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Magnetic-, Acoustic-, and Optical-Triple-Responsive Microbubbles for Magnetic Hyperthermia and Pothotothermal Combination Cancer Therapy
Published on: May 22, 2020
A Novel Biodegradable Nanoplatform for Tumor Microenvironments Responsive Bimodal Magnetic Resonance Imaging and
Wanying Li1,2, Yinghui Wang1, Dongzhi Xue1,2
1State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry (CIAC), Chinese Academy of Sciences, Changchun 130022, China.
Abstract:
The unsatisfactory therapeutic effect and long-term adverse effect markedly prevent inorganic nanomaterials from clinical transformation. In light of this, we developed a novel biodegradable theranostic agent (MnCO3:Ho3+@DOX/Ca3(PO4)2@BSA, HMCDB) based on the sonosensitizer manganese carbonate (MnCO3) coating with calcium phosphate (Ca3(PO4)2) and simultaneously loaded it with the chemotherapeutic drug doxorubicin (DOX). Due to the mild acidity of the tumor microenvironment (TME), the Ca3(PO4)2 shell degraded first, releasing substantial quantities of calcium ions (Ca2+) and DOX. Meanwhile, with the ultrasound (US) irradiation, MnCO3 produced enough reactive oxygen species (ROS) to cause oxidative stress in the cells, resulting in accumulation of Ca2+. Consequently, the cascade effect significantly amplified the therapeutic effect. Importantly, the nanocomposite can be completely degraded and cleared from the body, demonstrating that it was a promising theranostic agent for tumor therapy. Furthermore, the doped holmium ions (Ho3+) and in situ generation of manganese ions (Mn2+) in TME endow the nanoagent with the ability for tumor-specific bimodality T1/T2-weighted magnetic resonance imaging (MRI). This novel nanoplatform with low toxicity and biodegradability holds great potential for cancer diagnosis and treatment.

