Thiol–acrylate Michael addition strategy for the templated synthesis of a water-soluble poly(β-thioester) nanogel: superior encapsulation stability and UV-induced photolysis-mediated on-demand guest release

thiol-acrylate Michael addition click chemistry. This strategy generates multiple acid-labile β-thioester linkages within the core, enabling stable encapsulation of hydrophobic guest molecules. Notably, a five-fold reduction in guest leakage was achieved, highlighting the effectiveness of the core-crosslinking strategy, and the enhanced encapsulation stability was further confirmed by a Förster resonance energy transfer (FRET) study. The resulting core-cross-linked nanogel exhibits dual-stimuli responsive degradation governed by acidic pH and UV-light exposure, arising from β-thioester hydrolysis and photo-triggered cleavage of the BMTNB moiety, respectively. Guest-release studies reveal quantitative release under acidic conditions (pH 5.3) and light-intensity-dependent, on-demand release behavior that can be precisely modulated by adjusting the photon flux. Periodic UV irradiation experiments further demonstrate spatiotemporal control over guest release. Importantly, surface charge modulation under mildly acidic tumor extracellular conditions (pH ∼6.4-6.8) is expected to enhance cellular internalization, underscoring the potential of this robust and tunable nanoplatform for tumor-microenvironment-responsive drug delivery.