Contents lists available at ScienceDirect International Journal of Pharmaceutics journal homepage: www.elsevier.com/locate/ijpharm Review Copper sulfide: An emerging adaptable nanoplatform in cancer theranostics Kishwor Poudel a , Milan Gautam a , Sung Giu Jin b , Han-Gon Choi c , Chul Soon Yong a, ⁎ , Jong Oh Kim a, ⁎ a College of Pharmacy, Yeungnam University, 280 Daehak-Ro, Gyeongsan 712-749, Republic of Korea b Department of Pharmaceutical Engineering, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan 31116, Republic of Korea c College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan 15588, Republic of Korea ARTICLE INFO Keywords: Copper sulfide Nanoplatforms Therapeutics Theranostics ABSTRACT Copper sulfide nanoparticles (CuS NPs), emerging nanoplatforms with dual diagnostic and therapeutic appli- cations, are being actively investigated in this era of “war on cancer” owing to their versatility and adaptability. This article discusses the pros and cons of using CuS NPs in diagnostics, therapeutics, and theranostics. The first section introduces CuS NPs and discusses the features that render them more advantageous than other estab- lished nanoplatforms in cancer management. Subsequent sections include specific in vitro and in vivo results of different studies showing the potential of CuS NPs as nanoplatforms. Methods used for visualization (photo- acoustic imaging and magnetic resonance imaging) of CuS NPs and treatment (phototherapy and combinatorial therapy) have also been discussed. Furthermore, the challenges and opportunities associated with using CuS NPs have been elucidated. Further investigations on CuS NPs are required to translate it for clinical applications. 1. Introduction Nanotechnology, a promising technology with remarkable out- comes, has been used to develop numerous therapeutic nanoplatforms for treating cancer. Nanotools of various shapes have been synthesized, such as nanospheres, nanocubes, nanowires, nanorods, and nanoshells with hollow core as well as mesoporous surfaces (Banstola et al., 2018; Gautam et al., 2018; ho Hong and Choi, 2018; Hoang et al., 2017; Singh et al., 2015; Tan et al., 2016). Some of these nanotools have been ap- proved by the Food and Drug Administration (FDA), whereas others are in clinical trials (Shi et al., 2017). Indeed, nanomedicine has been successfully used to develop theranostic platforms for cancer therapy (Dai et al., 2017; Shi et al., 2017; Thakor and Gambhir, 2013). Versatile nanoplatforms with higher scope of diagnostics and therapeutics have attracted attention in precision medicine (Bardhan et al., 2011; Kim et al., 2009; Lee et al., 2012). Compared to other organic nanoparticles, inorganic nanoparticles such as silica, iron oxide, and gold are in the limelight for theranostic purposes (Anselmo and Mitragotri, 2015; Anselmo and Mitragotri, 2016). In addition, inorganic nanoparticles are attracting more attention because of their remarkable outcomes in the pre-clinical and clinical stages of drug design and development. The adaptability of inorganic nanotools to diagnostic and therapeutic design has made them viable candidates for future applications. Iron oxide nanoparticles are established nanotheranostic platforms in clinical trials against several types of cancer (Shi et al., 2017; Thakor and Gambhir, 2013). Silica nanoparticles and gold nanoparticles (GNPs) are also being used in clinical trials for cancer imaging and thermal abla- tion of tumors, respectively. Similarly, copper sulfide nanoparticles (CuS NPs) are potent theranostic nanotools with promising outcomes (Goel et al., 2014; Li et al., 2017a; Xu et al., 2012). This review dis- cusses various CuS NPs as emerging adaptable nanoplatforms in cancer theranostics. 2. CuS NPs CuS NPs semi-conductors have been extensively studied for their multifunctional properties (Goel et al., 2014). They have also emerged as promising and adaptable agents for cancer theranostics because of their diverse diagnostic and therapeutic potential (Feng et al., 2016; Guo et al., 2014; Zhou et al., 2015c). Among various inorganic mate- rials, this nanoparticle is attracting maximum attention because of biocompatibility, low toxicity, and low cost (Feng et al., 2016; Wang, 2016; Wang et al., 2016b). The near-infrared (NIR) absorption of CuS NPs is acquired from the d–d transition of Cu 2+ ions, which show NIR absorption at 700–1100 nm. The absorption does not depend on the dielectric constant of the surrounding medium and changes negligibly with morphology (Wang, 2016; Zha et al., 2013b; Zhang et al., 2013). In contrast, the absorbance of GNPs, which depends upon surface https://doi.org/10.1016/j.ijpharm.2019.03.043 Received 11 January 2019; Received in revised form 18 March 2019; Accepted 19 March 2019 ⁎ Corresponding authors. E-mail addresses: csyong@ynu.ac.kr (C.S. Yong), jongohkim@yu.ac.kr (J.O. Kim). International Journal of Pharmaceutics 562 (2019) 135–150 Available online 20 March 2019 0378-5173/ © 2019 Elsevier B.V. All rights reserved. T