Department of Chemistry, University of Victoria, Victoria, BC V8 W 3 V6, Canada.
Centre for Advanced Materials and Related Technology (CAMTEC), University of Victoria, 3800 Finnerty Rd, Victoria, BC, V8P 5C2, Canada.
Biomater Sci. 2024 Oct 8;12(20):5283-5294. doi: 10.1039/d4bm00480a.
Cancer treatment has transformed in recent years, with the introduction of immunotherapy providing substantial improvements in prognoses for certain cancers. However, traditional small molecule chemotherapeutics remain the major frontline of defence, and improving their delivery to solid tumors is of utmost importance for improving potency and reducing side effects. Here, length-controlled one-dimensional seed nanofibers ( 25 nm, = 1.05) were generated from poly(fluorenetrimethylenecarbonate)--poly(dimethylaminoethylmethacrylate) living crystallization-driven self-assembly. Paclitaxel, with an encapsulation content ranging from 1 to 100 wt%, was loaded onto the preformed nanoparticles by solvent addition and evaporation. Drug loading was quantified by dynamic light scattering and transmission electron microscopy. Drug-loaded vectors were then incubated with U87 MG glioblastoma cells in a 2D cell assay for up to 72 h, and their anticancer properties were determined. It was observed that seed nanofibers loaded with 20 wt% paclitaxel were the most advantageous combination (IC = 0.48 μg mL), while pure seed nanofibers with no loaded drug displayed much lower cytotoxicity (IC = 11.52 μg mL). The IC of the loaded seed nanofibers rivaled that of the commercially approved Abraxane® (IC = 0.46 μg mL). 3D tumor spheroids were then cultured and subjected to the same stresses. Live/dead cell staining revealed that once more, seed nanofibers with 20 wt% paclitaxel, Abraxane®, and paclitaxel all exhibited similar levels of potency (55% viability), whereas control samples exhibited much higher cell viability (70%) after 3 days. These results demonstrate that nanofibers contain great potential as biocompatible drug delivery vehicles for cancer treatment as they exert a similar anticancer effect to the commercially available Abraxane®.
近年来，癌症治疗发生了重大变革，免疫疗法的引入显著改善了某些癌症的预后。然而，传统的小分子化疗药物仍然是主要的一线防御手段，提高它们在实体瘤中的递药效率对于提高疗效和降低副作用至关重要。在这里，我们通过聚（芴基三甲基碳酸酯）-聚（二甲氨基乙基甲基丙烯酸酯）的活的结晶驱动自组装生成了长度可控的一维种子纳米纤维（25nm， = 1.05）。紫杉醇的包封含量范围为 1 至 100wt%，通过溶剂添加和蒸发加载到预形成的纳米颗粒上。通过动态光散射和透射电子显微镜定量测定药物负载。然后将载药载体与 U87 MG 神经胶质瘤细胞在 2D 细胞测定中孵育长达 72 小时，并测定其抗癌特性。结果观察到负载 20wt%紫杉醇的种子纳米纤维是最有利的组合（IC = 0.48 μg mL），而没有负载药物的纯种子纳米纤维显示出较低的细胞毒性（IC = 11.52 μg mL）。负载种子纳米纤维的 IC 与市售的 Abraxane®（IC = 0.46 μg mL）相当。然后培养 3D 肿瘤球体并施加相同的压力。活/死细胞染色显示，负载 20wt%紫杉醇的种子纳米纤维、Abraxane®和紫杉醇再次表现出相似的效力（55%的存活率），而对照样品在 3 天后显示出更高的细胞存活率（70%）。这些结果表明，纳米纤维作为癌症治疗的生物相容药物载体具有很大的潜力，因为它们与市售的 Abraxane®具有相似的抗癌效果。
