Wong Erica, Staskiewicz Anna, Pruner Joshua, Lee Jean, Tucker Michael, Smith Barkley, Rogers Lanerica, Asuni Ganiat, Wang Xinyu
Department of Inpatient Pharmacy, Lucile Packard Children's Hospital Stanford, Palo Alto, CA, United States.
Graduate Division of Biological and Biomedical Sciences, Biochemistry, Cell and Developmental Biology Graduate Program, Emory University, Atlanta, GA, United States.
Front Pharmacol. 2025 Jun 17;16:1589090. doi: 10.3389/fphar.2025.1589090. eCollection 2025.
Natural compounds have emerged as promising therapeutic agents for treating cancers such as multiple myeloma (MM). However, poor bioavailability, low stability, and suboptimal targeting often limit their clinical efficacy. Recent advances in nanotechnology have addressed these limitations by utilizing nanoparticle (NP) carriers to enhance the therapeutic potential of natural compounds through improved solubility, stability, and selective delivery to cancer cells. This review explores the inhibitory effects of key natural compounds on MM cells, including 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) and its derivatives, caffeic acid phenethyl ester (CAPE) and its derivatives, xanthohumol (XN) and its derivatives, resveratrol (RSV) and its derivatives, curcumin (CUR), 3,4,5-trihydroxybenzoic acid (gallic acid; GA), and evodiamine (EVO). These compounds exhibit potent anti-proliferative, pro-apoptotic, and anti-inflammatory properties through the modulation of signaling pathways such as NF-κB, STAT3, and PI3K/Akt, which are critical in MM pathogenesis. Despite their therapeutic promise, the clinical application of these natural agents has been hampered by pharmacokinetic challenges. NP carriers, including liposomes, polymeric NPs, and lipid-based nanocarriers, have been engineered to improve these compounds' bioavailability and targeted delivery, enhancing their cytotoxicity against MM cells. For instance, CDDO and its derivatives encapsulated in NPs have demonstrated increased intracellular accumulation and improved inhibition of NF-κB activity. Similarly, NP formulations of CAPE, XN, and RSV have enhanced anti-MM effects through improved stability and sustained drug release. CUR, known for its poor water solubility, has seen its therapeutic potential augmented through NP delivery systems, enabling higher drug concentrations at tumor sites. Though structurally distinct, GA and EVO have benefited from NP-based enhancement, exhibiting improved bioavailability and selective targeting of MM cells. This review highlights the promising role of NP carriers in overcoming the pharmacokinetic limitations of natural compounds, offering new avenues for more effective MM therapies.
天然化合物已成为治疗多发性骨髓瘤（MM）等癌症的有前景的治疗剂。然而，生物利用度差、稳定性低和靶向性欠佳常常限制了它们的临床疗效。纳米技术的最新进展通过利用纳米颗粒（NP）载体来解决这些局限性，通过改善溶解性、稳定性以及对癌细胞的选择性递送，增强天然化合物的治疗潜力。本综述探讨了关键天然化合物对MM细胞的抑制作用，包括2-氰基-3,12-二氧代齐墩果-1,9-二烯-28-酸（CDDO）及其衍生物、咖啡酸苯乙酯（CAPE）及其衍生物、黄腐酚（XN）及其衍生物、白藜芦醇（RSV）及其衍生物、姜黄素（CUR）、3,4,5-三羟基苯甲酸（没食子酸；GA）和吴茱萸碱（EVO）。这些化合物通过调节诸如NF-κB、STAT3和PI3K/Akt等信号通路，展现出强大的抗增殖、促凋亡和抗炎特性，而这些信号通路在MM发病机制中至关重要。尽管它们具有治疗前景，但这些天然药物的临床应用受到药代动力学挑战的阻碍。NP载体，包括脂质体、聚合物NP和基于脂质的纳米载体，已被设计用于改善这些化合物的生物利用度和靶向递送，增强它们对MM细胞的细胞毒性。例如，封装在NP中的CDDO及其衍生物已显示出细胞内积累增加以及对NF-κB活性的抑制作用增强。同样，CAPE、XN和RSV的NP制剂通过提高稳定性和持续药物释放增强了抗MM作用。CUR以其水溶性差而闻名，通过NP递送系统其治疗潜力得到增强，能够在肿瘤部位实现更高的药物浓度。尽管GA和EVO在结构上不同，但它们受益于基于NP的增强作用，表现出改善的生物利用度和对MM细胞的选择性靶向。本综述强调了NP载体在克服天然化合物药代动力学局限性方面的有前景的作用，为更有效的MM治疗提供了新途径。
