Malignant tumors remain a leading cause of global mortality. Radiotherapy (RT) and immunotherapy are established cornerstone therapies for most solid cancers. Their combination, radio-immunotherapy (IRT), has demonstrated robust synergistic antitumor activity in preclinical models and early-phase clinical trials. However, broader clinical implementation is hindered by intrinsic or acquired radioresistance, systemic toxicities with overlapping organ tropism, and a profoundly immunosuppressive tumor immune microenvironment (TIME). To address these limitations, this review presents a mechanistically integrated framework centered on nanomaterial-enabled strategies: targeted radiosensitization coupled with enhanced immunogenic cell death (ICD); spatiotemporally controlled remodeling of the TIME to counteract immunosuppression; and multifunctional, imaging-guided theranostic platforms for precision IRT delivery and response monitoring. We systematically synthesize recent preclinical advances in nanomaterial-enhanced IRT—including applications across conventional X-ray, proton beam, photothermal, and sonodynamic irradiation—and critically evaluate early-phase clinical data for representative nanotherapeutics (NBTXR3 and AGuIX). Furthermore, we identify and analyze key translational bottlenecks impeding clinical adoption, including scalability, regulatory pathway clarity, and biomarker-driven patient selection. Collectively, this review provides a unified, mechanism-informed foundation to advance rational nanomaterial design and evidence-based clinical translation, thereby strengthening the scientific basis for precision oncology in patients with refractory solid tumors.

Stromal cell-derived factor-1α (SDF-1α) is a potent stem cell recruitment chemokine that can promote angiogenesis, particularly when delivered via gene-activated scaffolds (GAS). This systematic review and meta-analysis synthesized in vitro evidence on the angiogenic potential of SDF-1α GAS. Four databases were utilized to search for eligible studies, comprising investigations that examined the in vitro effects of SDF-1α GAS on angiogenesis-related outcomes compared with gene-free scaffolds. Data on gene expression, protein levels, and endothelial formation were extracted. Meta-analyses were conducted using random or fixed-effect models, expressed as standardized mean difference (SMD) or mean difference (MD) with 95% confidence intervals (CI). Risk of bias was assessed using the Quality Assessment Tool for In Vitro Studies (QUIN) tool. Eight studies were included. Pooled analysis demonstrated SDF-1α GAS efficacy to significantly increase SDF-1α gene expression (SMD = 1.20; 95% CI = 0.13–2.27; p = .03), fold-change of the gene (MD = 12.48; 95% CI = 10.33–14.64; p < .0001), and protein production (MD = 0.29 ng/mL; 95% CI = 0.14–0.43 ng/mL; p = .0001). Most studies showed a moderate risk of bias. Based on in vitro studies, SDF-1α GAS activity is associated with significant elevation of SDF-1α gene expression and protein quantity, although it did not exhibit significant enhancement of VEGF expression or functional endothelial morphogenesis under the studied conditions.

Liposomal nanocarriers are clinically established platforms for targeted drug delivery due to their biocompatibility and ability to encapsulate both hydrophilic and hydrophobic agents. However, conventional single-drug liposomes are limited by suboptimal efficacy, systemic toxicity, and multidrug resistance. Dual-drug-loaded liposomes (DDLs) address these limitations by enabling co-delivery of synergistic agents within a single nanocarrier. This review provides an integrated analysis of DDL systems, focusing on formulation design, drug loading strategies, and key physicochemical parameters governing encapsulation efficiency and controlled release. Mechanistic insights into therapeutic enhancement are highlighted, including modulation of efflux transporters, reversal of epithelial–mesenchymal transition, and synchronized intracellular delivery. The impact of ligand-mediated functionalization on tumor targeting and cellular uptake is also critically evaluated. Unlike existing reviews, this work provides a unified framework integrating formulation design, mechanistic insights into drug synergy, and translational challenges specific to DDLs, addressing a critical gap in the existing literature. Preclinical and clinical evidence, including approved formulations such as Vyxeos, is discussed. Remaining barriers include scale-up, reproducibility, immune interactions, and regulatory complexity. Future directions emphasize personalized and stimulus-responsive nanomedicine for improved cancer therapy.

