Multifunctionalized Tumor-Triggered Targeting Theranostic Nanoparticles as a Precision NIR Imaging-Guided Nanoplatform for Photothermal/Photodynamic Therapy

Abstract

Suitable photosensitizers (PSs) are the prerequisite for effective imaging-guided phototherapy. However, traditional PSs have significant limitations, accompanied by unsatisfied tumor targeting ability, poor biocompatibility, and severe side effects. Herein, we report the design of an acid-activated near-infrared (NIR) probe and use it to construct an intelligent theranostic nanoplatform triggered by the tumor microenvironment for tumor-targeting image-guided photothermal and photodynamic therapy (PTT/PDT). First, acid-reversibly responsive brominated asymmetric cyanine 808 (BAC808) with a long-wavelength excitation (808 nm) is designed and synthesized as the tumor-specific NIR fluorescence/photothermal/photodynamic-in-one probe. It integrates acid-activated NIR fluorescence emission, outstanding photothermal conversion efficiency (42.68%), and high 1O2 generation ability (ΦΔ = 0.10), enabling effective PDT/PTT with minimized side effects. After encapsulating BAC808 and modification with a charge reversal group and tumor-targeting ligand simultaneously, the multifunctionalized tumor-triggered targeting theranostic nanoparticles (NPs) are fabricated with superior biocompatibility, long circulation time, and tumor-triggered targeting ability. The developed intelligent nanoplatform combines precise tumor targeting ability, specific imaging with a high signal-to-noise ratio, and excellent in vivo antitumor activity, making it a potential candidate for anticancer nanodrugs in practical applications.