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Herein, a pH\/ROS dual-responsive nanogel (PRNG) was constructed by forming dynamic boronic ester crosslinkers between PEGylated hyaluronic acid bearing diethylenetriamine-grafted-catechol groups (PEG-HA-Dien-CA) and hyaluronic acid-conjugated phenylboronic acid (HA-PBA) for cytoplasmic cytochrome c (CC) delivery. This pioneering conceptual design not only facilitates the formation of stable nanocarriers with a high CC loading capacity, but also presents a distinctive mechanism for dual-responsive protein release. Confocal imaging confirmed that CC-loaded PRNG was efficiently internalized by A549 cells through CD44-dependent endocytosis, rapidly released from the endo\/lysosomal compartments, and effectively delivered CC into the cytoplasm, and subsequently induced cell apoptosis in the acidic tumor microenvironment (TME) rich in H2O2. 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