Fluorescent Realgar Nanoclusters for Nuclear Targeting-Triggered Tumor Theranostics
ACS APPLIED NANO MATERIALS(2022)
摘要
Realgar as a traditional Chinese medicine for curing cancer has unique advantages, such as great antitumor effect, low genotoxicity, and good organism tolerability. Unfortunately, its poor solubility and body absorptive capacity may cause an extremely low bioavailability. To overcome the therapeutic hurdle, we have successfully synthesized high-performance fluorescent realgar nanoclusters (RNCs), which encapsulate "ethanolamine-modified nano-realgar (NR) assemblies" into functional a poly(ethylene glycol) (PEG)-phospholipid hydrophobic layer, simultaneously coupling with a targeting ligand of hyaluronic acid (HA). As a chemotherapeutic agent, the designed HA-modified RNCs (RNCs@HA) possess excellent water dispersbility, pH-sensitive NR quantum dots (QDs) release capacity, low toxicity, and enhanced anticancer efficacy. As a fluorescent probe, RNCs@HA can be used as an in vivo fluorescence trace system to measure and image biological activity. Herein, we have established a BALB/c mice model bearing a subcutaneous transplanted breast tumor and designed the intravenous RNCs@HA-mediated tumor theranostics in vivo. Under the guidance of targeting HA ligands, RNCs@HA concentrates in the tumor tissue from fenestrated neovascularization, gradually degrades into hydrophobic NR QDs, gathers around nucleopores, and moves into the nucleus regions of cancer cells in an acidic environment, conclusively facilitating nuclear targetingassociated chemotherapy. Our work aims to improve the chemotherapeutic efficacy of realgar and facilitate its more widespread use for clinical application.
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关键词
fluorescent realgar nanoclusters, pH sensibility, nuclear targeting, antitumor activity, tumor theranostics
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