Artificial intelligence (AI) and gene editing are increasingly being applied to the design and evaluation of mRNA therapeutics. Although mRNA-based medicines have achieved clear clinical impact in vaccination, broader applications remain limited by mRNA instability, delivery barriers, tissue selectivity, and unwanted immunogenicity. This review examines how AI and gene editing can be combined to address these constraints. AI-based models support predictive optimization of untranslated regions, codon usage, secondary structure, and lipid nanoparticle (LNP) formulations, thereby improving the efficiency of sequence and delivery-system design. In parallel, CRISPR-Cas (clustered regularly interspaced short palindromic repeats-associated proteins) systems, base editors, and emerging RNA-editing tools provide platforms for disease modeling, target validation, and functional testing of mRNA-based interventions. We emphasize that the value of this convergence lies in iterative workflows: gene-editing screens generate quantitative datasets for model training, whereas AI helps prioritize editing strategies, guide sequence refinement, and improve delivery design. We also summarize representative applications, translational limitations, and prospects for closed-loop AI-gene editing platforms. Overall, the integration of computational prediction with programmable genome and RNA engineering may support more precise, adaptable, and clinically translatable mRNA therapeutics.

Chronic wounds pose a major clinical challenge due to a complex pathophysiological condition. It is characterized by persistent inflammation, excessive oxidative stress, and a high risk of bacterial infection, which hinders tissue repair. To address this, a multifunctional hydrogel dressing based on gallic acid conjugated chitosan (G-CHI) and integrated with simvastatin and heparin-functionalized Ag/Zn-doped bioactive glass (HBG). The incorporation of gallic acid improved the structural integrity and viscoelastic behavior of the hydrogel. The release kinetics study demonstrated controlled liberation of Ag⁺ and Zn²⁺ ions within biologically safe limits over 24 h, while simvastatin exhibited diffusion-controlled release behavior. The hydrogel also exhibited desirable adhesive properties, indicating its suitability as a wound dressing material. In vitro biofunctional assays showed enhanced antioxidant activity (~75% free radical scavenging), hemocompatibility (< 5% hemolysis), and effectiveness against both Staphylococcus aureus and Escherichia coli (> 90% efficacy in time kill assay). Further, synergistic release of simvastatin and bioglass showed enhanced proliferation of fibroblast (NIH 3T3), keratinocyte (HaCaT), and endothelial cells (SVEC), accompanied by increased collagen deposition compared to control groups. These findings suggest that the synthesized hydrogel (BSG-CHI) provides a favorable microenvironment for tissue regeneration and wound management applications.

Uncontrolled bleeding in wet or actively hemorrhaging environments remains a major clinical challenge in trauma management and surgical procedures. Conventional hemostatic agents and tissue adhesives often exhibit insufficient adhesion strength and delayed coagulation upon contact with blood or moisture at the tissue interface. Inspired by the underwater adhesion mechanism of barnacle cement, we developed an injectable, multifunctional hemostatic adhesive that achieves rapid coagulation, strong adhesion to wet tissues, and inherent antibacterial properties. The adhesive integrates a silicone oil-assisted water-displacement phase with a bioadhesive polymer network composed of carboxymethyl chitosan, hyaluronic acid, and quaternized chitosan. In vitro tests revealed a markedly reduced blood clotting index (9.0% ± 0.6%) and shorter clotting time (2.6 ± 0.5 min), surpassing the performance of commercial gelatin sponges. Enhanced red blood cell adsorption and superior wet tissue adhesion strength (27.3 kPa on porcine skin) compared to fibrin glue further confirm its hemostatic efficacy. The adhesive also demonstrated excellent cytocompatibility and significant antibacterial activity. Overall, this barnacle-inspired injectable adhesive offers a promising approach for achieving rapid hemostasis and infection-resistant wound sealing in moist clinical settings.