Intelligent Pore Switch of Hollow Mesoporous Organosilica Nanoparticles for High Contrast Magnetic Resonance Imaging and Tumor-Specific Chemotherapy.

Hollow mesoporous organosilica nanoparticles (HMONs) are widely considered as a promising drug nanocarrier, but the loaded drugs can easily leak from HMONs, resulting in the considerably decreased drug loading capacity and increased biosafety risk. This study reports the smart use of core/shell Fe3O4/Gd2O3 (FG) hybrid nanoparticles as a gatekeeper to block the pores of HMONs, which can yield an unreported large loading content (up to 20.4%) of DOX. The conjugation of RGD dimer (R2) onto the DOX-loaded HMON with FG capping (D@HMON@FG@R2) allowed for active tumor-targeted delivery. The aggregated FG in D@HMON@FG@R2 could darken the normal tissue surrounding the tumor due to the high r2 value (253.7 mM-1 s-1) and high r2/r1 ratio (19.13), and the intratumorally released FG as a result of reducibility-triggered HMON degradation could brighten the tumor because of the high r1 value (20.1 mM-1 s-1) and low r2/r1 ratio (7.01), which contributed to high contrast magnetic resonance imaging (MRI) for guiding highly efficient tumor-specific DOX release and chemotherapy.

Polymer Self-Assembled BMSCs with Cancer Tropism and Programmed Homing.

Targeted therapy can improve the accuracy of diagnosis and treatment in the field of cancer management. Cellular surface engineering can enhance cell functions via mounting functional molecules onto cellular membranes. A novel amphiphilic hyperbranched polymer (AHP) conjugated with oleic acid (OA) and tumor-targeted ligand folic acid (FA) is employed. The lipophilic chain can self-assemble and infuse with the cytomembrane of bone marrow mesenchymal stem cells (BMSCs) with the end of FA left on the outside for targeting. The polymer tailored BMSCs can enhance tumor tropism in gastric cancer. BMSCs are characterized by the low immunogenicity and tumor tropism, which makes them promising targeting carriers. Regarding the integrated advantages of these two vectors, it is demonstrated that the functional amphiphilic AHP-OA-FA enhances the tumor tropism of BMSCs. Flow cytometry, standard MTT assay, and wound-healing assay show that AHP-OA-FA has no influence on CD expression, proliferative capacity, and cell motility of BMSCs, respectively. Furthermore, in vitro transwell assay and ex vivo fluorescence image verify that AHP-OA-FA enhances tumor tropism of BMSCs compared to BMSCs and AHP-OA-Rhodamine B-BMSCs. Finally, histological analysis demonstrates that AHP-OA-FA causes no damage to major organs. The results of this study suggest that living BMSCs self-assembled with a polymer might be a promising vehicle for targeted delivery to cancer cells.