Biomimetic Red Blood Cell Membrane-Mediated Nanodrugs Loading Ursolic Acid for Targeting NSCLC Therapy

SIMPLE SUMMARY: Lung cancer is the second most common cancer after breast cancer. Non-small-cell lung cancer, which represents more than 85% of all lung cancer subtypes, is known for its tumor progression and metastasis, resulting in poor clinical outcomes. Conventional therapies for NSCLC, such as surgery, chemotherapy, and radiotherapy, always fail due to therapeutic resistance. In recent years, ursolic acid (UA), a natural pentacyclic triterpenoid compound, has been shown to be a promising antitumor drug by regulating multiple signaling pathways in cancers. Unfortunately, the poor water solubility, low bioavailability, and systemic toxicity of UA limit its clinical application. In this study, a biomimetic red blood cell membrane nanocarrier was developed to deliver UA to targeted tumor sites efficiently, and it inhibited tumor growth by inducing the apoptosis and autophagy of cancer cells both in vitro and in vivo. ABSTRACT: As one of the most common cancers worldwide, non-small-cell lung cancer (NSCLC) treatment always fails owing to the tumor microenvironment and resistance. UA, a traditional Chinese medicine, was reported to have antitumor potential in tumor models in vitro and in vivo, but showed impressive results in its potential application for poor water solubility. In this study, a novel biomimetic drug-delivery system based on UA-loaded nanoparticles (UaNPs) with a red blood cell membrane (RBCM) coating was developed. The RBCM-coated UANPs (UMNPs) exhibited improved water solubility, high stability, good biosafety, and efficient tumor accumulation. Importantly, the excellent antitumor efficiency of the UMNPs was confirmed both in vitro and in vivo in cancer models. In addition, we further investigated the antitumor mechanism of UMNPs. The results of Western blotting showed that UMNPs exerted an anticancer effect by inducing the apoptosis and autophagy of NSCLC cells, which makes it superior to free UA. In addition, body weight monitoring, hematoxylin and eosin (HE) analysis, and immunohistochemical (IHC) analysis showed no significant difference between UMNPs and the control group, indicating the safety of UMNPs. Altogether, the preparation of biomimetic UMNPs provides a promising strategy to improve outcomes in NSCLC.