Hunan Provincial Key Laboratory of Micro & Nano Materials Interface Science, College of Chemistry and Chemical Engineering, Central South University, Changsha, 410083, PR China.
Key Laboratory of Molecular Medicine and Biotherapy, School of Life Sciences, Beijing Institute of Technology, Beijing, 100081, PR China.
Biomaterials. 2021 Jan;268:120557. doi: 10.1016/j.biomaterials.2020.120557. Epub 2020 Nov 23.
Nanocarrier-based drug delivery systems hold impressive promise for biomedical application because of their excellent water dispersibility, prolonged blood circulation time, increased drug accumulation in tumors, and potential in combination therapeutics. However, most nanocarriers suffer from low drug-loading efficiency, poor therapeutic effectiveness, potential systematic toxicity, and unstable metabolism. As an alternative, carrier-free nanodrugs, completely formulated with one or more drugs, have attracted increasing attention in cancer therapy due to their advantage of improved pharmacodynamics/pharmacokinetics, reduced toxicity, and high drug-loading. In recent years, carrier-free nanodrugs have contributed to progress in a variety of therapeutic modalities. In this review, different common strategies for carrier-free nanodrugs preparation are first summarized, mainly including nanoprecipitation, template-assisted nanoprecipitation, thin-film hydration, spray-drying technique, supercritical fluid (SCF) technique, and wet media milling. Then we describe the recently reported carrier-free nanodrugs for cancer chemo-monotherapy or combination therapy. The advantages of anti-cancer drugs combined with other chemotherapeutic, photosensitizers, photothermal, immunotherapeutic or gene drugs have been demonstrated. Finally, a future perspective is introduced to highlight the existing challenges and possible solutions toward clinical application of currently developed carrier-free nanodrugs, which may be instructive to the design of effective carrier-free regimens in the future.
基于纳米载体的药物传递系统因其出色的水分散性、延长的血液循环时间、增加肿瘤内药物积累以及在联合治疗中的潜力，在生物医学应用中具有令人印象深刻的前景。然而，大多数纳米载体存在载药效率低、治疗效果差、潜在的系统毒性和不稳定的代谢等问题。作为替代方案，完全由一种或多种药物组成的无载体纳米药物在癌症治疗中引起了越来越多的关注，因为它们具有改善的药效学/药代动力学、降低的毒性和高载药效率的优势。近年来，无载体纳米药物在多种治疗模式中取得了进展。在这篇综述中，首先总结了无载体纳米药物制备的几种常见策略，主要包括纳米沉淀法、模板辅助纳米沉淀法、薄膜水化法、喷雾干燥技术、超临界流体（SCF）技术和湿介质研磨法。然后我们描述了最近报道的用于癌症化疗或联合治疗的无载体纳米药物。已经证明了抗癌药物与其他化疗药物、光敏剂、光热剂、免疫治疗或基因药物联合使用的优势。最后，引入了未来展望，以突出目前开发的无载体纳米药物向临床应用所面临的挑战和可能的解决方案，这可能对未来有效的无载体方案的设计具有指导意义。
