Functionalized Graphene Oxide Nanostructures Enhance Targeted Drug and Gene Delivery, Immunomodulation, Photothermal/Photodynamic Therapy, and Cancer Theranostics

<b><i>Background:</i></b> Graphene oxide (GO), a multifunctional two-dimensional nanomaterial, has gained significant attention in oncology due to its large surface area, tunable surface chemistry, and excellent biocompatibility. These properties enable innovative strategies for cancer treatment and detection. <b><i>Objective:</i></b> This review aims to summarize the diverse biomedical applications of GO, focusing on its role in targeted drug and gene delivery, immunomodulation, photothermal and photodynamic therapy, and theranostic approaches. <b><i>Methods:</i></b> Recent preclinical studies and reports on GO-based nanostructures were critically analyzed to explore their physicochemical characteristics, functionalization strategies, and therapeutic performance. The review also evaluates translational aspects by assessing pharmacokinetics, toxicity, and regulatory considerations related to GO systems. <b><i>Results:</i></b> GO exhibits abundant oxygen-rich functional groups such as hydroxyl and carboxyl, facilitating high drug-loading efficiency and controlled release through pH- and redox-sensitive mechanisms. These properties enhance tumor-targeted drug delivery and minimize systemic toxicity. GO's photothermal conversion ability supports near-infrared-triggered therapy, achieving tumor size reductions up to 80% in preclinical models using photosensitizers like chlorin e6. Moreover, GO-based nanoplatforms augment cancer immunotherapy by modulating immune signaling, promoting antigen presentation, and stimulating cytokine secretion. Despite these advantages, clinical translation is limited by challenges such as dose-dependent cytotoxicity, hemocompatibility, uncertain biodegradation, and lack of standardized synthesis. Variations in particle size, oxidation level, and surface functionalization lead to inconsistent biological outcomes, impeding regulatory approval and clinical progress. <b><i>Conclusion:</i></b> Theranostic platforms combining GO with agents such as doxorubicin and indocyanine green enable integrated chemotherapy, phototherapy, and imaging functionalities. Optimization of GO synthesis, surface modification, and large-scale production could enhance its safety and clinical viability. This review presents a multidisciplinary framework connecting GO nanomaterial design with translational oncology and categorizes GO-based hybrids such as GO polymer conjugates and metal nanocomposites to guide future design, mechanism elucidation, and clinical translation.