Mesoporous silica nanoparticles functionalized by surface hyperbranching polymerization of poly(ethylene imine), PEI, were further modified by introducing both fluorescent and targeting moieties, with the aim of specifically targeting cancer cells. Owing to the high abundance of folate receptors in many cancer cells as compared to normal cells, folic acid was used as the targeting ligand. The internalization of the particles in cell lines expressing different levels of folate receptors was studied. Flow cytometry was used to quantify the mean number of nanoparticles internalized per cell. Five times more particles were internalized by cancer cells expressing folate receptors as compared to the normal cells expressing low levels of the receptor. Not only the number of nanoparticles internalized per cell, but also the fraction of cells that had internalized nanoparticles was higher. The total number of particles internalized by the cancer cells was, therefore, about an order of magnitude higher than the total number of particles internalized by normal cells, a difference high enough to be of significant biological importance. In addition, the biospecifically tagged hybrid PEI-silica particles were shown to be noncytotoxic and able to specifically target folate receptor-expressing cancer cells also under coculture conditions.

A series of mesoscopically ordered silicas with different pore sizes, pore connectivity, and pore geometry have been studied as carrier matrices for controlled drug delivery systems. Ibuprofen was used as a model drug, and the release processes were monitored under in vitro conditions. The adsorption of ibuprofen from hexane was shown to be of Langmuir type in all cases, and the degree of drug loading was dependent on the specific surface area and the pore diameter of the host matrix. The release process is found to be mainly diffusion controlled, but clear differences were observed between the studied materials, which we mainly ascribe to differences in the pore connectivity and pore geometry of the materials, and the aqueous stability of the matrix. The studied nanostructured silicas display a high degree of drug loading, and, depending on the host material, a controlled drug release can be provided for time periods varying from hours to weeks.

One of the big challenges of medicine today is to deliver drugs specifically to defected cells. Nanoparticulate drug carriers have the potential to answer to this call, as nanoparticles can cross physiological barriers and access different tissues, and also be provided in a targetable form aimed at enhancing cell specificity of the carrier. Recent developments within material science and strong collaborative efforts crossing disciplinary borders have highlighted the potential of mesoporous silica nanoparticles (MSNs) for such targeted drug delivery. Here we outline recent advances which in this sense push MSNs to the forefront of drug delivery development. Relatively straightforward inside-out tuning of the vehicles, high flexibility, and potential for sophisticated release mechanisms make these nanostructures promising candidates for targeted drug delivery such as 'smart' cancer therapies. Moreover, due to the large surface area and the controllable surface functionality of MSNs, they can be controllably loaded with large amounts of drugs and coupled to homing molecules to facilitate active targeting, simultaneously carrying traceable (fluorescent or magnetically active) modalities, also making them highly interesting as theragnostic agents. However, the increased relative surface area and small size, and flexible surface functionalization which is beneficially exploited in nanomedicine, consequently also includes potential risks in their interactions with biological systems. Therefore, we also discuss some safety issues regarding MSNs and highlight how different features of the drug delivery platform influence their behaviour in a biological setting. Addressing these burning questions will facilitate the application of MSNs in nanomedicine.

Solid lipid nanoparticles (SLNs) are nanocarriers developed as substitute colloidal drug delivery systems parallel to liposomes, lipid emulsions, polymeric nanoparticles, and so forth. Owing to their unique size dependent properties and ability to incorporate drugs, SLNs present an opportunity to build up new therapeutic prototypes for drug delivery and targeting. SLNs hold great potential for attaining the goal of targeted and controlled drug delivery, which currently draws the interest of researchers worldwide. The present review sheds light on different aspects of SLNs including fabrication and characterization techniques, formulation variables, routes of administration, surface modifications, toxicity, and biomedical applications.

