Biodegradable organosilica magnetic micelles for magnetically targeted MRI and GSH-triggered tumor chemotherapy.

Recently, block copolymer micelles have attracted widespread attention due to their controlled biodegradability and excellent loading capability. Unfortunately, the poor in vivo stability and low delivery efficiency of drug-loaded micelles greatly hampered their biomedical applications. Herein, we develop a new kind of biodegradable magnetite/doxorubicin (Fe3O4/DOX) co-loaded PEGylated organosilica micelles (designated as FDPOMs) with both high circulating stability and smart GSH-triggered biodegradability for magnetically targeted magnetic resonance imaging (MRI) and tumor chemotherapy. The FDPOMs are prepared by the self-assembly of biodegradable polycaprolactone-block-poly(glutamic acid) (PCL-b-PGA), a chemotherapeutic DOX drug and Fe3O4 nanoparticles in an oil/water system, subsequent organosilica cross-linking with 3-mercaptopropyltrimethoxysilane (MPTMS) molecules and surface PEGylation. The resultant FDPOMs exhibit excellent dispersity and stability in biological media, remarkable T2-weighted MR imaging capability, unique GSH-responsive release behavior and selective toxicity to tumor cells. The in vivo experiments show that the FDPOMs not only have improved MR tumor imaging capability, but also exhibit high anti-tumor efficacy due to the strong magnetic targeting ability under an external magnetic field. Consequently, the FDPOMs are promising candidates for magnetically targeted MR imaging and imaging-guided tumor chemotherapy.

A facile approach to fabricate functionalized superparamagnetic copolymer-silica nanocomposite spheres.

Novel amino- or thiol-functionalized superparamagnetic copolymer-silica nanospheres (NH2-SMCSNs/SH-SMCSNs), which consist of a magnetic core and a silica cross-linked block copolymer shell, have been fabricated.

Mesoporous manganese silicate coated silica nanoparticles as multi-stimuli-responsive T1-MRI contrast agents and drug delivery carriers.

A novel kind of monodisperse mesoporous manganese silicate coated silica nanoparticle (MMSSN) as a highly efficient T1-weighted MRI contrast agent (CA) and drug carrier for cancer diagnosis and chemotherapy has been constructed by a modified "SiO2 sacrifice and in situ silicate growth" approach under a relatively low hydrothermal temperature and alkali-free condition. The mesoporous manganese silicate shell provides a large specific surface area and abundant exposed Mn paramagnetic centers to water molecules, which endows the MMSSNs with extraordinarily high longitudinal relaxivity. Meanwhile, the MMSSNs presented an efficient pH/redox-responsive T1-MRI feature based on the significant enhancement of relaxation rate (r1) stimulated by mild acidic environment or reducing agent (GSH) both in vitro and in vivo. Furthermore, the mesoporous structure and negatively charged pore surface of the manganese silicate shell enable the MMSSNs to attain anti-cancer drug (DOX) storage and a pH-responsive release, which is suitable for on-demand drug release for the chemotherapy of tumors. Therefore, the mesoporous manganese silicate-based nanomaterial is a promising candidate as T1-MRI CAs and anticancer-drug delivery carriers for the theranostics of tumor in an intelligent and on-demand manner. STATEMENT OF SIGNIFICANCE: MRI is one of the most frequently used imaging techniques in daily clinics for cancer diagnosis. Using contrast agents (CAs) in MRI can afford much clearer and enlarged images of detectable organs. Gadolinium (Gd(3+))-based T1-positive CAs are widely used but associated with the risk of nephrogenic systemic fibrosis. To achieve much safer CAs, various Mn(2+)-based T1-positive CAs have been reported, such as MnO or core-shell MnOx-based nanoparticles. However, the efficiency of these CAs is still lower. Herein, we report a novel kind of mesoporous manganese silicate coated silica nanoparticle as CA and anti-cancer drug carrier. Results obtained from this study, especially the pH/redox-responsive T1-MRI feature are helpful for us to further design efficient MnSiO3-based materials for clinical MRI applications.

A pH-responsive hybrid fluorescent nanoprober for real time cell labeling and endocytosis tracking.

Hydrophilic, fluorescent hybrid nanoprobes (NDI@HNPs) encapsulated with the hydrophobic pH-responsive fluorophore (N,N'-di-n-dodecyl-2,6-di(4-methyl-piperazin-1-yl)naphthalene-1,4,5,8-tetracarboxylic acid diimide, NDI) for recognizing and mapping the route of cell phagocytosis have been fabricated based on the self-assembly of amphiphilic diblock copolymer PS-b-PAA and the subsequent shell cross-linking with 3-mercaptopropyltrimethoxy silane (MPTMS). The as-synthesized NDI@HNPs has a typical spherical morphology of 46 nm in diameter with excellent monodispersity in aqueous solution. The NDI@HNPs probe exhibits extremely low cytotoxicity, fast real time pH response and enhanced fluorescence intensity under acidic environment with respect to the corresponding free dye in highly polar aqueous system because of the encapsulation of NDI molecules inside nanoparticle cores with weak polarity environment. The fluorescence intensity of NDI@HNPs is enhanced by 55-fold upon changing from neutral (pH = 7.4) or basic (pH = 8.4) to acid (pH = 3.4) in aqueous system, in contrast to the serious fluorescence quenching of free NDI in the same medium, which can exactly meet the physiological pH range in cells. The favorably long emission wavelength is beneficial to the low scattering and minimal interfering requirements to fluorescent bioimaging. Moreover, functionalization with rapid cell-penetrating peptides (HIV-1 TAT) allows them to overcome the physiological and biological barriers during the phagocytosis process. Its characteristic fluorescent response to pH benefits the intracellular labeling and organelle targeting, realizing the real time tracking of the probe entry into cancer cells, the accumulation into the endolysosome and the further escape.