School of Biomedical Sciences, The University of Queensland, Brisbane, Queensland 4072, Australia.
Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
J Control Release. 2020 Nov 10;327:512-532. doi: 10.1016/j.jconrel.2020.08.016. Epub 2020 Aug 13.
Nanoparticles (NPs) that permit active targeting promise to play a key role in cancer therapy moving forward. However, in order to successfully advance into clinic, these delivery platforms not only must target individual tumoural cellular components but also require safe, efficient and scalable production. Herein, we review recent and innovative targeted nanoparticle delivery strategies to individual TME components, including cancer-associated blood and lymphatic vessels, pericytes, cancer associated fibroblasts, and cancer stem cells. In contrast to traditional therapies that promote widespread ablation, emerging nano-strategies that specifically modulate different cell populations of the TME, such as targeting pericytes and endothelial cells for vascular normalization, are proving to effectively deliver therapeutics to tumours. Additionally, new smart targeted NPs with transformable characteristics responsive to specific tumour microenvironmental cues demonstrate enhanced spatiotemporal control over cell targeting and therapeutic release. However, translating these therapies to the clinic requires overcoming several significant barriers such as failure to recapitulate the human TME in animal models and issues with NP targeting efficacy, safety and scalable production. We discuss recent efforts to overcome these challenges and innovative means to reduce off-target toxicities. We also highlight important deficiencies in current NP development and offer new perspectives on the design of pre-clinical and clinical trials to accelerate clinical translation of targeted NP platforms.
纳米颗粒 (NPs) 能够实现主动靶向，有望在癌症治疗中发挥关键作用。然而，为了成功推向临床，这些输送平台不仅必须针对单个肿瘤细胞成分，还需要安全、高效和可扩展的生产。在此，我们综述了最近的针对肿瘤微环境 (TME) 中各个成分的创新靶向纳米颗粒输送策略，包括与癌症相关的血液和淋巴血管、周细胞、肿瘤相关成纤维细胞和肿瘤干细胞。与促进广泛消融的传统疗法相反，新兴的纳米策略，如针对血管正常化的周细胞和内皮细胞的靶向治疗，正在被证明可以有效地将治疗药物递送到肿瘤中。此外，具有响应特定肿瘤微环境信号的可转换特性的新型智能靶向 NPs ，在细胞靶向和治疗释放方面展示了增强的时空控制能力。然而，将这些疗法转化为临床应用需要克服几个重大障碍，例如在动物模型中无法重现人类 TME 以及 NP 靶向疗效、安全性和可扩展性生产方面的问题。我们讨论了克服这些挑战的最新进展以及降低脱靶毒性的创新方法。我们还强调了当前 NP 开发中的重要缺陷，并就设计临床试验提供了新的观点，以加速靶向 NP 平台的临床转化。
