The past few decades have seen great progress in the exploration of nanoparticles (NPs) as novel tools for cancer treatments and diagnosis. Practical and reliable application of nanoparticle-based technology in clinical transformation remains nevertheless an ongoing challenge. The design, preparation, and evaluation of various smart NPs with specific physicochemical responses in tumor-related physiological conditions have been of great interests in both academic and clinical research. Of particular, smart enzyme-responsive nanoparticles can predictively and selectively react with specific enzymes expressed in tumor tissues, leading to targeted delivery of anti-tumor drugs, reduced systemic toxicity, and improved therapeutic effect. In addition, NPs interact with internal enzymes usually under mild conditions (low temperature, aqueous media, neutral or close to neutral pH) with high efficiency. In this review, recent advances in the past 5 years in enzyme-responsive nanoparticles for anti-tumor drug delivery are summarized and discussed. The following contents are divided based on the different action sites of enzymes toward NPs, notably hydrophobic core, cleavable/uncleavable linker, hydrophilic crown, and targeting ligand. Enzyme-engaged destruction of any component of these delicate nanoparticle structures could result in either targeting drug delivery or controlled drug release.

在过去的几十年中，纳米粒子（NPs）作为癌症治疗和诊断的新工具的探索取得了长足的进步。然而，基于纳米颗粒的技术在临床转化中的实际和可靠应用仍然是一个持续的挑战。在肿瘤相关生理条件下具有特定理化反应的各种智能NP的设计，制备和评估在学术和临床研究中都引起了极大的兴趣。特别地，智能的酶反应性纳米颗粒可以与肿瘤组织中表达的特定酶进行预测性和选择性反应，从而导致抗肿瘤药物的靶向递送，降低的全身毒性和改善的治疗效果。此外，NP通常在温和的条件下（低温，水性介质，中性或接近中性的pH值）。在这篇综述中，总结并讨论了过去5年中用于抗肿瘤药物递送的酶反应性纳米颗粒的最新进展。根据酶对NP的不同作用位点划分以下内容，尤其是疏水核心，可裂解/不可裂解的接头，亲水冠和靶向配体。这些微妙的纳米颗粒结构中任何成分的酶促破坏都可能导致靶向药物递送或受控药物释放。尤其是疏水核，可裂解/不可裂解的接头，亲水冠和靶向配体。这些微妙的纳米颗粒结构中任何成分的酶促破坏都可能导致靶向药物递送或受控药物释放。尤其是疏水核，可裂解/不可裂解的接头，亲水冠和靶向配体。这些微妙的纳米颗粒结构中任何成分的酶促破坏都可能导致靶向药物递送或受控药物释放。