Overcoming biological barriers to imaging-guided site-specific delivery of therapeutics is the goal of current nanomedicine designs. Here, multifunctional polymer-coated carbon nanodots with an interleukin-6 (IL-6) fragment peptide for receptor-targeting (pCDPI) were prepared for drug delivery. The pCDPI exhibits small hydrodynamic diameters, high water solubility and biocompatibility. In vitro and in vivo results demonstrated that pCDPI can overcome the blood-brain barrier (BBB) and deeply penetrate into orthotopic glioma in mice, to inhibit IL-6-induced cell proliferation and achieve imaging-guided targeted drug delivery. Simultaneously, a pH-sensitive sustained release of doxorubicin (DOX) accompanied with real-time fluorescence monitoring was realized. A distinct synergistic therapeutic outcome could be achieved which suggests the presented nanomedicine having promising potential for future cancer treatments.

The effective treatment of glioma is largely hindered by the poor transfer of drug delivery systems across the blood-brain barrier (BBB) and the difficulty in distinguishing healthy and tumorous cells. In this work, for the first time, an interleukin-6 receptor binding I6P7 peptide was exploited as a cascade-targeting ligand in combination with a succinoyl tetraethylene pentamine (Stp)-histidine oligomer-based nonviral gene delivery system (I6P7-Stp-His/DNA). The I6P7 peptide provides multiple functions, including the cascade-targeting potential represented by a combined BBB-crossing and subsequent glioma-targeting ability, as well as a direct tumor-inhibiting effect. I6P7-Stp-His/DNA nanoparticles (NPs) mediated higher gene expression in human glioma U87 cells than in healthy human astrocytes and a deeper penetration into glioma spheroids than scrambled peptide-modified NPs. Transport of I6P7-modified, but not the control, NPs across the BBB was demonstrated in vitro in a transwell bEnd.3 cell model resulting in transfection of underlying U87 cells and also in vivo in glioma-bearing mice. Intravenous administration of I6P7-Stp-His/plasmid DNA (pDNA)-encoding inhibitor of growth 4 (pING4) significantly prolonged the survival time of orthotopic U87 glioma-bearing mice. The results denote that I6P7 peptide is a roborant cascade-targeting ligand, and I6P7-modified NPs might be exploited for efficient glioma therapy.Download high-res image (239KB)Download full-size image

A facile one-step solvothermal method was developed for the homogeneously confined growth of ultra-small (∼1.5 nm) and monodispersed 2H phase MoS2 nanodots into mesoporous silica nanoparticles (MSNs).

Dispersed incorporation of functional nanoparticles into ordered mesopores to exert their synergistic properties has shown a promising application, but proved to be a challenging task. Herein, a facile strategy based on solid-phase transformation of the template into polymer-coated carbonaceous nanodots (pCNDs) is used for direct synthesis of multifunctional mesoporous silica nanospheres (MFMSNs) incorporated with dispersed fluorescent carbon nanodots. The homogeneous pCNDs incorporated into mesoporous silica nanospheres (MSNs) can simultaneously act as the nontoxic fluorescence probe for highly efficient fluorescence imaging and also anchoring sites for anticancer drug loading. On the basis of the special hydrophobic π–π/electrostatic interaction between the confined pCNDs in MFMSNs and the aromatic drug molecules, MFMSNs could also function as an advanced drug carrier for pH-triggered drug release. The very simple strategy suggests new insights for synthesizing multifunctional mesoporous nanomaterials and extends the biomedical functions of traditional MSN-based nanovehicles for future biomedical applications.

Multiple diagnosis of cancer by a facile fluorescent sensor is extremely attractive. Herein, a Cy3-labeled ssDNA probe (P0-Cy3) was π–π stacked on the surface of oxidized mesoporous carbon nanospheres (OMCN) to construct the fluorescent “turn-on” aptasensor. Attributing to the intrinsic properties of OMCN, the OMCN-based aptasensor not only can be used to detect mucin1 protein in liquid with a wide range of 0.1–10.6 μmol/L, a low detection limit of 6.52 nmol/L, and good selectivity, but also can quantify the cancer cells in solution with the linear range of 104–2 × 106 cells/mL and a detection limit of 8500 cells/mL. Fascinatingly, this OMCN-based aptasensor was exploited to image cancer via solid tissues such as cells, tissue sections, and ex vivo and in vivo tumors, in which the obvious distinguishability between cancer and normal tissues was clearly demonstrated. This is a robust and simple detection technique, which can well achieve the multiple diagnosis of cancer in vitro and in vivo.Keywords: aptasensor; fluorescent imaging; mesoropous carbon nanospheres; mucin1; multiple diagnosis;

Tumor site-directed multifunctional therapeutic platforms such as photothermochemotherapy that respond to tumor-focused physical and biological stimuli are highly demanded for effective cancer therapy. Herein, targeting peptide-conjugated core–shell graphitic carbon@silica nanospheres with dual-ordered mesopores (MMPS) were successfully fabricated and developed as antitumoral doxorubicin (DOX) delivery system (MMPSD) for synergistic targeted photothermal chemotherapy of breast cancer. The hydrophilic mesoporous silica shell guarantees good water dispersity of MMPSD. The hydrophobic graphitic mesoporous carbon core provides excellent hydrophobic drug loading, immediate contact between the drug and photothermal hotspots, and high NIR photothermal conversion efficiency. SP13 peptide facilitates MMPSD for targeted and enhanced delivery of DOX within HER2-positive SK-BR-3 breast cancer cells, while PEGylation ensures biocompatibility. Thus, the MMPSD system exhibited efficient drug loading capacity, high targeting ability, sensitive NIR/pH-responsive DOX release, sustained release, and excellent combined antitumor activity.Keywords: combined therapy; core−shell; mesoporous carbon; mesoporous silica; targeted delivery

Current therapy of malignant glioma in clinic is unsatisfactory with poor patient compliance due to low therapeutic efficiency and strong systemic side effects. Herein, we combined chemo-photothermal targeted therapy of glioma within one novel multifunctional drug delivery system. A targeting peptide (IP)-modified mesoporous silica-coated graphene nanosheet (GSPI) was successfully synthesized and characterized, and first introduced to the drug delivery field. A doxorubicin (DOX)-loaded GSPI-based system (GSPID) showed heat-stimulative, pH-responsive, and sustained release properties. Cytotoxicity experiments demonstrated that combined therapy mediated the highest rate of death of glioma cells compared to that of single chemotherapy or photothermal therapy. Furthermore, the IP modification could significantly enhance the accumulation of GSPID within glioma cells. These findings provided an excellent drug delivery system for combined therapy of glioma due to the advanced chemo-photothermal synergistic targeted therapy and good drug release properties of GSPID, which could effectively avoid frequent and invasive dosing and improve patient compliance.

A facile one-step solvothermal method was developed for the homogeneously confined growth of ultra-small (∼1.5 nm) and monodispersed 2H phase MoS2 nanodots into mesoporous silica nanoparticles (MSNs).