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，化学疗法仍被广泛用于治疗手术切除后残留的浸润性肿瘤细胞。但是，许多抗癌药物由于其水溶性差（疏水性）和稳定性差，生物利用度低以及药代动力学不良而在临床上受到限制。这里，两亲硬脂酸-O通过SA与CMC聚合物主链的酰胺键合成α-羧甲基壳聚糖（SA-CMC）共轭物，然后自组装成流体动力学粒径约为100 nm的纳米颗粒（SA-CMC NPs）。随后，通过探针超声结合透析方法，将紫杉醇（PTX）作为有效的广谱抗癌药物装载到SA-CMC NP中。由于具有多疏水性的内核，因此制备的PTX-SA-CMC NP表现出相当大的载药量，约为19 wt％，并且在72 h内具有双相释放行为，累积释放量在70-90％的范围内。PTX-SA-CMC NPs通过被动靶向和随后的细胞内吞作用显着增强了肿瘤部位的蓄积。受到酸刺激后，PTX-SA-CMC NPs会因pH变化而表现出异常的不稳定性，从而触发快速拆卸和加速药物释放。因此，与基于Cremophor EL的免费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地抑制了肿瘤。总体而言，整合了成像能力的PTX-SA-CMC NPs可能是一个简单而可行的PTX纳米系统，用于肿瘤靶向递送和癌症治疗。