Magnetic Manganese Oxide Sweetgum-Ball Nanospheres with Large Mesopores Regulate Tumor Microenvironments for Enhanced Tumor Nanotheranostics

An important objective of cancer nanomedicine is to improve the delivery efficacy of functional agents to solid tumors for effective cancer imaging and therapy. Stimulus-responsive nanoplatforms can target and regulate the tumor microenvironment (TME) for the optimization of cancer theranostics. Here, we developed magnetic manganese oxide sweetgum-ball nanospheres (MMOSs) with large mesopores as tools for improved cancer theranostics. MMOSs contain magnetic iron oxide nanoparticles and mesoporous manganese oxide (MnO2) nanosheets, which are assembled into gumball-like structures on magnetic iron oxides. The large mesopores of MMOSs are suited for cargo loading with chlorin e6 (Ce6) and doxorubicin (DOX), thus producing so-called CD@MMOSs. The core of magnetic iron oxides could achieve magnetic targeting of tumors under a magnetic field (0.25 mT), and the targeted CD@MMOSs may decompose under TME conditions, thereby releasing loaded cargo molecules and reacting with endogenous hydrogen peroxide (H2O2) to generate oxygen (O2) and manganese (II) ions (Mn2+). Investigation in vivo in tumor-bearing mice models showed that the CD@MMOS nanoplatforms achieved TME-responsive cargo release, which might be applied in chemotherapy and photodynamic therapy. A remarkable in vivo synergy of diagnostic and therapeutic functionalities was achieved by the decomposition of CD@MMOSs and coadministration with chemo-photodynamic therapy of tumors using the magnetic targeting mechanism. Thus, the result of this study demonstrates the feasibility of smart nanotheranostics to achieve tumor-specific enhanced combination therapy.