Chauhan Abhishek, Kamal Raj, Bhatia Rohit, Singh Thakur Gurjeet, Awasthi Ankit
Department of Pharmaceutics, ISF College of Pharmacy, Moga, 142001, Punjab, India.
School of Pharmacy, Desh Bhagat University, 147301, Punjab, India, Mandi Gobindgarh.
AAPS PharmSciTech. 2024 Dec 13;26(1):10. doi: 10.1208/s12249-024-03011-5.
Reactive oxygen species (ROS) play a dual role in cancer, acting as both signaling molecules that promote tumour growth and as agents that can inhibit tumour progression through cytotoxic effects. In cancer therapy, ROS-responsive drug delivery systems take advantage of the elevated ROS levels found in tumors compared to healthy tissues. These systems are engineered to release drugs precisely in response to increased ROS levels in tumour cells, allowing targeted and controlled treatment, minimizing side effects, and enhancing therapeutic outcomes. ROS generation in cancer cells is linked to metabolic changes, mitochondrial dysfunction, and oncogenic signaling, leading to increased oxidative stress. Tumour cells manage this by upregulating antioxidant defenses to prevent ROS from reaching harmful levels. This balance between ROS production and neutralization is critical for cancer cell survival, making ROS both a challenge and an opportunity for targeted therapies. ROS also connect inflammation and cancer. Chronic inflammation leads to elevated ROS, which can damage DNA and proteins, promoting mutations and cancer development. Additionally, ROS contribute to protein degradation, affecting essential cellular functions. Therapeutic strategies targeting ROS aim to either increase ROS beyond tolerable levels for cancer cells or inhibit their antioxidant defenses. Nanocarriers responsive to ROS show great potential in improving the precision of cancer treatments by releasing drugs specifically in high ROS environments, like tumors. This review discusses the mechanisms of ROS in cancer, its role in inflammation and protein degradation, and the advances in ROS-targeted nanocarrier therapies across different cancer types.
活性氧（ROS）在癌症中发挥着双重作用，既作为促进肿瘤生长的信号分子，又作为可通过细胞毒性作用抑制肿瘤进展的因子。在癌症治疗中，ROS响应性药物递送系统利用肿瘤组织中与健康组织相比升高的ROS水平。这些系统经过设计，能够精确地响应肿瘤细胞中ROS水平的升高而释放药物，实现靶向和可控治疗，将副作用降至最低，并提高治疗效果。癌细胞中的ROS生成与代谢变化、线粒体功能障碍和致癌信号传导有关，导致氧化应激增加。肿瘤细胞通过上调抗氧化防御机制来管理这一情况，以防止ROS达到有害水平。ROS产生与中和之间的这种平衡对于癌细胞的存活至关重要，这使得ROS既是靶向治疗的挑战，也是机遇。ROS还将炎症与癌症联系起来。慢性炎症会导致ROS升高，ROS可损害DNA和蛋白质，促进突变和癌症发展。此外，ROS有助于蛋白质降解，影响细胞的基本功能。针对ROS的治疗策略旨在要么将ROS增加到癌细胞无法耐受的水平，要么抑制其抗氧化防御机制。对ROS有响应的纳米载体通过在高ROS环境（如肿瘤）中特异性释放药物，在提高癌症治疗的精准度方面显示出巨大潜力。本文综述讨论了ROS在癌症中的作用机制、其在炎症和蛋白质降解中的作用，以及针对不同癌症类型的ROS靶向纳米载体疗法的进展。
