Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing 210009, China.
Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.
Mol Pharm. 2023 Nov 6;20(11):5463-5475. doi: 10.1021/acs.molpharmaceut.3c00310. Epub 2023 Oct 12.
Nonsmall cell lung cancer (NSCLC) remains one of the leading causes of cancer-related death worldwide, posing a serious threat to global health. Tetrandrine (Tet) is a small molecule in traditional Chinese medicine with proven primary efficacy against multiple cancers. Although previous studies have demonstrated the potential anticancer effects of Tet on NSCLC, its poor water solubility has limited its further clinical application. Herein, a novel nanoparticle-based drug delivery system, platelet membrane (PLTM)-coated Tet-loaded polycaprolactone--poly(ethylene glycol)--polycaprolactone nanoparticles (PTeNPs), is proposed to increase the potency of Tet against NSCLC. First, tetrandrine nanoparticles (TeNPs) are created using an emulsion solvent evaporation method, and biomimetic nanoparticles (PTeNPs) are prepared by coating the nanoparticles with PLTMs. When coated with PLTMs, PTeNPs are considerably less phagocytized by macrophages than Tet and TeNPs. In addition, compared with Tet and TeNPs, PTeNPs can significantly inhibit the growth and invasion of NSCLC both in vitro and in vivo. With reliable biosafety, this drug delivery system provides a new method of sustained release and efficient anticancer effects against NSCLC, facilitating the incorporation of Tet in modern nanotechnology.
非小细胞肺癌(NSCLC)仍然是全球癌症相关死亡的主要原因之一,对全球健康构成严重威胁。汉防己甲素(Tet)是一种中药中的小分子,已被证明对多种癌症具有主要疗效。尽管先前的研究已经证明 Tet 对 NSCLC 具有潜在的抗癌作用,但它的水溶性差限制了其进一步的临床应用。在此,提出了一种基于纳米颗粒的新型药物递送系统,血小板膜(PLTM)包裹的载汉防己甲素的聚己内酯-聚(乙二醇)-聚己内酯纳米粒(PTeNPs),以提高 Tet 对 NSCLC 的效力。首先,使用乳化溶剂蒸发法制备汉防己甲素纳米粒(TeNPs),然后通过用 PLTM 涂覆纳米粒来制备仿生纳米粒(PTeNPs)。当用 PLTM 包裹时,PTeNPs 被巨噬细胞吞噬的程度明显低于 Tet 和 TeNPs。此外,与 Tet 和 TeNPs 相比,PTeNPs 无论是在体外还是体内都能显著抑制 NSCLC 的生长和侵袭。该药物递送系统具有可靠的生物安全性,为 NSCLC 的持续释放和高效抗癌作用提供了一种新方法,促进了 Tet 在现代纳米技术中的应用。