在病变部位精确激活聚合物纳米粒子对于实现良好的治疗效果至关重要。然而，传统内源性刺激响应型聚合物纳米粒子可能遭受刺激聚合物降解和后续功能的触发因子不足的问题。在这里，我们描述了含有苯硼酸酯和二茂铁作为重复骨架单元的氧化响应型聚（二茂铁）两性分子。当肿瘤细胞内的过氧化氢触发时，苯硼酸酯键断裂，聚（二茂铁）单元降解生成游离二茂铁和明显的氢氧根离子。释放的氢氧根离子可以立即改善聚（二茂铁）聚集物内的pH值，苯硼酸酯骨架的降解速率受到上调的pH的进一步促进；因此，加速的降解可以释放更多的附加氢氧根离子来改善pH，从而实现聚（二茂铁）聚集物的正向自我放大级联降解，伴随着氧化应激的增强和有效荷载释放。具体而言，当被H2O2触发时，聚（二茂铁）聚集物在12小时内可以降解到大约90％，而无二茂铁的对照纳米粒子在12天内只能降解30％。此外，水亲层上的马来酰亚胺基团可以捕获血清白蛋白形成富含白蛋白的蛋白质环境，并显著提高肿瘤的有利积累。目前的氧化响应型聚（二茂铁）两性分子能够在体外和体内有效抑制肿瘤。本研究为自我放大性聚合物降解和同时氧化应激提供了一个概念验证范例，有望在主动调节精确医学中发挥作用。

Precise activation of polymer nanoparticles at lesion sites is crucial to achieve favorable therapeutic efficacy. However, conventional endogenous stimuli-responsive polymer nanoparticles probably suffer from few triggers to stimulate the polymer degradation and subsequent functions. Here, we describe oxidation-responsive poly(ferrocene) amphiphiles containing phenylboronic acid ester and ferrocene as the repeating backbone units. Upon triggering by hydrogen peroxide inside the tumor cells, the phenylboronic acid ester bonds are broken and poly(ferrocene) units are degraded to afford free ferrocene and noticeable hydroxide ions. The released hydroxide ions can immediately improve the pH value within the poly(ferrocene) aggregates, and the degradation rate of the phenylboronic acid ester backbone is further promoted by the upregulated pH; thereupon, the accelerated degradation can release much more additional hydroxide ions to improve the pH, thus achieving a positive self-amplified cascade degradation of poly(ferrocene) aggregates accompanied by oxidative stress boosting and efficient cargo release. Specifically, the poly(ferrocene) aggregates can be degraded up to ∼90% within 12 h when triggered by H2O2, while ferrocene-free control nanoparticles are degraded by only 30% within 12 days. In addition, the maleimide moieties tethered in the hydrophilic corona can capture blood albumin to form an albumin-rich protein corona and significantly improve favorable tumor accumulation. The current oxidation-responsive poly(ferrocene) amphiphiles can efficiently inhibit tumors in vitro and in vivo. This work provides a proof-of-concept paradigm for self-amplified polymer degradation and concurrent oxidative stress, which is promising in actively regulated precision medicine.