Semiconducting polymer nanoparticles (SPNs) have shown great promise in second near-infrared window (NIR-II) phototheranostics. However, the issue of long metabolic time significantly restricts the clinical application of SPNs. In this study, we rationally designed a biodegradable SPN (BSPN50) for NIR-II fluorescence imaging-guided photodynamic therapy (PDT). BSPN50 is prepared by encapsulating a biodegradable SP (BSP50) with an amphiphilic copolymer F-127. BSP50 is composed of NIR-II fluorescent diketopyrrolopyrrole (DPP) segment and degradable poly(phenylenevinylene) (PPV) segment with the ratio of 50/50. BSPN50 has both satisfactory degradability under myeloperoxidase (MPO)/hydrogen peroxide (H₂O₂) and NIR-II fluorescence emission upon 808 nm laser excitation. Furthermore, BSPN50 shows good photodynamic efficacy under 808 nm laser irradiation. BSPN50 shows a faster degradation rate than BSPN100 which has no PPV segment both in vitro and in vivo. In addition, BSPN50 can effectively diagnose tumor via NIR-II fluorescence imaging and inhibit the tumor growth by PDT. Thus, our study provides a rational approach to construct biodegradable nanoplatforms for efficient tumor NIR-II phototheranostics.

Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the oral and maxillofacial region. Due to its unique location, earlier and more accurate diagnosis and more minimally invasive treatment of OSCC is of major importance. Herein, gadolinium-containing semiconductor polymer nanoparticles (SPN-Gd) were designed and prepared. The nanoparticles consist of a near-infrared (NIR) absorption semiconductor polymer (PCPDTBT) served as fluorescence signal source and a photothermal conversion agent (PTA) and a gadolinium-grafted triblock amphiphilic copolymer (F127-DTPA-Gd) served as a magnetic resonance imaging (MRI) contrast agent and nanocarrier. The experiments in vivo showed that SPN-Gd could act as an MRI contrast agent and optical image agent with a long retention time, and it had a significant inhibiting effect on tumors of OSCC mice model through photothermal therapy (PTT). Thus our study provides a simple nanotheranostic platform composed of two components for efficient MR/fluorescence dual-modal imaging-guided PTT.