As an emerging and promising treatment method, gas therapy has attracted more and more attention for treatment of inflammation-related diseases, especially cancer. However, therapeutic/therapy-assisted gases (NO, CO, H2S, H2, O2, SO2 and CO2) and most of their prodrugs lack the abilities of active intratumoral accumulation and controlled gas release, resulting in limited cancer therapy efficacy and potential side effects. Therefore, development of nanomedicines to realize tumor-targeted and controlled release of therapeutic/therapy-assisted gases is greatly desired, and also the combination of other therapeutic modes with gas therapy by multifunctional nanocarrier platforms can augment cancer therapy efficacy and also reduce their side effects. The design of nanomedicines with these functions is vitally important, but challenging. In this review, we summarize a series of engineering strategies for construction of advanced gas-releasing nanomedicines from four aspects: (1) stimuli-responsive strategies for controlled gas release; (2) catalytic strategies for controlled gas release; (3) tumor-targeted gas delivery strategies; (4) multi-model combination strategies based on gas therapy. Moreover, we highlight current issues and gaps in knowledge, and envisage current trends and future prospects of advanced nanomedicines for gas therapy of cancer. This review aims to inspire and guide the engineering of advanced gas-releasing nanomedicines.
作为一种新兴且有前景的治疗方法，气体疗法在炎症相关疾病特别是癌症治疗领域受到越来越多的关注。然而，治疗性/辅助性气体（如一氧化氮、一氧化碳、硫化氢、氢气、氧气、二氧化硫和二氧化碳）及其大多数前药缺乏肿瘤内主动蓄积和可控释放的能力，导致癌症治疗效果有限并可能产生副作用。因此，亟需开发能够实现肿瘤靶向和可控释放治疗性/辅助性气体的纳米药物。同时，通过多功能纳米载体平台将气体疗法与其他治疗模式相结合，可增强癌症疗效并降低副作用。具备这些功能的纳米药物的设计至关重要，但也充满挑战。本综述从以下四个方面总结了构建先进释气纳米药物的工程策略：（1）可控气体释放的刺激响应性策略；（2）可控气体释放的催化策略；（3）肿瘤靶向气体递送策略；（4）基于气体疗法的多模式联合策略。此外，我们着重探讨了当前存在的问题与认知空白，并对癌症气体疗法先进纳米药物的当前趋势与未来前景进行展望。本综述旨在启发和指导先进释气纳米药物的工程化设计。
Strategies for engineering advanced nanomedicines for gas therapy of cancer
肿瘤(癌症)患者之家