Graphene-based nanomaterials (GBNs) have been the subject of research focus in the scientific community because of their excellent physical, chemical, electrical, mechanical, thermal, and optical properties. Several studies have been conducted on GBNs, and they have provided a detailed review and summary of various applications. However, comprehensive comments on biomedical applications and potential risks and strategies to reduce toxicity are limited. In this review, we systematically summarized the following aspects of GBNs in order to fill the gaps: (1) the history, synthesis methods, structural characteristics, and surface modification; (2) the latest advances in biomedical applications (including drug/gene delivery, biosensors, bioimaging, tissue engineering, phototherapy, and antibacterial activity); and (3) biocompatibility, potential risks (toxicity in vivo/vitro and effects on human health and the environment), and strategies to reduce toxicity. Moreover, we have analyzed the challenges to be overcome in order to enhance application of GBNs in the biomedical field.

Malignant tumors are life-threatening, and chemotherapy is one of the common treatment methods. However, there are often many factors that contribute to the failure of chemotherapy. The multidrug resistance of cancer cells during chemotherapy has been reported, since tumor cells’ sensitivity decreases over time. To overcome these problems, extensive studies have been conducted to reverse drug resistance in tumor cells. Elemene, an extract of the natural drug Curcuma wenyujin, has been found to reverse drug resistance and sensitize cancer cells to chemotherapy. Mechanisms by which elemene reverses tumor resistance include inhibiting the efflux of ATP binding cassette subfamily B member 1(ABCB1) transporter, reducing the transmission of exosomes, inducing apoptosis and autophagy, regulating the expression of key genes and proteins in various signaling pathways, blocking the cell cycle, inhibiting stemness, epithelial–mesenchymal transition, and so on. In this paper, the mechanisms of elemene’s reversal of drug resistance are comprehensively reviewed.

Introduction of exogenous genes into target cells to overcome various tumor diseases caused by genetic defects or abnormalities and gene therapy, a new treatment method, provides a promising strategy for tumor treatment. Over the past decade, gene therapy has made exciting progress; however, it still faces the challenge of low nucleic acid delivery and release efficiencies. The emergence of nonviral vectors, primarily nanodelivery and release systems (NDRS), has resulted in a historic breakthrough in the application of gene therapy. NDRS, especially stimulus-responsive NDRS that can respond in a timely manner to changes in the internal and external microenvironment (eg, low pH, high concentration of glutathione/reactive oxygen species, overexpressed enzymes, temperature, light, ultrasound, and magnetic field), has shown excellent loading and release advantages in the precision and efficiency of tumor gene therapy and has been widely applied. The only disadvantage is that poor transfection efficiency limits the in-depth application of gene therapy in clinical practice, owing to the presence of biological barriers in the body. Therefore, this review first introduces the development history of gene therapy, the current obstacles faced by gene delivery, strategies to overcome these obstacles, and conventional vectors, and then focuses on the latest research progress in various stimulus-responsive NDRS for improving gene delivery efficiency. Finally, the future challenges and prospects that stimulus-responsive NDRS may face in clinical application and transformation are discussed to provide references for enhancing in-depth research on tumor gene therapy.

Objective: Acute lung injury (ALI) features uncontrolled pulmonary inflammation and excessive reactive oxygen species (ROS), lacking effective targeted therapies. Hesperetin (HST) has anti-inflammatory and antioxidant effects, but poor solubility and weak lesion targeting limit its application. Herein, based on the characteristics of ALI lesion stromal cell-derived factor-1α (SDF-1α) and ROS overexpression, the authors constructed ROS-sensitive oxy-hydroxypropyl-β-cyclodextrin (Oxi-Hp-β-CD) and CXCR4-modified biomimetic nanoparticles (CXCR4-HST@BNPs) to achieve targeted (CXCR4/SDF-1α axis) and ROS-triggered HST delivery for the treatment of ALI. Methods: MLE-12 cells with overexpressed CXCR4 were constructed by lentiviral transduction and the cell membranes were extracted for encapsulating nanoparticles loaded with HST. Physicochemical properties, drug release profile, cellular uptake and in vivo distribution were characterized, and therapeutic efficacy and mechanisms were assessed using LPS-induced cellular and murine ALI models. Results: Prepared CXCR4-HST@BNPs possessed uniform particle size, high encapsulation efficiency and obvious ROS-dependent drug release. Benefiting from CXCR4/SDF-1α-mediated active targeting, the nanoparticles selectively accumulated in inflamed lung tissue with favorable acute biocompatibility. In vitro and in vivo experiments confirmed that CXCR4-HST@BNPs significantly alleviated pulmonary edema, suppressed pro-inflammatory cytokine overexpression and alleviated inflammatory injury. Mechanistically, the formulation eliminated excessive intracellular ROS, restored mitochondrial membrane potential and raised cellular ATP levels. Conclusion: In conclusion, CXCR4-HST@BNPs effectively ameliorate ALI via anti-oxidation and mitochondrial protection, representing a prospective ALI-targeted nanotherapeutic candidate.