47; 255]. Fricke gel dosimeters, hydrogel matrices composed of ferrous ions (Fe\({}^{2+}\)), experience radiation-induced oxidation to ferric ions (Fe\({}^{3+}\)) that allows the quantification of spatial dose distributions both in vivo and in vitro [47; 256]. In these applications, hydrogels such as PVA or gelatin help to stabilize radicals and provide tissue-like properties, which are indispensable features for validating and optimizing radiation delivery in stereotactic radiotherapy and proton therapy. Gel dosimetry, as a supportive anticancer therapy, directly impacts the overall efficacy of radiotherapy, ultimately enhancing the survival rate of patients. Accurate dose measurement and 3D mapping ensure that high doses are delivered to the target sites while minimally damaging the surrounding healthy tissues [47; 257].