School of Chemical Engineering, University of New South Wales, Sydney, NSW, 2052, Australia.
Chongqing Key Laboratory of Ultrasound Molecular Imaging, Institute of Ultrasound Imaging, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, P. R. China.
Small. 2022 Jun;18(22):e2200299. doi: 10.1002/smll.202200299. Epub 2022 May 6.
Nanoparticle drug delivery is largely restricted by the low drug loading capacity of nanoparticle carriers. To address this critical challenge and maximize the potential of nanoparticle drug delivery, a 2D ultra-thin layered double hydroxide (LDH) nanosheet with exceptionally high drug loading, excellent colloidal stability, and prolonged blood circulation for cancer treatment is constructed. The nanosheet is synthesized via a biocompatible polymer-assisted bottom-up method and exhibits an ultra-thin 2D sheet-like structure that enables a considerable amount of cargo anchoring sites available for drug loading, leading to an extraordinary 734% (doxorubicin/nanoparticle mass ratio) drug loading capacity. Doxorubicin delivered by the nanosheet remains stable on the nanosheet carrier under the physiological pH condition, while showing sustained release in the tumor microenvironment and the intracellular environment, thus demonstrating on-demand drug release as a result of pH-responsive biodegradation of nanosheets. Using in vitro and in vivo 4T1 breast cancer models, the nanosheet-based ultra-high drug-loading system demonstrates even enhanced therapeutic performance compared to the multilayered LDH-based high drug-loading system, in terms of increased cellular uptake efficiency, prolonged blood circulation, superior therapeutic effect, and reduced systemic toxicity.
纳米颗粒药物递送在很大程度上受到纳米颗粒载体低载药能力的限制。为了解决这一关键挑战，最大限度地发挥纳米颗粒药物递送的潜力，构建了一种具有超高载药能力、出色胶体稳定性和延长血液循环时间的二维超薄层状双氢氧化物（LDH）纳米片用于癌症治疗。该纳米片通过生物相容性聚合物辅助的自下而上的方法合成，具有超薄片层状的 2D 结构，可提供大量的货物锚定位点用于药物负载，从而实现了非凡的 734%（阿霉素/纳米颗粒质量比）的载药能力。在生理 pH 条件下，纳米片中的阿霉素在纳米片载体上保持稳定，而在肿瘤微环境和细胞内环境中则表现出持续释放，从而表现出按需药物释放，这是由于纳米片的 pH 响应性生物降解。使用体外和体内 4T1 乳腺癌模型，基于纳米片的超高载药系统在细胞摄取效率提高、血液循环延长、治疗效果更好和全身毒性降低等方面，与基于多层 LDH 的高载药系统相比，甚至表现出增强的治疗性能。
