Multifunctional Gold Super‐Nanoparticle‐Based Nanosystem for SERS‐Guided Oxygen‐Independent Phototherapy

Cancer treatment remains a formidable challenge due to the complex and hypoxic microenvironment of tumors, which often compromises therapeutic efficacy. To address this issue, a multifunctional gold super-nanoparticle-based nanosystem (GSPs^1,4-BDT@PDA-AIPH-cRGD) was developed for surface-enhanced Raman scattering (SERS)-guided oxygen-independent phototherapy. This nanosystem integrates diagnostic and therapeutic functionalities through a gold superlattice-nanoparticle (GSP) core self-assembled from 5.8 nm gold nanoparticles (GNPs), functionalized with 1,4-benzenedithiol (1,4-BDT) as a Raman reporter. The GSPs are encapsulated with a polydopamine (PDA) shell for enhancing their structural stability, Raman signal amplification, and serving as a photothermal agent. The PDA coating layer is further loaded with 2,2'-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIPH), an oxygen-independent photosensitizer that releases cytotoxic free radicals, and cyclic arginine-glycine-aspartic acid (cRGD) peptide for tumor targeting. Under near-infrared (NIR) light irradiation, the nanosystem generates hyperthermia and releases free radicals, achieving oxygen-independent tumor ablation. Real-time SERS imaging ensures precise tumor monitoring, addressing key challenges in cancer management. This novel approach combines the benefits of highly sensitive SERS imaging, targeted drug delivery, and oxygen-independent phototherapy, providing a robust platform for synergistic cancer diagnosis and treatment with significant therapeutic potential.