Nanoscale-Coordination-Polymer-Shelled Manganese Dioxide Composite Nanoparticles: A Multistage Redox/pH/H2O2-Responsive Cancer Theranostic Nanoplatform
Jingjing Liu, Qian Chen, Wenwen Zhu, Xuan Yi, Yu Yang, Ziliang Dong, and Zhuang Liu*
Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-basedFunctional Materials and Devices, Soochow UniversitySuzhou, Jiangsu 215123, China
Nanoscale coordination polymers (NCPs) self-assembled from metal ions and organic bridging ligands exhibit many unique features promising for applications in nanomedicine. In this work, manganese dioxide (MnO2) nanoparticles stabilized by bovine serum albumin are encapsulated byNCP-shells constructed based on high-Z element hafnium (Hf) ions and c,c,t-(diamminedichlorodisuccinato)Pt(IV) (DSP), a cisplatin prodrug. After furthermodification with polyethylene glycol (PEG), the formed BM@NCP(DSP)-PEG can simultaneously serve as a radio-sensitizer owing to the strong X-ray attenuation capability of Hf to enhance radiotherapy, as well as a chemotherapeuticagent resulting from the reduction-induced release of cisplatin. Meanwhile, the in situ generated oxygen resulting from MnO2-triggered decomposition of tumor endogenous H2O2 will be greatly helpful for overcominghypoxia-associated radio-resistance. Upon intravenous injection, BM@NCP(DSP)-PEG shows efficient tumor homing as well as rapid renalexcretion, as illustrated by magnetic resonance imaging and confirmed by biodistribution measurement. Notably, an excellent in vivo tumor growthinhibition effect is observed with BM@NCP(DSP)-PEG nanoparticles after the combined chemoradiotherapy treatment. Therefore, the NCP-based compositenanoparticles with inherent biodegradability and no appreciable in vivotoxicity may be a unique type of multifunctional nanoplatform responsive to different parameters in the tumor microenvironment, promising for cancer theranostics with great efficacy.