Mitochondria-targeted magnetic gold nanoheterostructure for multi-modal imaging guided photothermal and photodynamic therapy of triple-negative breast cancer

摘要

Triple-negative breast cancer (TNBC) is a type of highly aggressive cancer that is hard to be cured by the commonly used chemotherapy, mainly due to the lack of effective tumor targeting ability of the current drugs and TNBC drug resistance. Therefore, development of novel strategies for precise and high-efficient therapy of TNBCs is urgently needed. In the present work, a multifunctional magnetic gold nanoheterostructure with photosensitizer Ce6 loading (MGN@Ce6) was designed and synthesized for synergistic photothermal and photodynamic therapy (PTT/PDT) of TNBC. To improve the tumor targeting ability, cRGD and TPP cationic molecule, which can specifically target alpha(v)beta(3) integrin of cancer cell membrane and mitochondria, respectively, were functionalized on the nanosystem obtaining MGN@Ce6@RT. In vitro and in vivo fluorescent imaging demonstrated that cRGD and TPP functionalization largely enhanced the delivery-efficiency of MGN@Ce6@RT into TNBC cells and tumors. Under 880 nm and 660 nm laser irradiations, MGN@Ce6@RT exhibited strong hyperthermia effect and ROS generating ability, which exerted a synergistic anti-TNBC effect by completely suppressed the tumor growth of the nude mice model. Moreover, by integrating superparamagnetic and near infrared light absorption properties into a single nanocomposite, MGN@Ce6@RT was proved to be able to realize magnetic resonance, X-ray computed tomography and photoacoustic tri-modal imaging of in vivo tumors. In all, we provide a novel strategy for precise delivery of functional nanosystems to TNBC tumors to achieve more satisfying treating outcome.