Research progress on exosome-based antitumor drug delivery system / 中国生物制品学杂志

@#Tumor is the main cause of global related death.Although the existing treatment methods have made significant progress,the lack of specificity and low bioavailability are still the challenge in the treatment.Exosomes are lipid bilayer extracellular vesicles that were released in the range of 30—150 nm when a multi vesicular body(MVB) fuses with plasma membrane,which are important mediators of intercellular communication,and can transport cellular components such as proteins,lipids and nucleic acids to neighboring or distant cells,thus changing the role of recipient cells.Exosomes have been used as natural nano-carriers for drug delivery.After being loaded with antitumor drugs,they can be delivered to the focus for targeted treatment of various tumors,and the therapeutic effect is good.In this paper,the advantages of exosomes-based antitumor drug delivery system,drug loading methods and the research progress of exosomes from different cells in cancer treatment are reviewed so as to provide important basis for the targeted treatment of cancer.

Research progress on exosome-based antitumor drug delivery system / 中国生物制品学杂志

@#Tumor is the main cause of global related death.Although the existing treatment methods have made significant progress,the lack of specificity and low bioavailability are still the challenge in the treatment.Exosomes are lipid bilayer extracellular vesicles that were released in the range of 30—150 nm when a multi vesicular body(MVB) fuses with plasma membrane,which are important mediators of intercellular communication,and can transport cellular components such as proteins,lipids and nucleic acids to neighboring or distant cells,thus changing the role of recipient cells.Exosomes have been used as natural nano-carriers for drug delivery.After being loaded with antitumor drugs,they can be delivered to the focus for targeted treatment of various tumors,and the therapeutic effect is good.In this paper,the advantages of exosomes-based antitumor drug delivery system,drug loading methods and the research progress of exosomes from different cells in cancer treatment are reviewed so as to provide important basis for the targeted treatment of cancer.

Rational development of a human antibody cocktail that deploys multiple functions to confer Pan-SARS-CoVs protection.

Structural principles underlying the composition and synergistic mechanisms of protective monoclonal antibody cocktails are poorly defined. Here, we exploited antibody cooperativity to develop a therapeutic antibody cocktail against SARS-CoV-2. On the basis of our previously identified humanized cross-neutralizing antibody H014, we systematically analyzed a fully human naive antibody library and rationally identified a potent neutralizing antibody partner, P17, which confers effective protection in animal model. Cryo-EM studies dissected the nature of the P17 epitope, which is SARS-CoV-2 specific and distinctly different from that of H014. High-resolution structure of the SARS-CoV-2 spike in complex with H014 and P17, together with functional investigations revealed that in a two-antibody cocktail, synergistic neutralization was achieved by S1 shielding and conformational locking, thereby blocking receptor attachment and viral membrane fusion, conferring high potency as well as robustness against viral mutation escape. Furthermore, cluster analysis identified a hypothetical 3rd antibody partner for further reinforcing the cocktail as pan-SARS-CoVs therapeutics.

Expression of a neurotoxin gene improves the insecticidal activity of Spodoptera litura nucleopolyhedrovirus (SpltNPV).

SpltNPV-C3 is a novel nucleopolyhedrovirus (NPV) screened from 189 wild Spodoptera litura nucleopolyhedrovirus (SpltNPV) clones collected throughout Japan and has high potential insecticidal activity against S. litura. In this study, we constructed two recombinant SpltNPVs, SpltNPV-Δegt and SpltNPV-Δegt-BmK, which were characterized by the disruption of the UDP-glucosyltransferase gene (egt) only and by replacing the egt locus with the Buthus martensi insect-specific toxin gene (BmK ITa1), respectively. The insecticidal activity of these two recombinant viruses was evaluated by 50% lethal time (LT(50)) and 50% lethal concentration (LC(50)) using third instar S. litura larvae. Bioassays showed that the LT(50) of SpltNPV-Δegt was reduced by 25% at a dose of 10(9) Occlusion bodies (OBs)/ml compared to the wild-type SpltNPV. However, the LC(50) values did not change. The SpltNPV-Δegt-BmK reduced LT(50) by 28% at the highest dose of OBs (10(9) OBs/ml) compared to the wild-type SpltNPV, and the LC(50) was nearly an order of magnitude lower than those of the wild-type SpltNPV and SpltNPV-Δegt. However, there was no discernable difference in the LT(50) between SpltNPV-Δegt-BmK and SpltNPV-Δegt when the 3rd instars of S. litura were fed a dose of 10(8) or 10(9) OBs/ml. The results suggest that these two recombinant forms of SpltNPV provide further opportunities to develop these viruses into commercially viable products to control S. litura populations.

[Construction and toxicity the recombinant SpltMNPV expressing the scorpion toxin gene].

OBJECTIVE: To develop a high toxic recombinant Spodoptera litura multicapsid nucleopolyhedroviruse (SpltMNPV) insecticide. METHODS: We constructed a recombinant transfer vector that was characterized by disrupting of ecdysterioid UDP-glucosyltransferase (egt) gene and expressing the mature peptide of the Chinese scorpion, B. martensi Karsch (BmK ITal) gene at the control of ie-1 promoter. The transfer vector and the SpltMNPV II DNA cotransfected the SpLi cells. Recombinant viruses were purified by the end point dilution and fluorescent spot purification. RESULTS: We successfully screened the recombinant SpltMNPV-deltaegt-Pph-egfp-ie-1-BmK ITal of which the egt gene was knocked out and expressed the mature peptide of the BmK ITal gene at the control of ie-1 promoter. Bioassays showed that, compared to the wide-type SpltMNPV, the speed of the recombinant virus killing the S. litura (LT50) increased by 0.7-0.8 days. CONCLUSION: The insecticidal effect of SpltNPV could be increased by inserting the foreign gene, which provided a further opportunity to develop the SpltNPV into commercially viable products to control the S. litura.