**Xinyue Dong, Jin Gao, Yujie Su and Zhenjia Wang \***

Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, WA 99202, USA; xinyue.dong@wsu.edu (X.D.); jin.gao3@wsu.edu (J.G.); yujie.su@wsu.edu (Y.S.) **\*** Correspondence: zhenjia.wang@wsu.edu

Received: 29 September 2020; Accepted: 12 October 2020; Published: 14 October 2020

**Abstract:** Stroke is a severe brain disease leading to disability and death. Ischemic stroke dominates in stroke cases, and there are no effective therapies in clinic, partly due to the challenges in delivering therapeutics to ischemic sites in the brain. This review is focused on the current knowledge of pathogenesis in ischemic stroke, and its potential therapies and diagnosis. Furthermore, we present recent advances in developments of nanoparticle-based therapeutics for improved treatment of ischemic stroke using polymeric NPs, liposomes and cell-derived nanovesicles. We also address several critical questions in ischemic stroke, such as understanding how nanoparticles cross the blood brain barrier and developing in vivo imaging technologies to address this critical question. Finally, we discuss new opportunities in developing novel therapeutics by targeting activated brain endothelium and inflammatory neutrophils to improve the current therapies for ischemic stroke.

**Keywords:** ischemic stroke; blood brain barrier; nanoparticle-based drug delivery; brain targeting
