Biomaterial-Based CRISPR/Cas9 Delivery Systems for Tumor Treatment.

CRISPR/Cas9 gene editing technology is characterized by high specificity and efficiency, and has been applied to the treatment of human diseases, especially tumors involving multiple genetic modifications. However, the clinical application of CRISPR/Cas9 still faces some major challenges, the most urgent of which is the development of optimized delivery vectors. Biomaterials are currently the best choice for use in CRISPR/Cas9 delivery vectors owing to their tunability, biocompatibility, and efficiency. As research on biomaterial vectors continues to progress, hope for the application of the CRISPR/Cas9 system for clinical oncology therapy builds. In this review, we first detail the CRISPR/Cas9 system and its potential applications in tumor therapy. Then, we introduce the different delivery forms and compare the physical, viral, and non-viral vectors. In addition, we analyze the characteristics of different types of biomaterial vectors. We further review recent research progress in the use of biomaterials as vectors for CRISPR/Cas9 delivery to treat specific tumors. Finally, we summarize the shortcomings and prospects of biomaterial-based CRISPR/Cas9 delivery systems.

Flourishing tumor organoids: History, emerging technology, and application.

Malignant tumors are one of the leading causes of death which impose an increasingly heavy burden on all countries. Therefore, the establishment of research models that closely resemble original tumor characteristics is crucial to further understanding the mechanisms of malignant tumor development, developing safer and more effective drugs, and formulating personalized treatment plans. Recently, organoids have been widely used in tumor research owing to their advantages including preserving the structure, heterogeneity, and cellular functions of the original tumor, together with the ease of manipulation. This review describes the history and characteristics of tumor organoids and the synergistic combination of three-dimensional (3D) culture approaches for tumor organoids with emerging technologies, including tissue-engineered cell scaffolds, microfluidic devices, 3D bioprinting, rotating wall vessels, and clustered regularly interspaced short palindromic repeats-CRISPR-associated protein 9 (CRISPR-Cas9). Additionally, the progress in research and the applications in basic and clinical research of tumor organoid models are summarized. This includes studies of the mechanism of tumor development, drug development and screening, precision medicine, immunotherapy, and simulation of the tumor microenvironment. Finally, the existing shortcomings of tumor organoids and possible future directions are discussed.

Cell membrane-coated nanomaterials for cancer therapy.

With the development of nanotechnology, nanoparticles have emerged as a delivery carrier for tumor drug therapy, which can improve the therapeutic effect by increasing the stability and solubility and prolonging the half-life of drugs. However, nanoparticles are foreign substances for humans, are easily cleared by the immune system, are less targeted to tumors, and may even be toxic to the body. As a natural biological material, cell membranes have unique biological properties, such as good biocompatibility, strong targeting ability, the ability to evade immune surveillance, and high drug-carrying capacity. In this article, we review cell membrane-coated nanoparticles (CMNPs) and their applications to tumor therapy. First, we briefly describe CMNP characteristics and applications. Second, we present the characteristics and advantages of different cell membranes as well as nanoparticles, provide a brief description of the process of CMNPs, discuss the current status of their application to tumor therapy, summarize their shortcomings for use in cancer therapy, and propose future research directions. This review summarizes the research progress on CMNPs in cancer therapy in recent years and assesses remaining problems, providing scholars with new ideas for future research on CMNPs in tumor therapy.

Emerging biomaterials for tumor immunotherapy.

BACKGROUND: The immune system interacts with cancer cells in various intricate ways that can protect the individual from overproliferation of cancer cells; however, these interactions can also lead to malignancy. There has been a dramatic increase in the application of cancer immunotherapy in the last decade. However, low immunogenicity, poor specificity, weak presentation efficiency, and off-target side effects still limit its widespread application. Fortunately, advanced biomaterials effectively contribute immunotherapy and play an important role in cancer treatment, making it a research hotspot in the biomedical field. MAIN BODY: This review discusses immunotherapies and the development of related biomaterials for application in the field. The review first summarizes the various types of tumor immunotherapy applicable in clinical practice as well as their underlying mechanisms. Further, it focuses on the types of biomaterials applied in immunotherapy and related research on metal nanomaterials, silicon nanoparticles, carbon nanotubes, polymer nanoparticles, and cell membrane nanocarriers. Moreover, we introduce the preparation and processing technologies of these biomaterials (liposomes, microspheres, microneedles, and hydrogels) and summarize their mechanisms when applied to tumor immunotherapy. Finally, we discuss future advancements and shortcomings related to the application of biomaterials in tumor immunotherapy. CONCLUSION: Research on biomaterial-based tumor immunotherapy is booming; however, several challenges remain to be overcome to transition from experimental research to clinical application. Biomaterials have been optimized continuously and nanotechnology has achieved continuous progression, ensuring the development of more efficient biomaterials, thereby providing a platform and opportunity for breakthroughs in tumor immunotherapy.

Functional acellular matrix for tissue repair.

In view of their low immunogenicity, biomimetic internal environment, tissue- and organ-like physicochemical properties, and functionalization potential, decellularized extracellular matrix (dECM) materials attract considerable attention and are widely used in tissue engineering. This review describes the composition of extracellular matrices and their role in stem-cell differentiation, discusses the advantages and disadvantages of existing decellularization techniques, and presents methods for the functionalization and characterization of decellularized scaffolds. In addition, we discuss progress in the use of dECMs for cartilage, skin, nerve, and muscle repair and the transplantation or regeneration of different whole organs (e.g., kidneys, liver, uterus, lungs, and heart), summarize the shortcomings of using dECMs for tissue and organ repair after refunctionalization, and examine the corresponding future prospects. Thus, the present review helps to further systematize the application of functionalized dECMs in tissue/organ transplantation and keep researchers up to date on recent progress in dECM usage.

Association of matrix metalloproteinase-9 and nitric oxide with hypertension in obstructive sleep apnea.

Background: Patients with obstructive sleep apnea (OSA) are more likely to suffer from hypertension. At the same time, the serum levels of matrix metalloproteinase-9 (MMP-9) and nitric oxide (NO) in patients with OSA are also changed in OSA patients. We investigated the correlation between serum levels of MMP-9, NO in patients with OSA and their association with hypertension in those patients, and the effects of continuous positive airway pressure therapy (CPAP) on these serum biomarkers and blood pressure. Methods: Serum MMP-9 and NO levels and blood pressure of 57 patients with newly diagnosed OSA and 30 controls were measured; among them, 30 patients with moderate to severe OSA underwent 3-month CPAP treatment. Results: In comparison to the control group, the MMP-9 serum levels were higher (232.8 ± 103.2 ng/ml versus 161.6 ± 56.5 ng/ml, p < .001*), there was no statistical significance difference among serum NO (26.7 ± 9.1 IU/ml versus 31.0 ± 11.7 IU/ml, p = .06), and MMP-9 was negatively correlated to NO, especially in patients with hypertension (r = -.644, p = .02*). MMP-9, NO, and blood pressure were significantly recovered in the patients with OSA after CPAP treatment for 3 months (p < .05*). Conclusion: The MMP-9 level and the NO level were altered in OSA patients. The relationship between the two especially in patients with hypertension suggests the potential mechanism of OSA-induced hypertension.