Layer-by-layer approach based on the electrostatic interactions has been introduced to make multi-layered targeting ligand-chemotherapeutics-cellulose nanocrystal (CNC) structure for tumor-targeted drug delivery. Negatively charged CNC was covered with cationic doxorubicin (DOX) molecule (as a chemotherapeutic agent) to fabricate DOX@CNC and sequentially wrapped with anionic hyaluronic acid (HA) polymer (as a CD44 receptor targeting ligand). Rod-shaped HA-coated DOX@CNC (HA@DOX@CNC) has been successfully fabricated and it exhibited 327 nm length, 12 nm width, −38 mV zeta potential, and 3% DOX content. HA@DOX@CNC displayed higher cellular accumulation efficiency and antiproliferation potentials in CD44 receptor-positive lung adenocarcinoma (A549) cells compared to DOX and DOX-wrapped CNC (DOX@CNC). In A549 spheroid model, HA@DOX@CNC group exhibited superior tumor penetration capability, reactive oxygen species (ROS) production level, and cancer cell killing capacity rather than DOX and DOX@CNC group. In A549 tumor implanted mouse model, Cy5.5-labeled HA@DOX@CNC group exhibited higher tumor accumulation efficiency rather than free Cy5.5 after intravenous injection. All these findings suggest that designed HA@DOX@CNC can be one of promising biocompatible tumor-targeted nano-size drug delivery systems.

已经引入了基于静电相互作用的逐层方法，以制造用于肿瘤靶向药物递送的多层靶向配体-化学疗法-纤维素纳米晶体（CNC）结构。带有负电荷的CNC用阳离子阿霉素（DOX）分子（作为化学治疗剂）覆盖，以制造DOX @ CNC，然后依次用阴离子透明质酸（HA）聚合物（作为CD44受体靶向配体）包裹。棒状HA涂层DOX @ CNC（HA @ DOX @ CNC）已成功制造，其长度为327 nm，宽度为12 nm，-38 mVζ电位和3％DOX含量。与DOX和DOX包裹的CNC（DOX @ CNC）相比，HA @ DOX @ CNC在CD44受体阳性的肺腺癌（A549）细胞中显示出更高的细胞蓄积效率和抗增殖潜力。在A549球体模型中，HA @ DOX @ CNC组比DOX和DOX @ CNC组具有更好的肿瘤渗透能力，活性氧（ROS）产生水平和癌细胞杀伤能力。在A549肿瘤移植小鼠模型中，Cy5.5标记的HA @ DOX @ CNC组在静脉注射后显示出更高的肿瘤蓄积效率，而不是游离的Cy5.5。所有这些发现表明，设计的HA @ DOX @ CNC可以成为有前途的生物相容性肿瘤靶向纳米级药物递送系统之一。