Manganese-Loaded Dual-Mesoporous Silica Spheres for Efficient T1- and T2-Weighted Dual Mode Magnetic Resonance Imaging

A novel class of manganese-based dual-mode contrast agents (DMCAs) based on the core–shell structured manganese-loaded dual-mesoporous silica spheres (Mn-DMSSs) for simultaneous T1- and T2-weighted magnetic resonance imaging (MRI) has been successfully reported. The in vitro MR tests demonstrate that the Mn-based DMCAs display an excellent simultaneous T1-weighted and T2-weighted MR imaging effect with a noticeably high T1 relaxivity (<i>r</i>₁) of 10.1 mM^–1s^–1 and a moderately high T2 relaxivity (<i>r</i>₂) of 169.7 mM^–1s^–1. The Mn-based DMCAs exhibit negligible cytotoxicity with >80% cell viability at a concentration of up to 200 μg/mL in human liver carcinoma (HepG2) and mouse macrophage (RAW264.7) cells after 24 h. Confocal laser scanning microscopy (CLSM) results show that the Mn-DMSSs were internalized via endocytosis and located in the cytoplasm but not in the nucleus. The in vivo experiment shows that the signals of rat liver increased by 29% under T1-weighted imaging mode and decreased by 28% under T2-weighted imaging mode in 5 min postinjection of Mn-DMSSs, which reveal that the novel Mn-loaded DMSSs can be used as both positive (T1-weighted) and negative (T2-weighted) MR contrast agents in further biomedical applications

Morphology Evolution and Spatially Selective Functionalization of Hierarchically Porous Silica Nanospheres for Improved Multidrug Delivery

Hierarchically porous materials are believed one of the most promising matrix materials due to their unique multimodal pore structures and great application potentials in catalysis, separation, and biomedicine. In this article, a series of hierarchically porous silica nanospheres with adjustable morphologies and pore structures/sizes has been successfully developed by controlling the electrostatic interaction-induced interfacial self-assembly behaviors between anionic block copolymer polystyrene-<i>b</i>-poly­(acrylic acid) (PS-<i>b</i>-PAA), cationic surfactant cetyltrimethylammonium bromide, and tetraethyl orthosilicate. Especially, “embedded” structured dual-mesoporous silica nanospheres (E-DMSNs) containing connected large mesopores (>10 nm) and abundant small mesopores (2–3 nm) in the large-pore framework have been prepared for the first time. Moreover, by employing PS-<i>b</i>-PAA with shorter PAA block lengths as template, the morphology conversion of porous silica nanospheres from core–shell structured dual-mesoporous silica nanospheres to well-defined hollow mesoporous silica nanospheres has been achieved. To endow the capability of E-DMSNs as multidrug delivery vehicles, a spatially selective functionalization strategy has been adopted to obtain dual-functionalized E-DMSNs (E-DMSNs-NH₂/OH) with amino-functionalized large mesopores and hydroxyl-modified small mesopores. Thermogravimetric-differential scanning calorimetry analysis shows that the loading amount of curcumin (Cur) and doxorubicin hydrochloride (DOX) were about 3.4% and 10.0% in weight, respectively. In addition, the cytotoxicity assay and cellular uptake of DOX@Cur@E-DMSNs-NH₂/OH on SMMC-7721 cells (human hepatoma cells) have been investigated. Thus, such a simple methodology to synthesize hierarchically porous silica with adjustable morphologies, pore sizes, and pore modifications provides a new pathway for the rational design of antitumor multidrug nanocarriers in further cancer treatment

Dual-Enzyme-Loaded Multifunctional Hybrid Nanogel System for Pathological Responsive Ultrasound Imaging and <i>T</i>₂‑Weighted Magnetic Resonance Imaging

A dual-enzyme-loaded multifunctional hybrid nanogel probe (SPIO@GCS/acryl/biotin-CAT/SOD-gel, or SGC) has been developed for dual-modality pathological responsive ultrasound (US) imaging and enhanced <i>T</i>₂-weighted magnetic resonance (MR) imaging. This probe is composed of functionalized superparamagnetic iron oxide particles, a dual enzyme species (catalase and superoxide dismutase), and a polysaccharide cationic polymer glycol chitosan gel. The dual-modality US/MR imaging capabilities of the hybrid nanogel for responsive US imaging and enhanced <i>T</i>₂-weighted MR imaging have been evaluated both <i>in vitro</i> and <i>in vivo</i>. These results show that the hybrid nanogel SGC can exhibit efficient dual-enzyme biocatalysis with pathological species for responsive US imaging. SGC also demonstrates increased accumulation in acidic environments for enhanced <i>T</i>₂-weighted MR imaging. Further research on these nanogel systems may lead to the development of more efficient US/MR contrast agents

Synthesis of a Pillar[5]arene-Based Polyrotaxane for Enhancing the Drug Loading Capacity of PCL-Based Supramolecular Amphiphile as an Excellent Drug Delivery Platform

A pillar[5]­arene-based nonionic polyrotaxane (PR) with <i>star</i>-poly­(ε-caprolactone) (<i>S</i>-PCL) as the axle, pillar[5]­arene (DEP5) as the wheel and adamantane as the end-capped group is designed and synthesized. The resulting PR is subsequently assembled with β-cyclodextrin end-capped pH-stimulated poly­(acrylic acid) (CD-PAA) via a host–guest interaction to form the supramolecular pseudoblock polymer PR-PAA. This supramolecular pseudoblock polymer could self-assemble in aqueous solution to produce PR-PAA-based supramolecular vesicular nanoparticles (PR-SVNPs), which present significantly enhanced drug loading capacity (DLC, 45.6%) of DOX, much higher than those of superamphiphiles (PCL-PAA, 17.1%). Such a high DLC of PR-SVNPs can be most probably attributed to the greatly decreased crystallinity of PCL in PR. Moreover, the loaded drugs could be selectively released in an acidic microenvironment-responsive manner. Compared to free DOX, the DOX-loaded PR-SVNPs (DOX@PR-SVNPs) shows much enhanced cellular uptake and cytotoxicity against the SMMC-7721. More importantly, thanks to the enhanced permeability and retention (EPR) effect, DOX@PR-SVNPs exhibits appealing features such as extremely low toxicity, highly efficient intratumoral accumulation and substantial antitumor efficacy in vivo