Middle East respiratory syndrome coronavirus (MERS-CoV) causes a severe acute respiratory syndrome-like illness with high pathogenicity and mortality due to the lack of effective therapeutics. Currently, only few antiviral agents are available for the treatment of MERS, but their effects have been greatly impaired by low antiviral activity, poor metabolic stability, and serious adverse effects. Therefore, the development of effective treatment for MERS is urgently needed. In this study, a series of heptad repeat 1 (HR1) peptide inhibitors have been developed to inhibit HR1/HR2-mediated membrane fusion between MERS-CoV and host cells, which is the major pathway of MERS-CoV-induced host infections. Particularly, peptide pregnancy-induced hypertension (PIH) exhibits potent inhibitory activity with IC 50 of 1.171 μM, and its inhibitory effects can be further increased to 10-fold by forming a gold nanorod complex (PIH-AuNRs). In addition, PIH-AuNRs display enhanced metabolic stability and biocompatibility in vitro and in vivo and, therefore, effectively prevent MERS-CoV-associated membrane fusion. In summary, PIH-AuNRs represent a novel class of antiviral agents and have a great potential in treating MERS in the clinic.
Cancer cells are susceptible to oxidative stress; therefore, selective elevation of intracellular reactive oxygen species (ROS) is considered as an effective antitumor treatment. Here, a liposomal formulation of dichloroacetic acid (DCA) and metal–organic framework (MOF)‐Fe2+ (MD@Lip) has been developed, which can efficiently stimulate ROS‐mediated cancer cell apoptosis in vitro and in vivo. MD@Lip can not only improve aqueous solubility of octahedral MOF‐Fe2+, but also generate an acidic microenvironment to activate a MOF‐Fe2+‐based Fenton reaction. Importantly, MD@Lip promotes DCA‐mediated mitochondrial aerobic oxidation to increase intracellular hydrogen peroxide (H2O2), which can be consequently converted to highly cytotoxic hydroxyl radicals (•OH) via MOF‐Fe2+, leading to amplification of cancer cell apoptosis. Particularly, MD@Lip can selectively accumulate in tumors, and efficiently inhibit tumor growth with minimal systemic adverse effects. Therefore, liposome‐based combination therapy of DCA and MOF‐Fe2+ provides a promising oxidative stress–associated antitumor strategy for the management of malignant tumors.
Lactic acidosis is one of the key characteristics of the tumor microenvironment (TME), and plays a critical role in therapy resistance, making it an attractive target for enhancing anticancer treatment.
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