The role of protein corona on nanodrugs for organ-targeting and its prospects of application.

Nowadays, nanodrugs become a hotspot in the high-end medical field. They have the ability to deliver drugs to reach their destination more effectively due to their unique properties and flexible functionalization. However, the fate of nanodrugs in vivo is not the same as those presented in vitro, which indeed influenced their therapeutic efficacy in vivo. When entering the biological organism, nanodrugs will first come into contact with biological fluids and then be covered by some biomacromolecules, especially proteins. The proteins adsorbed on the surface of nanodrugs are known as protein corona (PC), which causes the loss of prospective organ-targeting abilities. Fortunately, the reasonable utilization of PC may determine the organ-targeting efficiency of systemically administered nanodrugs based on the diverse expression of receptors on cells in different organs. In addition, the nanodrugs for local administration targeting diverse lesion sites will also form unique PC, which plays an important role in the therapeutic effect of nanodrugs. This article introduced the formation of PC on the surface of nanodrugs and summarized the recent studies about the roles of diversified proteins adsorbed on nanodrugs and relevant protein for organ-targeting receptor through different administration pathways, which may deepen our understanding of the role that PC played on organ-targeting and improve the therapeutic efficacy of nanodrugs to promote their clinical translation.

Targeting Cul3-scaffold E3 ligase complex via KLHL substrate adaptors for cancer therapy.

Targeted therapy has become increasingly important and indispensable in cancer therapy. Cullin3-RING ligases (CRL3) serve as essential executors for regulating protein homeostasis in cancer development, highlighting that CRL3 might be promising targets in various cancer treatment. However, how to design new targeted therapies by disrupting the function of CRL3 is poorly understood. Here, we focus on the substrate adaptors of CRL3, and carry out a systematical research on the function of Kelch-like (KLHL) family proteins. We have identified twenty-four KLHL proteins with function of tumor promotion and thirteen KLHL proteins with high clinical significance on cancer therapy. Furthermore, we have clarified the novel biological function of KLHL13 as a vital factor that contributes to malignant progression in lung cancer. Taken together, our findings reveal multiple potential therapeutical targets and provide evidence for targeting CRL3 via KLHL substrate adaptors for cancer therapy.

Pharmaceutical strategies for endoplasmic reticulum-targeting and their prospects of application.

Modern drug delivery system (DDS) exerts its unique superiority as to enhancing drug efficacy while reducing their toxicity, which relies heavily on an accurate route of delivery. Based on the fact that most drugs have their own specific target of action, increasing attention is paid to developing strategies for targeting certain tissues, cell lines, and even intracellular structures. Endoplasmic reticulum (ER) is a dynamic and versatile subcellular organelle that participates in multiple physiological and biochemical processes, supporting the survival and homeostasis-maintenance of cells. Genetic or environmental damages may induce ER stress, which is closely coupled to the occurrence and development of many human diseases and even cancers. In this review, recent progress in strategies of direct ER-targeting with specific molecules or carriers are summarized. We also discuss several advances in fields of indirect ER-targeting. This work may provide a deeper understanding over the ER biology and boost the development of precise intracellular regulation, displaying broad prospects of application.