Programming a multiplex lanthanide nanoparticle for customized cancer treatment with real-time efficiency feedback

Abstract

Customized cancer therapy relies on timely therapeutic effect evaluation to provide prescription adjustment for individual cases. However, currently reported therapeutic reagents are rarely integrated with imaging probes for self-evaluation of effects. Contrast imaging agents to measure tumor size changes must be administrated separately after therapy, complicating the therapeutic process and delaying reporting time. Herein, we design a customized therapy platform (LNPs-RB/Pep/cRGD) by conjugating lanthanide nanoparticles (LNPs) with the photosensitizer rose bengal, a caspase-3 substrate peptide (with Cy7.5 labelled at the terminal), and the tumor-targeting molecule cRGD. LNPs exhibit NIR-IIb downconversion luminescence under 980 nm/808 nm excitations for in vivo imaging, and visible upconversion luminescence under high-power 980 nm excitation for photodynamic therapy (PDT). By sequentially programming NIR excitation wavelength and power, NIR-IIb-imaging guided PDT and real-time cancer cell apoptosis imaging are achieved as therapeutic efficiency feedback. PDT induces cell apoptosis, generating caspase-3, which cleaves Cy7.5-containing peptide fragments from LNPs. This process corresponds to a recovery in vivo of NIR-IIb ratiometric imaging at 808 nm versus 980 nm excitation. The cleaved Cy7.5-containing peptide fragment is cleared into urine for NIR imaging. Both cell apoptosis imaging processes are completed 12 h after PDT, which is 7 days earlier than tumor size measurement. Therefore, customized therapy is achieved by timely adjusting PDT dosage, enhancing therapeutic efficacy.