**5. Nanomedicine in Liver Fibrosis Theranostics**

"Theranostics", a portmanteau word of "therapeutics" and "diagnostics", is achieved by incorporating diagnostic and therapeutic functions into a single nanoplatform. Theranostics has been proposed as a new and revolutionary therapeutic concept in several types of disease therapy, including that for liver fibrosis [107]. This strategy allows simultaneous diagnosis and treatment response by using personalized medicine with high accuracy and specificity. In one study, Hepatitis B core protein nanocages coated with RGD-targeting ligands (RGD–HBc/QR) exhibited selectivity to activated HSCs by targeting integrin αvβ<sup>3</sup> and efficiently inhibited the proliferation and activation of HSCs both in vitro and in vivo [108]. By encapsulating a quercetin–gadolinium complex and/or labeling it with NIR fluorescent probes (Cy5.5), the resulted nanoformulations (RGD–HBc/QGd) showed great potential as MRI contrast agents and NIR fluorescent agents for liver fibrosis diagnosis in vivo. Another study reported that relaxin-conjugated PEGylated superparamagnetic iron oxide NPs (RLX-SPIONs) showed specific binding and uptake in TGFβ-activated HSCs, as well as strongly attenuated cirrhosis and showed enhanced contrast in MRI [20]. Micelles coupled with inorganic materials were also developed for theranostics to treat liver fibrosis. A pH-sensitive and VA-conjugated copolymer cationic micelle that was coupled with a superparamagnetic iron oxide nanoparticle could transport miRNA-29b and miRNA-112 to HSCs in an MRI-visible manner. Synergistic antifibrotic therapeutic efficacy was achieved by downregulating the expression of fibrosis-related genes, including collagen Iα1, α-SMA, and a tissue inhibitor of MMP1 (Figure 5) [109].

**Figure 5.** Vitamin A–decorated pH-sensitive and SPIO-loaded nanocomplex T-PBP@miRNA/SPIO (T-miRNA/S) for miRNA targeting delivery in the therapy of liver fibrosis. Expression of liver fibrosis-related genes for alleviating liver fibrosis were synergistically downregulated. The red arrows indicate the reduction of COL1A1, TIMP1, and collagen fiber. Abbreviations: COL1A1, collagen type I alpha 1 protein; TIMP1, tissue inhibitor of metalloproteinase 1; SPIO, superparamagnetic iron oxide. Reproduced with permission from [109]. Copyright John Wiley and Sons, 2019.
