Then, the potential of PTX-NB for in vitro release of chemotherapeutic agents was examined. To develop a hypoxia-activated prodrug, the chemotherapeutic agent PTX was designed to link with 4-nitrobenzyl chloroformate to produce PTX-NB. As depicted in Figure , it was anticipated that PTX-NB would undergo reduction in a hypoxic environment, leading to the formation of an unstable amine intermediate and subsequent spontaneous selfelimination to release active PTX. The synthesis and characterization of the PTX-NB prodrug were detailed in the supplementary information (Scheme S2). The 1 H NMR spectra of PTX and PTX-NB confirmed the accurate chemical structure of the prodrug (Figure and Figure ). To assess the hypoxia activated capacity of the prodrug, PTX-NB was subjected to different concentrations of sodium dithionite (Na2S2O4) solution to simulate hypoxic conditions. The reaction system was then analyzed using high-performance liquid chromatography (HPLC). As depicted in Figure ). Hematoxylin and eosin (H&E) staining was performed on tumors and major organs in each group to investigate potential systemic toxicity. As shown in Figure and Figure , no evident damage or inflammatory lesions were observed in the heart, liver, spleen, lung, and kidney. However, the PTX, TPE-Pyα-CD + light, TPE-Pyα-CD + PTX-NB + light groups exhibited significant necrosis of the cell nucleus. Furthermore, blood routine assays were carried out on all groups after 7 days of treatment, revealing minimal variations in the hematological indexes as shown in Table . This further demonstrates the excellent antitumor activity and low systemic toxicity.