Cancer Research Center, Medical College, Xiamen University, Xiamen 361005, China; Department of Biomaterials and Research Center of Biochemical Engineering, College of Materials, Xiamen University, Xiamen 361005, China; Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.
Department of Biomaterials and Research Center of Biochemical Engineering, College of Materials, Xiamen University, Xiamen 361005, China.
Mater Sci Eng C Mater Biol Appl. 2019 Dec;105:110107. doi: 10.1016/j.msec.2019.110107. Epub 2019 Aug 21.
Recently, chemotherapy is still widely exploited to treat the residual, infiltrative tumor cells after surgical resection. However, many anticancer drugs are limited in clinical application due to their poor water-solubility (hydrophibic) and stability, low bioavailability, and unfavorable pharmacokinetics. Herein, an amphiphilic stearic acid-O-carboxymethyl chitosan (SA-CMC) conjugate was synthesized by amide linkage of SA to the backbone of CMC polymer and then self-assembled into nanoparticles (SA-CMC NPs) with the hydrodynamic particle size of ~100 nm. Subsequently, Paclitaxel (PTX) as a potent and broad-spectrum anticancer drug was loaded into SA-CMC NPs by a probe sonication combined with dialysis method. Owing to the multi-hydrophobic inner cores, the prepared PTX-SA-CMC NPs showed a considerable drug-loading capacity of ~19 wt% and a biphasic release behavior with an accumulative release amount in the range of 70-90% within 72 h. PTX-SA-CMC NPs remarkably enhanced the accumulation at the tumor sites by passive targeting followed by cellular endocytosis. Upon the stimuli of acid, PTX-SA-CMC NPs showed exceptional instability by pH change, thereby triggering the rapid disassembly and accelerated drug release. Consequently, compared with Cremophor EL-based free PTX treatment, PTX-SA-CMC NPs under pH-stimuli accomplished highly efficient apoptosis in cancer cells and effectively suppression of tumors by chemotherapy. Overall, PTX-SA-CMC NPs integrating imaging capacity might be a simple yet feasible PTX nanosystem for tumor-targeted delivery and cancer therapy.
最近，化疗仍然被广泛用于治疗手术切除后残留的浸润性肿瘤细胞。然而，许多抗癌药物由于其较差的水溶性（疏水性）和稳定性、低生物利用度以及不利的药代动力学而在临床应用中受到限制。在此，通过酰胺键将硬脂酸（SA）连接到 CMC 聚合物的主链上，合成了一种两亲性的硬脂酸-O-羧甲基壳聚糖（SA-CMC）偶联物，然后自组装成水动力粒径约为 100nm 的纳米颗粒（SA-CMC NPs）。随后，通过探针超声结合透析法将作为一种强效且广谱抗癌药物的紫杉醇（PTX）负载到 SA-CMC NPs 中。由于具有多个疏水性内核，所制备的 PTX-SA-CMC NPs 表现出相当高的载药能力（约 19wt%）和两相释放行为，在 72h 内累计释放量在 70-90%范围内。PTX-SA-CMC NPs 通过被动靶向和随后的细胞内吞作用显著增强了在肿瘤部位的积累。在酸的刺激下，PTX-SA-CMC NPs 由于 pH 值的变化而表现出异常的不稳定性，从而触发快速解组装和加速药物释放。因此，与基于 Cremophor EL 的游离 PTX 治疗相比，在 pH 刺激下的 PTX-SA-CMC NPs 在癌细胞中实现了高效的细胞凋亡，并通过化学疗法有效抑制了肿瘤。总的来说，具有成像能力的 PTX-SA-CMC NPs 可能是一种简单而可行的用于肿瘤靶向递药和癌症治疗的 PTX 纳米系统。
