Macrophage-evading and tumor-specific apoptosis inducing nanoparticles for targeted cancer therapy

Extended circulation of anticancer nanodrugs in blood stream is essential for their clinical applications. However, administered nanoparticles are rapidly sequestered and cleared by cells of the mononuclear phagocyte system (MPS). In this study, we developed a biomimetic nanosystem that is able to efficiently escape MPS and target tumor tissues. The fabricated nanoparticles (TM-CQ/NPs) were coated with fibroblast cell membrane expressing tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL). Coating with this functionalized membrane reduced the endocytosis of nanoparticles by macrophages, but increased the nanoparticle uptake in tumor cells. Importantly, this membrane coating specifically induced tumor cell apoptosis via the interaction of TRAIL and its cognate death receptors. Meanwhile, the encapsulated chloroquine (CQ) further suppressed the uptake of nanoparticles by macrophages, and synergized with TRAIL to induce tumor cell apoptosis. The vigorous antitumor efficacy in two mice tumor models confirmed our nanosystem was an effective approach to address the MPS challenge for cancer therapy. Together, our TM-CQ/NPs nanosystem provides a feasible approach to precisely target tumor tissues and improve anticancer efficacy.

Advances in modification and delivery of nucleic acid drugs / 浙江大学学报·医学版

Nucleic acid-based drugs, such as RNA and DNA drugs, exert their effects at the genetic level. Currently, widely utilized nucleic acid-based drugs include nucleic acid aptamers, antisense oligonucleotides, mRNA, miRNA, siRNA and saRNA. However, these drugs frequently encounter challenges during clinical application, such as poor stability, weak targeting specificity, and difficulties in traversing physiological barriers. By employing chemical modifications of nucleic acid structures, it is possible to enhance the stability and targeting specificity of certain nucleic acid drugs within the body, thereby improving delivery efficiency and reducing immunogenicity. Moreover, utilizing nucleic acid drug carriers can facilitate the transportation of drugs to lesion sites, thereby aiding efficient intracellular escape and promoting drug efficacy within the body. Currently, commonly employed delivery carriers include virus vectors, lipid nanoparticles, polymer nanoparticles, inorganic nanoparticles, protein carriers and extracellular vesicles. Nevertheless, individual modifications or delivery carriers alone are insufficient to overcome numerous obstacles. The integration of nucleic acid chemical modifications with drug delivery systems holds promise for achieving enhanced therapeutic effects. However, this approach also presents increased technical complexity and clinical translation costs. Therefore, the development of nucleic acid drug carriers and nucleic acid chemical modifications that are both practical and simple, while maintaining high efficacy, low toxicity, and precise nucleic acid delivery, has become a prominent research focus in the field of nucleic acid drug development. This review comprehensively summarizes the advancements in nucleic acid-based drug modifica-tions and delivery systems. Additionally, strategies to enhance nucleic acid drug delivery efficiency are discussed, with the aim of providing valuable insights for the translational application of nucleic acid drugs.

Effect of Xiaoyuhuatan decoction on insulin resistance of nonalchoholic fatty liver disease rat / 中国基层医药

Objective By observing the effect of Xiaoyuhuatan decoction on insulin resistance in rar with nonalchoholic fatty liver,the author made a reasearch into this herb'S machanism on cambating on nonalchoholic fatty liver.Methods The insulin resistance rat model was fed by high fat forage and Dongbaogantai control group was set up for the sake of comparion.We determined the contents of total cholesterol(TC),triglyceride(TG),free fatty acid(FFA),fasting plasma glucose(FBG),fasting serum insulin(INS)in serum and the contents of TC,TG of liver tissue homogenate of each group,and the degree of hepatocytic steatosis.Results Xiaoyuhuatan decoction could obviously decrease the index of insulin resistance and improve insulin insensitive index.Lipid in blood serum and hepatic tissues were significantly decreased,liver fat cell denaturation was improved.Conclusion The thrapentic eftect of Xiaoyuhuatan Decoction on fatty liver is probably contribute tO this herb's mechanism of improving insulin resistance and increasing insulin insensitive.