Acidic pH-triggered AIE nanoparticles covalently cross-linking for enhanced tumor imaging and photodynamic therapy

Abstract

The therapeutic effect of tumors heavily relies on the accumulation and retention of nanomaterials at the tumor site. In here, we developed two acidic pH-responsive protonated PCL-PAE-DBCO and PCL-PAE-N3 polymers, and synthesized an aggregation-induced emission (AIE) photosensitizer (named TETCN). By using the nano precipitation method, we prepared PPP-DBCO and PPP-N3 nanoparticles (NPs) by encapsulating TETCN with PCL-PEG and PCL-PAE, which was modified with dibenzocyclooctyne (DBCO) or azide (N3) groups. When PPP-DBCO and PPP-N3 were mixed, the PAE deprotonation at pH 7.4 pulled the bioorthogonal groups inside the NPs to prevent them from crosslinking. But, at pH 6.5, PAE pushed the bioorthogonal groups onto the surface of NPs due to protonation, resulting in bioorthogonal crosslinking of PPP-DBCO and PPP-N3. The in vivo results showed that the co-injection of PPP-DBCO and PPP-N3 significantly enhanced the enrichment and retention at the tumor site and showed enhanced photodynamic therapy (PDT) effect compared to PPP-DBCO or PPP-N3 alone. Therefore, the pH-responsive covalent crosslinking strategy based on AIE NPs proposed in this study may enrich related carrier materials and tumor treatment strategies.