Facile Access to Piezoelectric Polyamides by Polyamidation of Carboxylic Acids and Ynamides for Potent Tumor Immunotherapy.

Polyamides are a fascinating group of piezoelectric materials that are largely synthesized by the polycondesation of dicarboxylic acids with diamines or the ring-opening polymerization of special lactams. However, developing a green polymerization approach for the facile synthesis of piezoelectric polyamides is highly desirable but also challenging. Here, a simple polyamidation of carboxylic acids and ynamides is successfully established to synthesize versatile piezoelectric polyamides. This polymerization also possesses the merits of 100% atom economy, no waste generation, and additive-free as well as catalyst-free system. A range of polyamides are synthesized in moderate to good yields with satisfactory molecular weights. Importantly, piezoelectric polyamides containing tetraphenylethene (P1e/2b) can generate a bundant reactive oxygen species under ultrasound (US) exposure, thereby eliciting robust immunogenic cell death induction for augmented piezoelectric immunotherapy. Furthermore, P1e/2b exhibits distinctive aggregation-induced emission property that allows fluorescence imaging. In vivo evaluation using a bilateral tumor-bearing mouse model manifested that P1e/2b administration reinforced systemic immunity and triggered immune memory under US exposure, thereby leading to primary tumor eradication and distant tumor suppression. Therefore, this work represents a transition-metal-free and waste-free polymerization paradigm for the construction of piezoelectric polyamides, providing a distinct strategy to designing new piezoelectric polymers for effective tumor immunotherapy.