A Biodegradable and pH-Sensitive Poly(β-amino ester) Nanoplatform for Tumor Imaging

Precise control of pH responsiveness is crucial for the design of smart nanomaterials in disease diagnosis and therapy. However, the nondegradable backbones of many existing systems hinder their clinical translation due to potential accumulation toxicity. Herein, we report a degradable and pH-sensitive nanoplatform (DPS) derived from poly(β-amino ester), enabling tunable pH transitions (pHt = 4.8–6.5) through systematic modulation of backbone and side-chain lengths. Upon fluorophore conjugation, DPS nanoprobes achieved up to 40-fold fluorescence activation within a narrow 0.4 pH window, allowing precise visualization of endosomal maturation from early endosomes to lysosomes. Moreover, the nanoprobes generated over 20-fold tumor-to-muscle signal ratios across multiple tumor models and enabled fluorescence-guided resection 24 h postinjection. Benefiting from its biodegradability nature, the DPS system demonstrated excellent biocompatibility, underscoring its potential as a safe and precisely tunable platform for next-generation tumor diagnostic and therapeutic nanomedicine.