Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal solid cancers globally. To improve diagnosis sensitivities and treatment efficacies, the development of new theranostic nanoplatforms for efficient HCC management is urgently needed. In the past decade, mesoporous silica nanoparticles (MSNs) with tailored structure, large surface area, high agents loading volume, abundant chemistry functionality, acceptable biocompatibility have received more and more attention in HCC theranostic. This review outlines the recent advances in MSNs-based systems for HCC therapy and diagnosis. The multifunctional hybrid nanostructures that have both of therapy and diagnosis abilities are highlighted. And the precision delivery strategies of MSNs in HCC are also discussed. Final, we conclude with our personal perspectives on the future development and challenges of MSNs.
Background
There is currently no effective treatment for advanced hepatocellular carcinoma (HCC), and chemotherapy has little effect on long-term survival of HCC patients, largely due to the cancer stem cell (CSC) chemoresistance of HCC.
Methods
We constructed a small-molecule nanometer-sized prodrug (nanoprodrug) loaded with salinomycin (SAL) for the treatment of HCC. SAL was encapsulated by the prodrug LA-SN38 (linoleic acid modified 7-ethyl-10-hydroxycamptothecin) to construct a self-assembled nanoprodrug further PEGylated with DSPE-PEG
2000
. We characterized this codelivered nanoprodrug and its antitumor activity both in vitro in human HCC cell lines and in vivo in mice.
Results
Delivery of the SAL- and LA-SN38-based nanoprodrugs effectively promoted apoptosis of HCC cells, exerted inhibition of HCC tumor-sphere formation as well as HCC cell motility and invasion, and reduced the proportion of CD133+ HCC-CSC cells. In nude mice, the nanoprodrug suppressed growth of tumor xenografts derived from human cell lines and patient.
Conclusion
Our results show that SAL-based nanoprodrugs are a promising platform for treating patients with HCC and a novel strategy for combination therapy of cancers.
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