Sub-50 nm Supramolecular Nanohybrids with Active Targeting Corona for Image-Guided Solid Tumor Treatment and Metastasis Inhibition

Tumor metastasis is responsible for almost 90% of failure in cancer therapy and it is also the major cause of cancer-associated mortality due to poor vascularization. Herein, a sub-50 nm hybrid theranostic robust nanoplatform is developed via a template supramolecular strategy to achieve active targeting and deep penetration of primary tumors as well as metastatic tumors with poor vascular structures. Quantum dots (QDs) as a template are coordinated with lipoic acid (LA)-functionalized dendrimers for covalent loading of doxorubicin (DOX) and Arg-Gly-Asp (RGD) tripeptide-functionalized polyethylene glycol (PEG) for prolonging blood circulation and selectively targeting cancer cells. When the nanohybrid is internalized into tumor cells, DOX releases from the nanohybrid in acidic lysosomes and is translocated into nuclei for arresting cell cycles at the G2/M phase, leading to a remarkably therapeutic effect for both primary tumors and distant metastases in a 4T1 xenograft tumor model. The inherent fluorescence of QDs in the nanohybrid allows real-time monitoring of the therapeutic responses from primary and metastasis tumors. Hence, a facile strategy is demonstrated to construct a hybrid nanoplatform with multifunctionality for inhibition of both primary and metastatic cancer.