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CD-PEI-mediated doxorubicin specifically targets HCC tumors, enabling real-time monitoring and therapeutic efficacy through growth inhibition and apoptosis induction.

Rationale : Current therapies for hepatocellular carcinoma (HCC) are hampered by treatment failure and recurrence due to the remaining treatment-resistant liver cancer stem cells (CSCs). Stemness and epithelial-mesenchymal transition (EMT) are regarded as two fundamental characteristics of liver CSCs necessary for cancer progression; thus, drugs that simultaneously target both characteristics should prove effective in eliminating HCC and impeding recurrence. In this study, we developed new arsenic trioxide (ATO)-based nanoparticles (NPs), which are expected to be more effective than the current HCC therapy, and explored their potential mechanism. Methods : A “one-pot” reverse emulsification approach was employed to prepare the ZnAs@SiO 2 NPs. HCC cell lines, MHCC97L and Hep3b, were used to analyze the antitumor activity of ZnAs@SiO 2 NPs in vitro and in vivo by quantifying cell growth and metastasis as well as to study the effect on stemness and EMT. SHP-1 siRNA was used to validate the role of the SHP-1/JAK2/STAT3 signaling pathway in mediating inhibition of stemness and EMT by ZnAs@SiO 2 . Results : Compared with the current ATO treatment, ZnAs@SiO 2 NPs promoted apoptosis and significantly inhibited proliferation, migration, and invasion of both MHCC97L and Hep3b cells. In the in vivo assay, ZnAs@SiO 2 NPs inhibited tumor growth by 2.2-fold and metastasis by 3.5-fold as compared to ATO. The ZnAs@SiO 2 NPs also inhibited tumor spheroid formation in vitro and tumor initiation in vivo and induced significant changes in the expression of stemness markers (CD133, Sox-2, and Oct-4) and EMT markers (E-cadherin, Vimentin, and Slug) both in vitro and in vivo. These effects of ZnAs@SiO 2 that correlated with prognosis of HCC were mediated by the SHP-1/JAK2/STAT3 signaling. Conclusions : ZnAs@SiO 2 NPs can effectively suppress tumor initiation, growth, metastasis, and inhibit stemness and EMT through regulation of SHP-1/JAK2/STAT3 signaling pathway in liver cancer cells in vitro and in vivo . Thus, ZnAs@SiO 2 NPs have immense potential for HCC treatment in the future.

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Currently, treatment of intracranial diseases still remains a great challenge because the blood–brain barrier (BBB) blocks access of most drugs to the central nervous system. Herein, a theranostic small molecular probe, iRGD‐ICG‐Lys‐DTPA@Gd (iRGD‐ILD), capable of crossing BBB is developed. Owing to the small molecular size and αvβ3 integrin receptor–mediated transcytosis, this tailor‐made molecular probe integrating the fluorescence and magnetic resonance imaging functions effectively passes through BBB to target tumor cells even in the early stage of glioblastoma multiforme (GBM), thereby allowing a bimodal imaging–guided therapy of GBM. The reactive oxygen species and heat generated by the ICG moiety under the 808 nm laser irradiation exert photodynamic/photothermal therapeutic effects, which results in significantly inhibited tumor growth and prolonged median survival of C6‐Luc glioma‐bearing mice. Notably, the integration of FDA‐approved clinically available agents, e.g., ICG, DTPA and Gd, into a molecular probe may ensure desirable biocompatibility and biosafety for in vivo applications. Overall, the results highlight the potential of a water‐soluble small molecule as a novel theranostic probe for highly effective GBM treatment.

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