摘要
Blocking the programmed death-ligand 1 (PD-L1) on tumor cells with monoclonal antibody therapy has emerged as powerful weapon in cancer immunotherapy. However, only a minority of patients presented immune responses in clinical trials. To develop an alternative treatment method based on immune checkpoint blockade, we designed a novel and efficient CRISPR-Cas9 genome editing system delivered by cationic copolymer aPBAE to downregulate PD-L1 expression on tumor cells specifically knocking out Cyclin-dependent kinase 5 () gene . The expression of PD-L1 on tumor cells was significantly attenuated by knocking out , leading to effective tumor growth inhibition in murine melanoma and lung metastasis suppression in triple-negative breast cancer. Importantly, we demonstrated that aPBAE/Cas9-Cdk5 treatment elicited strong T cell-mediated immune responses in tumor microenvironment that the population of CD8 T cells was significantly increased while regulatory T cells (Tregs) was decreased. It may be the first case to exhibit direct PD-L1 downregulation CRISPR-Cas9 genome editing technology for cancer therapy. It will provide promising strategy for preclinical antitumor treatment through the combination of nanotechnology and genome engineering.
摘要
Artemisinin and its derivatives have shown the potential application value in anti-tumor fields.But their applications are limited due to poor solubility, short half-life and so on;therefore, many scholars devoted themselves to developing and studying relative pharmaceutical preparations.Nano drug delivery system is a new drug delivery tool.Compared with the traditional dosage forms, such as tablets, suppositories and injections, nano drug delivery system has such advantages as good stability, targeted drug release and combined drug delivery.In this review, nano drug delivery carriers for artemisinin were summarized, including nanoparticles, liposomes, micelles, nanomicroemulsions and so on.The research results and characteristics of artemisinin-containing nano formulas in tumor therapy, as well as the co-delivery system of artemisinin and transferrin, were discussed.