In 2015, oncolytic virotherapy was approved for clinical use, and in 2017, recombinant adeno-associated virus (AAV) delivery was also approved. However, systemic administration remains challenging due to the limited number of viruses that successfully reach the target site. Although the US Food and Drug Administration (FDA) permits the use of higher doses of AAV to achieve greater rates of transduction, most AAV still accumulates in the liver, potentially leading to toxicity there and elsewhere. Targeting the tumor microenvironment is a promising strategy for cancer treatment due to the critical role of the tumor microenvironment in controlling tumor progression and influencing the response to therapies. Newly discovered evidence indicates that administration routes focusing on the tumor microenvironment can promote delivery specificity and transduction efficacy within the tumor. Here, we review approaches that involve modifying viral surface features, modulating the immune system, and targeting the physicochemical characteristics in tumor microenvironment to regulate therapeutic delivery. Targeting tumor acidosis presents advantages that can be leveraged to enhance virotherapy outcomes and to develop new therapeutic approaches that can be integrated with standard treatments.

2015年，溶瘤病毒疗法被批准用于临床，2017年，重组腺相关病毒（AAV）递送也被批准。然而，由于成功到达目标位点的病毒数量有限，全身给药仍然具有挑战性。尽管美国食品和药物管理局 (FDA) 允许使用更高剂量的 AAV 来实现更高的转导率，但大多数 AAV 仍然在肝脏中积聚，可能导致肝脏和其他地方的毒性。由于肿瘤微环境在控制肿瘤进展和影响治疗反应方面发挥着关键作用，因此靶向肿瘤微环境是一种有前途的癌症治疗策略。新发现的证据表明，专注于肿瘤微环境的给药途径可以促进肿瘤内的递送特异性和转导功效。在这里，我们回顾了涉及修饰病毒表面特征、调节免疫系统以及针对肿瘤微环境中的理化特征来调节治疗递送的方法。针对肿瘤酸中毒具有可用于增强病毒治疗效果并开发可与标准治疗相结合的新治疗方法的优势。