Merging Metal Organic Framework with Hollow Organosilica Nanoparticles as a Versatile Nanoplatform for Cancer Theranostics.

With great potential in nanomedicine, the integration of a metal organic framework (MOF) with a nanocarrier for smart and versatile cancer theranostics still seeks to expand. In this study, MOF was successfully merged with hollow mesoporous organosilica nanoparticles (HMONs) with a polydopamine (PDA) interlayer to form molecularly organic/inorganic hybridized nanocomposites (HMONs-PMOF). The well-defined nanostructure and favorable biocompatibility of HMONs-PMOF were demonstrated first. Doxorubicin hydrochloride (DOX) and indocyanine green (ICG) were separately loaded into the interior cavity of HMONs and the outer porous shell of MOF with high loading efficacy, respectively. The obtained dual drug-loaded nanocomposites (DI@HMONs-PMOF) displayed favorable photothermal properties and pH/NIR-triggered DOX release manner. Furthermore, in vitro cell experiments validated that HMONs-PMOF can efficiently deliver DOX into cancer cells. Upon entry into cancer cells, the photothermal effect of DI@HMONs-PMOF can induce the lysosome rupture, thereby facilitating the "lysosome escape" process and accelerating the DOX diffusion in the cytoplasm. Benefiting from the iron ion coordinated on PDA and ICG confined in MOF, magnetic resonance (MR) imaging and photoacoustic (PA) dual-modality imaging were performed to verify the effective accumulation of DI@HMONs-PMOF at the tumor site. Interestingly, the results also suggested that the existence of ICG can cooperatively enhance the MR imaging capability of prepared nanocomposites. In addition, the significantly improved synergistic therapeutic efficacy was confirmed both in vitro and in vivo. Thus, our results indicated that the merged nanostructure of HMONs and MOF is promising for versatile cancer theranostics. STATEMENT OF SIGNIFICANCE: Metal organic framework (MOF) has recently emerged as a class of fascinating nanocarriers. The integration of MOF with other nanostructures can endow the new nanoformulation with collective functionality and synergistic performance that are not accessed from single-component nanostructure. Herein, we reported the successful merging of MOF and hollow mesoporous organosilica nanoparticles (HMONs) to form a hollow nanocontainer with a well-defined nanostructure. The large cavity of HMONs and highly porous network of MOF enable high drug loading efficacy. Moreover, the dual-modality magnetic resonance and photoacoustic imaging can be realized, which is also benefited from the merged nanostructure. Overall, we expected this paradigm could pave way for integrating MOF with other nanocarriers to achieve more diverse applications.