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 (GSPs1,4-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 is further loaded with 2,2'-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIPH), a 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.