NIR-triggered photodynamic therapy of traumatic heterotopic ossification with a type II collagen-targeted photosensitizer

Traumatic heterotopic ossification (HO) represents an intractable sequela following trauma with no currently effective prophylaxis or treatment. Photodynamic therapy (PDT) is a non-invasive treatment for various proliferative diseases. However, the specific effects of PDT on HO development remain unclear. In this study, the therapeutic potential of a near-infrared (NIR) probe-WL-808, composed of type II collagen-binding peptide (WYRGRL) and a PDT photosensitizer (IR-808), was evaluated for the innovative HO-targeted PDT approach. In vitro studies indicated that WL-808 could induce chondrocyte apoptosis and inhibit cell viability through ROS generation under NIR excitation. In vivo, the efficacy of WL-808-mediated PDT was tested on the tenotomy HO model mice. WL-808 specifically targeted the type II collagen cartilaginous template of HO, promoting cell apoptosis and enhancing extracellular matrix (ECM) degradation under 808 nm NIR excitation, which inhibited the final ectopic bone formation. Moreover, no obvious toxicity or side effects were detected after treatment with WL-808. Taken together, WL-808-mediated PDT significantly diminished ectopic cartilage and subsequent bone formation, providing a new perspective for HO prophylaxis and treatment.