Medical review (Berlin, Germany)最新文献

The complexity of the tumor microenvironment (TME) severely hinders the therapeutic effects of various cancer treatment modalities. The TME differs from normal tissues owing to the presence of hypoxia, low pH, and immune-suppressive characteristics. Modulation of the TME to reverse tumor growth equilibrium is considered an effective way to treat tumors. Recently, polymeric nanomedicines have been widely used in cancer therapy, because their synthesis can be controlled and they are highly modifiable, and have demonstrated great potential to remodel the TME. In this review, we outline the application of various stimuli responsive polymeric nanomedicines to modulate the TME, aiming to provide insights for the design of the next generation of polymeric nanomedicines and promote the development of polymeric nanomedicines for cancer therapy.

Ferritin is an endogenous protein which is self-assembled by 24 subunits into a highly uniform nanocage structure. Due to the drug-encapsulating ability in the hollow inner cavity and abundant modification sites on the outer surface, ferritin nanocage has been demonstrated great potential to become a multi-functional nanomedicine platform. Its good biocompatibility, low toxicity and immunogenicity, intrinsic tumor-targeting ability, high stability, low cost and massive production, together make ferritin nanocage stand out from other nanocarriers. In this review, we summarized ferritin-based nanomedicine in field of disease diagnosis, treatment and prevention. The different types of drugs to be loaded in ferritin, as well as drug-loading methods were classified. The strategies for site-specific and non-specific functional modification of ferritin were investigated, then the application of ferritin for disease imaging, drug delivery and vaccine development were discussed. Finally, the challenges restricting the clinical translation of ferritin-based nanomedicines were analyzed.

Single-nucleotide variants account for about half of known pathogenic genetic variants in human. Genome editing strategies by reversing pathogenic point mutations with minimum side effects have great therapeutic potential and are now being actively pursued. The emerge of precise and efficient genome editing strategies such as base editing and prime editing provide powerful tools for nucleotide conversion without inducing double-stranded DNA breaks (DSBs), which have shown great potential for curing genetic disorders. A diverse toolkit of base editors has been developed to improve the editing efficiency and accuracy in different context of application. Here, we summarized the evolving of base editors (BEs), their limitations and future perspective of base editing-based therapeutic strategies.

Diabetes is one of the fastest-growing non-communicable diseases, becoming an important public health concern worldwide as well as in China. Currently, China has the largest population living with diabetes. Artificial intelligence (AI) is a fast-growing field and its applications to diabetes could enable the delivery of better management services for people with diabetes. This perspective summarized the latest findings of digital technologies and AI use in the following areas of diabetes care, mainly including screening and risk predictions of diabetes and diabetic complications, precise monitoring and intervention combined with new technologies, and mobile health application in self-management support for people with diabetes. Challenges to promote further use of AI in diabetes care included data standardization and integration, performance of AI-based medical devices, motivation of patients, and sensitivity to privacy. In summary, although the AI applications in clinical practice is still at an early stage, we are moving toward a new paradigm for diabetes care with the rapid development and emerging application of AI.

Immune checkpoint inhibitors (ICIs) like programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitor have shown considerable efficacy in several important cancers including primary liver cancer (PLC) like hepatocellular carcinoma and cholangiocarcinoma. However, only some patients with PLC will benefit, so combination therapy and biomarker classification detected by next-generation sequencing or immunohistochemistry are very important. Herein, we briefly summarize ICI-based therapies and stratify these evolving therapies for advanced PLC into three stages of immunotherapies Mark (Mk.) 1.0, 2.0, and 3.0. We illustrated the significance of ICI monotherapy (Mk. 1.0), offering combinational approaches with traditional strategies (Mk. 2.0) and additional locoregional therapy (Mk. 3.0) to achieve longer survival and even meet the "No Evidence of Disease" status. We also highlight the importance of biomarkers and prognostic factors for patients with advanced PLC treated with ICI-based therapies. Multidisciplinary team management should be investigated and collaborated closely to manage adverse events and sequential therapy suggestions for patients.

Antibodies, as one of the most important components of host adaptive immune system, play an important role in defense of infectious disease, immune surveillance, and autoimmune disease. Due to the development of recombinant antibody technology, antibody therapeutics become the largest and rapidly expanding drug to provide major health benefits to patients, especially for the treatment of cancer patients. Many antibody-based therapeutic strategies have been developed including monoclonal antibodies, antibody-drug conjugates, bispecific and trispecific antibodies and pro-antibodies with promising results from both clinical and pre-clinical trials. However, the response rate and side-effect still vary between patients with undefined mechanisms. Here, we summarized the current and future perspectives of antibody-based cancer immunotherapeutic strategies for designing next-generation drugs.