Ultrafast charge-conversional nanocarrier for tumor-acidity-activated targeted drug elivery

Nanocarriers with tumor-acidity-activated charge-conversional ability are of particular interest for targeted drug delivery in the field of precision nanomedicine. Nevertheless, the key challenge of this strategy is the slowness of reversing the surface charge at the tumor tissue. As a proof-of-concept, we synthesized the amphiphilic triblock polymer poly(ethylene glycol)-block-poly(2-carboxyethylacrylate)-block-poly(2-azepaneethylmethacrylate) (PEG-b-PCEA-b-PAEMA) to prepare the cisplatin-loaded nanocarrier UCC-NP/Pt. The PAEMA block at the physiological pH values was hydrophobic, which formed the core of UCC-NP/Pt. In contrast, at the tumor acidity, the tertiary amine groups of PAEMA block rapidly protonated, resulting in the ultrafast charge conversion of UCC-NP/Pt within 10 s. Such ultrafast charge-conversional effect more efficiently enhanced tumor cell internalization of nanocarriers, thus achieving targeted drug delivery, which in turn exhibited superior anticancer efficacy even in the cisplatin-resistant cells. This approach provides new avenues for tumor-acidity-activated targeted drug delivery.