Nanoscale-Coordination-Polymer-Shelled Manganese Dioxide Composite Nanoparticles: A Multistage Redox/pH/H2O2-Responsive Cancer Theranostic Nanoplatform

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 by NCP-shells constructed based on high-Z element hafnium (Hf) ions and c,c,t-(diamminedichlorodisuccinato)Pt(IV) (DSP), a cisplatin prodrug. After further modification 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 chemotherapeutic agent 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 overcoming hypoxia-associated radio-resistance. Upon intravenous injection, BM@NCP(DSP)-PEG shows efficient tumor homing as well as rapid renal excretion, as illustrated by magnetic resonance imaging and confirmed by biodistribution measurement. Notably, an excellent in vivo tumor growth inhibition effect is observed with BM@NCP(DSP)-PEG nanoparticles after the combined chemoradiotherapy treatment. Therefore, the NCP-based composite nanoparticles with inherent biodegradability and no appreciable in vivo toxicity may be a unique type of multifunctional nanoplatform responsive to different parameters in the tumor microenvironment, promising for cancer theranostics with great efficacy.