Nanotechnology may help overcome persisting limitations of current cancer treatment and thus contribute to the creation of more effective, safer and more affordable therapies. While some nanotechnology-based drug delivery systems are already being marketed and others are in clinical trial, most still remain in the preclinical development stage. Mesoporous silica nanoparticles have been highlighted as an interesting drug delivery platform, due to their flexibility and high drug load potential. Although numerous reports demonstrate sophisticated drug delivery mechanisms in vitro, the therapeutic benefit of these systems for in vivo applications have been under continuous debate. This has been due to nontranslatable conditions used in the in vitro studies, as well as contradictory conclusions drawn from preclinical (in vivo) studies. However, recent studies have indicated that the encouraging cellular studies could in fact be repeated also in vivo. Here, we report on these recent advances regarding therapeutic efficacy, targeting and safety issues related to the application of mesoporous silica nanoparticles in cancer therapy.

Surface functionalization is one of the key steps toward the utilization of mesoporous materials in different applications. In this study, we characterized amino-functionalized mesoporous SBA-15 silicas that have been prepared by different means; co-condensation, post-grafting of amino-silanes, and surface hyperbranching polymerization of poly(ethylene imine). Special focus is put on the accessibility of the introduced function. The materials are thoroughly characterized both by structural and by surface chemical means. We generally observe a good agreement between the C-value derived from BET surface area analysis, the number of accessible amine groups determined by quantitative imine reaction in solution, and zeta-potential measurements. Furthermore, indirect information about differences in the number of amine groups present on the outside surface of the particles can also be obtained. Our results clearly show that there are large differences between the availability of the amine function for materials functionalized by different methods and that the differences calculated as the number of accessible amine groups per unit area can be as large as 20-fold. The co-condensation route is the least efficient surface functionalization method under the studied conditions, and we actually observed a decrease not only in the relative but also the absolute number of accessible amine groups per unit area with an increasing amino-silane molar fraction for the co-condensed materials, which indicates that the commonly used gravimetrical means for determining the extent of true surface functionalization may give rise to large errors. Surface polymerization leads to the highest number of accessible amine groups, but often, the first polymerization cycle leads to polymer formation in micropores in the mesopore walls, which renders these amine groups inaccessible. These results demonstrate that the real surface composition of surfacefunctionalized mesoporous materials may have very little in common with the schematic representations often found in the literature.

Targeted nanoparticle-mediated intracellular delivery is demonstrated using two hydrophobic fluorophores as model drug cargo. The presented hybrid carrier system exhibits both cancer cell-targeting ability and capacity to retain a hydrophobic agent with subsequent specific release into the endosomal compartment. Furthermore, the incorporated agent is shown to be able to escape from the endosomes into the cytoplasm, making the particles promising candidates as carriers for targeted drug delivery for cancer treatment.

Notch signaling, a key regulator of stem cells, is frequently overactivated in cancer. It is often linked to aggressive forms of cancer, evading standard treatment highlighting Notch as an exciting therapeutic target. Notch is in principle "druggable" by γ-secretase inhibitors (GSIs), inhibitory peptides and antibodies, but clinical use of Notch inhibitors is restricted by severe side effects and there is a demand for alternative cancer-targeted therapy. Here, we present a novel approach, using imagable mesoporous silica nanoparticles (MSNPs) as vehicles for targeted delivery of GSIs to block Notch signaling. Drug-loaded particles conjugated to targeting ligands induced cell-specific inhibition of Notch activity in vitro and exhibited enhanced tumor retainment with significantly improved Notch inhibition and therapeutic outcome in vivo. Oral administration of GSI-MSNPs controlled Notch activity in intestinal stem cells further supporting the in vivo applicability of MSNPs for GSI delivery. MSNPs showed tumor accumulation and targeting after systemic administration. MSNPs were biocompatible, and particles not retained within the tumors, were degraded and eliminated mainly by renal excretion. The data highlights MSNPs as an attractive platform for targeted drug delivery of anticancer drugs with otherwise restricted clinical application, and as interesting constituents in the quest for more refined Notch therapies.