Excitation-modulated upconversion nanoprobes for switchable imaging and phototherapy

Cancer phototheranostics has emerged as a cornerstone of personalized precision medicine to achieve efficient and targeted tumor treatment. Upconversion nanoparticles (UCNPs)-mediated phototheranostics exhibited remarkable potential for imaging diagnostics and therapeutic applications. Nevertheless, integrating programmable photoactivation functions of imaging and therapy within a single UCNP with negligible phototoxicity remains a huge challenge, primarily due to the absence of precise photoswitching strategies. Herein, a pulse-responsive upconversion nanoagent (UCNA) is designed to enable imaging-guided precision phototherapy through tunable red/green emissions. The UCNA is constructed based on a UCNPs@mSiO₂ core–shell structure conjugated with photosensitizer (neutral red) and drug (curcumin), and gated by a β-cyclodextrin-adamantane (β-CD-AD) host–guest supramolecular complex. The red emission is utilized for determining the tumor area through fluorescence imaging under 980 nm laser irradiation with a long pulse width (LPW). By switching the laser duty cycle into a short pulse width (SPW) mode, the resultant green emission can active photosensitizer to produce cytotoxic singlet oxygen (¹O₂), and simultaneously trigger drug release for antitumor therapy. The results demonstrate the attractive performance of UCNP-mediated deep-tissue imaging and enhanced anti-tumor efficacy without obvious systemic toxicity. In general, this work provides a facile approach for tuning upconversion emission, thereby realizing the photoswitchable activation of imaging diagnostics and photodynamic therapeutics.