NIR-II Fluorescence Imaging-Guided Combinatorial Therapy of Breast Cancer Using ICG/Chelerythrine-Loaded Aptamer-Targeted Liposomes.

Breast cancer remains a major global health challenge. Great efforts have been made to develop advanced theranostic platforms for breast cancer. A critical limitation of the current approaches is insufficient tumor accumulation. To address this, we developed AS1411 aptamer-functionalized liposomes coloaded with indocyanine green (ICG) and chelerythrine (I/C@Lipo-A) for enhanced breast cancer theranostics. ICG serves as a dual-functional agent, enabling deep-tissue fluorescence (FL) imaging in the second near-infrared (NIR-II, 1000-1700 nm) window and photothermal therapy (PTT). Leveraging ICG's superior tissue penetration and reduced scattering in the NIR-II window, this system significantly improves tumor delineation and therapeutic precision. Meanwhile, chelerythrine (CHE), a natural benzophenanthridine alkaloid with potent anticancer activity, induces mitochondrial dysfunction, apoptosis, and reactive oxygen species (ROS) generation. However, their clinical application has been hindered by poor solubility and bioavailability. By coencapsulating ICG and CHE within tumor-targeting liposomes, we synergistically enhanced CHE's anticancer efficacy while enabling NIR-II FL imaging-guided PTT. This combinatorial strategy not only suppressed primary tumor growth but also inhibited distant metastases, significantly improving survival rates. Our work presents a robust, multifunctional platform for precision breast cancer theranostics, overcoming key barriers in drug delivery and imaging-guided therapy.