Sensitive CTC analysis and dual-mode MRI/FL diagnosis based on a magnetic core-shell aptasensor.

Synergizing the sensitive circulating tumor cell (CTC) capture, detection, release and the specific magnetic resonance/fluorescence (MR/FL) imaging for accurate cancer diagnosis is of great importance for cancer treatment. Herein, EcoR1-responsive complementary pairing of two ssDNA with a fluorescent P0 aptamer, which can specifically bind with the overexpressed MUC1 protein on cancer cells, was covalently modified to SiO2@C-coated magnetic nanoparticles for preparing a special nanoparticle-mediated FL turn-on aptasensor (FSC-D-P0). This aptasensor can selectively capture/enrich CTC and thus achieve sensitive CTC detection/imaging in even the blood due to its stable targeting, unique magnetic properties and the regulated interactions between the quencher and the fluorescent groups. Meanwhile, FSC-D-P0 can release the captured CTC for further downstream analysis upon the EcoR1 enzyme-triggered cleavage of the double-stranded DNA (dsDNA). Most importantly, this aptasensor can distinctly avoid false positivity of MRI via multiple targeting mechanisms. Thus, the sensitive CTC capture, detection, release and accurate MR/FL imaging were synergistically combined into a single platform with good biocompatibility, promising a robust pattern for clinical tumor diagnosis in vitro and in vivo.

Multifunctional mesoporous black phosphorus-based nanosheet for enhanced tumor-targeted combined therapy with biodegradation-mediated metastasis inhibition.

Functionalizing black phosphorus nanosheet (BP) with efficient drug loading and endowing mesoporous silica nanomaterials with appropriate biodegradation for controllable tumor-targeted chemo-photothermal therapy are still urgent challenges. Herein, an ordered mesoporous silica-sandwiched black phosphorus nanosheet (BP@MS) with the vertical pore coating was prepared. The strategy could not only enhance the BP's dispersity and improve its doxorubicin (DOX)-loading efficiency, but also facilitate post-modification such as PEGylation and conjugation of targeting ligand, TKD peptide, yielding BSPT. A DOX-loaded BSPT-based system (BSPTD) showed heat-stimulative, pH-responsive, and sustained release manners. In vitro and in vivo results demonstrated that BSPTD had a delayed but finally complete degradation in physiological medium, contributing to an optimal therapeutic window and good biosafety. As a result, BSPTD can achieve an effective chemo-photothermal synergistic targeted therapy of tumor. Moreover, treating by BSPTD was found to be capable of remarkably inhibiting the lung metastasis of tumor, attributing to the photothermal degradation-facilitated secondary drug delivery. Our study provided a robust strategy to functionalize BP nanosheet and biodegrade the mesoporous silica for extended biomedical applications.

Biodegradable Mesoporous Silica Achieved via Carbon Nanodots-Incorporated Framework Swelling for Debris-Mediated Photothermal Synergistic Immunotherapy.

Incorporating carbon nanodots (CDs) into mesoporous silica framework for extensive biomedicine, especially for the desirable cancer immunotherapy, is considered to be an unexplored challenge. Herein, a hydrogen bond/electrostatic-assisted co-assembly strategy was smartly exploited to uniformly incorporate polymer-coated CDs into ordered framework of mesoporous silica nanoparticles (CD@MSNs). The obtained CD@MSN was not only biodegradable via the framework-incorporated CD-induced swelling but also capable of gathering dispersive CDs with enhanced photothermal effect and elevated targeting accumulation, which therefore can achieve photothermal imaging-guided photothermal therapy (PTT) in vitro and in vivo. Interestingly, benefiting from the biodegraded debris, it was found that CD@MSN-mediated PTT can synergistically achieve immune-mediated inhibition of tumor metastasis via stimulating the proliferation and activation of natural killer cells and macrophages with simultaneously up-regulating the secretion of corresponding cytokines (IFN-γ and Granzyme B). This work proposed an unusual synthesis of biodegradable mesoporous silica and provided an innovative insight into the biodegradable nanoparticles-associated anticancer immunity.

Preparation and comparison of tacrolimus-loaded solid dispersion and self-microemulsifying drug delivery system by in vitro/in vivo evaluation.

This study aimed to compare the dissolution and the intestinal absorption of tacrolimus in self-microemulsifying drug delivery system (SMEDDS) and solid dispersion (SD). Poloxamer 188 SD was prepared by the combination of the solvent evaporation method and the freeze drying method. Hydroxypropyl methylcellulose (HPMC) SD was prepared by the solvent evaporation method combined with the vacuum drying method. The formation of SD was confirmed by SEM images which showed new solid phases. The SMEDDS was composed of oil (Labrafil M1944 CS 28%), surfactant (Cremophor EL 48%) and co-surfactant (Transcutol P 24%). The self microemulsion formed by the SMEDDS upon aqueous media had spherical droplets with a hydrodynamic size of 46.0±3.2nm. The dissolution of tacrolimus from SD and SMEDDS was performed in sink and non-sink conditions with various pH. As revealed by the DSC and FT-IR, the tacrolimus was molecularly or amorphously dispersed in the SMEDDS and SD. The in vivo intestinal absorption study in rats showed that both SMEDDS and SD improved the absorption of tacrolimus over the raw tacrolimus while the SMEDDS exhibited lower absorption rate constant (Ka) and apparent permeability coefficients (Papp) than the SD. The self-prepared SD with poloxamer 188 or HPMC had comparable intestinal absorption as compared with Prograf®. The tacrolimus-loaded SMEDDS and SD would be further compared by in vivo pharmacokinetic study.