Albumin Encapsulationof Cyanine Dye for High-PerformanceNIR-II Imaging-Guided Photodynamic Therapy

Albumin encapsulation is a powerful strategy for drug delivery, yet its potential has not been fully explored for photodynamic therapy (PDT) agents. Cl-containing near-infrared (NIR) cyanine dyes are intrinsically PDT agents and tend to covalently bind with albumin; however, their PDT efficiency in tumors is largely compromised due to limited accumulation of the complex (size less than 10 nm) to the tumor site. To maximize their PDT effect while retaining sufficient NIR brightness for imaging-guided PDT, we developed a DTT-promoted encapsulation strategy to enhance singlet oxygen release for Cl-containing dyes. By disrupting disulfide bonds in albumin, the protein shell is loosened, increasing size while maintaining singlet oxygen release, partial brightness, and photostability. In vivo experiments reveal the rapid tumor accumulation of IR-6B3@DTT-HSA, enabling flexible treatment timing. This strategy enhances targeted delivery and PDT efficacy, paving the way for broader applications in cancer therapy.