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化疗作为恶性肿瘤临床治疗领域的主流手段，在当代肿瘤综合治疗体系中具有不可替代的临床价值。但是当前化疗药物存在以下关键局限性：首先，其理化性质表现为普遍水溶性不佳，且缺乏肿瘤组织靶向性；其次，在药代动力学方面存在系统清除快、生物利用度低的问题，同时伴随显著的毒性反应；更重要的是，长期化疗会诱导肿瘤细胞产生多药耐药性，这已成为导致化疗方案失效的首要机制。针对以上局限性，前药递送系统作为一种新型的解决方案应运而生。该递送策略通可以明显增强药物溶解性、延长血液半衰期、实现肿瘤靶向递送。而且该策略支持多药共载，实现协同治疗。这种多维度优化使得化疗疗效获得系统性提升。尽管前药递送系统提升了传统药物的利用率，但该系统也面临着难以向肿瘤深处渗透，细胞摄取困难以及药物释放不完全等弊端。为此，当前研究热点聚焦于智能响应型前药递送系统的开发并经过功能调控来实现精准给药：（1）在体循环阶段维持结构完整性，确保药物封装稳定性，保护药物不被漏释；（2）通过感知肿瘤微环境特征参数（pH、活性氧水平、生物酶表达水平等因素）引发结构改变，从而区分肿瘤组织和正常组织，并释放药物，降低对正常组织的毒副作用；（3）动态调控递送系统的理化性质（表面电荷分布、粒径尺寸、分子拓扑结构等），从而同步优化肿瘤组织渗透性、细胞摄取效率及可控制释放的药代动力学。这种智能响应型递送系统有效突破了传统化疗药物的生物屏障限制。本文回顾了智能响应型前药递送系统在肿瘤诊疗一体化研究中的进展，并对该领域的未来发展趋势做了展望。
Abstract：Chemotherapy, as the mainstream therapeutic modality in clinical oncology, remains clinically irreplaceable in the contemporary multimodal cancer management frameworks. However, current chemotherapeutic agents have the following critical limitations: Firstly, their physicochemical characteristic includes unfavorable aqueous solubility and inadequate tumor-specific targeting capabilities; secondly, pharmacokinetic limitations are revealed in accelerated systemic clearance and diminished bioavailability with marked cytotoxic sequelae. Notably, long-term chemotherapy triggers the development of multidrug-resistant phenotypes in malignant tumor, which has become the primary mechanism of the failure of chemotherapy. To overcome the clinical limitations of chemotherapeutic agents, prodrug delivery systems have emerged as an innovative solution. This delivery strategy increases aqueous solubility, extends half-life of plasma, realizes tumor-targeted accumulation and enables synergistic treatment by co-delivery of multi-drug. This multidimensional optimization leads to a systematic improvement in chemotherapy efficacy. Although prodrug delivery systems have improved the utilization rate of traditional drugs, they have some drawbacks such as the difficulty in deeper tumor penetration depth, the difficulty in cellular uptake, and the incomplete release of drug. Therefore, the current research focuses on the development of intelligent responsive prodrug delivery systems and the precise drug-delivery through functional regulation:(1) In the systemic circulation phase, maintaining structural integrity ensures drug encapsulation stability and prevents premature drug leakage;(2) Drug delivery systems can distinguish tumor tissues from normal tissues by sensing characteristic parameters of the tumor microenvironment, such as pH, reactive oxygen species and enzyme expression levels, thereby triggering structural transformations to release drugs and reduce toxicity toward normal tissues;(3) Dynamic regulation of the physicochemical properties of prodrug delivery systems(surface charge distribution, particle size, and molecular topology) enables simultaneous optimization of tumor tissue penetration, cellular uptake efficiency, and controlled-release pharmacokinetics. This intelligent responsive prodrug delivery systems effectively overcomes the biological barrier limitations of traditional chemotherapy drugs. This review systematically summarizes the advancements of intelligent responsive prodrug delivery systems in the theranostics of tumor and provides insights into the future development trends of this field.
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基本信息:
中图分类号:R730.5
引用信息:
[1]田杨,阴彩霞,陈春英.基于智能响应型前药递送系统的肿瘤诊疗一体化策略研究进展[J].新兴科学和技术趋势,2025,4(03):239-257.
基金信息:
国家自然科学基金(22325703;22377071)
2025-10-13
2025-10-13
2025-10-13