Photosensitizer-Free Nanophosphor-Based theranostic probe for controllable photodynamic and photothermal visualization therapy

Photodynamic therapy (PDT) has emerged as a powerful candidate for cancer intervention as for the merits of least-invasiveness, multidrug resistance-free and spatiotemporal selectivity. Whereas, clinical photosensitizers (PSs) suffer from microsecond-level reactive oxygen species (ROS) lifetime requiring 20–30 min continuous exterior light stimulation, deficient photostable nature and off-target phototoxicity in nonmalignant tissues. Persistent luminescence nanoparticles (PLNPs), are proven to exert long-lasting ROS production after the excitation cessation (hours to days), and serve as photostable imaging agent for diagnose. Herein, a traceable theranostic agent, ZP@PCM PLNPs is prepared by modifying polyaniline (PANI) onto Zn1.2Ga1.6Ge0.2O4: Cr3+ (ZGGC) to obtain ZP PLNPs and wrapping phase-change material (PCM) as outer protective shell. Solid-phase PCM isolates inner ZP PLNPs from surrounding oxygen during circulation to circumvent off-target photosensitization. Once ZP@PCM PLNPs accumulated within tumors, external laser triggered PANI assisted photothermal therapy (PTT) initiates, and thermal melting of PCM shell occurs leading to the exposure of ZP PLNPs to switch on PDT. PANI also facilitates PDT efficacy optimization, enabling ZP PLNPs of 2-fold ROS yield compared to ZGGC PLNPs, sustained up to 48 h upon 10 min of illumination. ZP@PCM PLNPs with long-term, moderate therapy modality presents ameliorated anti-tumor effect, achieving tumor inhibition rate of 92.2 % over that of ∼ 46 % with individual ZGGC PLNPs, and shows satisfactory biosafety without tissues damage or inflammatory response. Meanwhile, the autofluorescence-free visualization potency helps to self-report therapeutic outcomes and determine treatment duration. Overall, ZP@PCM PLNPs provide a promising PSs-free alternative candidate for finely controlled PDT/PTT and visualization tumor therapy.