Abstract
BackgroundChemotherapy is widely used to treat hepatocellular carcinoma (HCC). Although sorafenib (SO) is the only chemotherapy drug approved by FDA for treatment of HCC, it is associated with several disadvantages including low water solubility, low bioavailability, lack of targeting and easily causes systemic toxicity. In recent years, nanocarriers have shown promise in drug delivery to effectively solve these problems. Herein, we used SO-loaded nanocarriers to overcome the defects of chemotherapy during treatment of HCC. Specifically, we encapsulated pH-sensitive hollow mesoporous Prussian blue nanoparticles (HMPB) with SO (an inhibitor of multi-kinase and accelerant of ferroptosis) to act as carriers and facilitate drug release. We also coated its surface with a layer of pH-responsive chitosan (CS) to block the drug and increase biocompatibility. Finally, we successfully constructed HP/SO/CS nanocomposites for targeted delivery of chemotherapeutic drugs, with the aim of initiating chemotherapy and ferroptosis for dual treatment of tumors. In vitro and in vivo experiments were performed for evaluation of the nanocomposites’ anti-tumor efficacy by using liver cancer cells and mice, respectively.ResultsThe nanocomposites specifically targeted tumor cells through enhancing permeability and retention (EPR) effect. Results from in vitro experiments showed that the nanocarriers not only promoted cell apoptosis and reduced the number of cells for chemotherapy, but also promoted accumulation of reactive oxygen species (ROSs). In vivo experiments showed that mice in the nanocomposite-treated group exhibited the smallest tumor sizes and body weights, with no obvious damage to normal tissues and organs.ConclusionTaken together, these findings indicated that nanocarriers had an effective inhibitory effect on HCC cells. This safe and multifunctional treatment model was a valuable option for the treatment of HCC, as well as other cancers.Graphical
Highlights
Chemotherapy is widely used to treat hepatocellular carcinoma (HCC)
Its surface area and pore size were 288.0571 m2/g and 3.94 nm (Feng et al 2019). These results suggested that the hollow mesoporous structure could be used as ideal carriers for loading of anti-cancer drugs
The surface zeta potential changed from -23.68 to 28.85 mV in Prussian blue (PB) and HP/SO/CS, respectively (Fig. 1C), and this was beneficial for cellular uptake in the tumor microenvironment (TME), because the cell membrane is negatively charged
Summary
Sorafenib (SO) is the only chemotherapy drug approved by FDA for treatment of HCC, it is associated with several disadvantages including low water solubility, low bioavailability, lack of targeting and causes systemic toxicity. We used SO-loaded nanocarriers to overcome the defects of chemotherapy during treatment of HCC. We successfully constructed HP/SO/CS nanocomposites for targeted delivery of chemotherapeutic drugs, with the aim of initiating chemotherapy and ferroptosis for dual treatment of tumors. SO is an oral multi-kinase inhibitor that increases the rate of apoptosis, inhibits proliferation and angiogenesis of tumor cells (Palomba et al 2019). Long-term single drug therapy is detrimental to the outcome of chemotherapy, mainly including high systemic toxicity, low solubility, low oral bioavailability and chemical resistance (Edis et al 2021). Exploring new methods to overcome these shortcomings is imperative to enhance its therapeutic effect
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