Multifunctional Biomimetic Nanovaccines Based on Photothermal and Weak-Immunostimulatory Nanoparticulate Cores for the Immunotherapy of Solid Tumors.

An alternative strategy of choosing photothermal and weak-immunostimulatory porous silicon@Au nanocomposites as particulate cores to prepare a biomimetic nanovaccine is reported to improve its biosafety and immunotherapeutic efficacy for solid tumors. A quantitative analysis method is used to calculate the loading amount of cancer cell membranes onto porous silicon@Au nanocomposites. Assisted with foreign-body responses, these exogenous nanoparticulate cores with weak immunostimulatory effect can still efficiently deliver cancer cell membranes into dendritic cells to activate them and the downstream antitumor immunity, resulting in no occurrence of solid tumors and the survival of all immunized mice during 55 day observation.

Biohybrid Vaccines for Improved Treatment of Aggressive Melanoma with Checkpoint Inhibitor.

Recent approaches in the treatment of cancer focus on involving the immune system to control the tumor growth. The administration of immunotherapies, like checkpoint inhibitors, has shown impressive results in the long term survival of patients. Cancer vaccines are being investigated as further tools to prime tumor-specific immunity.

Pretargeted PET Imaging of -Cyclooctene-Modified Porous Silicon Nanoparticles.

Pretargeted positron emission tomography (PET) imaging based on bioorthogonal chemical reactions has proven its potential in immunoimaging. It may also have great potential in nanotheranostic applications. Here, we report the first successful pretargeted PET imaging of -cyclooctene-modified mesoporous silicon nanoparticles, using F-labeled tetrazine as a tracer.

Coating Nanoparticles with Plant-Produced Transferrin-Hydrophobin Fusion Protein Enhances Their Uptake in Cancer Cells.

The encapsulation of drugs to nanoparticles may offer a solution for targeted delivery. Here, we set out to engineer a self-assembling targeting ligand by combining the functional properties of human transferrin and fungal hydrophobins in a single fusion protein. We showed that human transferrin can be expressed in Nicotiana benthamiana plants as a fusion with Trichoderma reesei hydrophobins HFBI, HFBII, or HFBIV.

Delivery of Flightless I siRNA from Porous Silicon Nanoparticles Improves Wound Healing in Mice.

Flightless I (Flii), a cytoskeletal actin remodelling protein, is elevated in wounds and is a negative regulator of wound healing. Gene silencing using small interfering RNA (siRNA) is an attractive approach to antagonize Flii, and therefore holds significant promise as a therapeutic intervention. The development of siRNA therapeutics has been limited by an inability of the siRNA to cross the cell surface plasma membrane of target cells and also by their degradation due to endogenous nuclease action.

Active diffusion of nanoparticles of maternal origin within the embryonic brain.

Aim: To investigate porous silicon (PSi) nanoparticles (NPs) behavior in the embryonic brain.

Materials & Methods: Fluorescently labeled PSi NPs were injected into the embryonic brains intraventricularly and to the mother intravenously (iv.).

In vitro and in vivo assessment of heart-homing porous silicon nanoparticles.

Chronic heart failure, predominantly developed after myocardial infarction, is a leading cause of high mortality worldwide. As existing therapies have still limited success, natural and/or synthetic nanomaterials are emerging alternatives for the therapy of heart diseases. Therefore, we aimed to functionalize undecylenic acid thermally hydrocarbonized porous silicon nanoparticles (NPs) with different targeting peptides to improve the NP's accumulation in different cardiac cells (primary cardiomyocytes, non-myocytes, and H9c2 cardiomyoblasts), additionally to investigate the behavior of the heart-targeted NPs in vivo.

Microfluidic Assembly of a Multifunctional Tailorable Composite System Designed for Site Specific Combined Oral Delivery of Peptide Drugs.

Multifunctional tailorable composite systems, specifically designed for oral dual-delivery of a peptide (glucagon-like peptide-1) and an enzymatic inhibitor (dipeptidyl peptidase 4 (DPP4)), were assembled through the microfluidics technique. Both drugs were coloaded into these systems for a synergistic therapeutic effect. The systems were composed of chitosan and cell-penetrating peptide modified poly(lactide-co-glycolide) and porous silicon nanoparticles as nanomatrices, further encapsulated in an enteric hydroxypropylmethylcellulose acetylsuccinate polymer.

Multifunctional porous silicon nanoparticles for cancer theranostics.

Nanomaterials provide a unique platform for the development of theranostic systems that combine diagnostic imaging modalities with a therapeutic payload in a single probe. In this work, dual-labeled iRGD-modified multifunctional porous silicon nanoparticles (PSi NPs) were prepared from dibenzocyclooctyl (DBCO) modified PSi NPs by strain-promoted azide-alkyne cycloaddition (SPAAC) click chemistry. Hydrophobic antiangiogenic drug, sorafenib, was loaded into the modified PSi NPs to enhance the drug dissolution rate and improve cancer therapy.

Dual-drug delivery by porous silicon nanoparticles for improved cellular uptake, sustained release, and combination therapy.

Dual-drug delivery of antiangiogenic and chemotherapeutic drugs can enhance the therapeutic effect for cancer therapy. Conjugation of methotrexate (MTX) to porous silicon (PSi) nanoparticles (MTX-PSi) with positively charged surface can improve the cellular uptake of MTX and inhibit the proliferation of cancer cells. Herein, MTX-PSi conjugates sustained the release of MTX up to 96 h, and the released fragments including MTX were confirmed by mass spectrometry.

Functionalization of alkyne-terminated thermally hydrocarbonized porous silicon nanoparticles with targeting peptides and antifouling polymers: effect on the human plasma protein adsorption.

Porous silicon (PSi) nanomaterials combine a high drug loading capacity and tunable surface chemistry with various surface modifications to meet the requirements for biomedical applications. In this work, alkyne-terminated thermally hydrocarbonized porous silicon (THCPSi) nanoparticles were fabricated and postmodified using five bioactive molecules (targeting peptides and antifouling polymers) via a single-step click chemistry to modulate the bioactivity of the THCPSi nanoparticles, such as enhancing the cellular uptake and reducing the plasma protein association. The size of the nanoparticles after modification was increased from 176 to 180-220 nm.

Surface chemistry dependent immunostimulative potential of porous silicon nanoplatforms.

Nanoparticles (NPs) have been suggested for immunotherapy applications in order to optimize the delivery of immuno-stimulative or -suppressive molecules. However, low attention towards the impact of the NPs' physicochemical properties has presented a major hurdle for developing efficient immunotherapeutic agents. Here, the effects of porous silicon (PSi) NPs with different surface chemistries were evaluated on human monocyte-derived dendritic cells (MDDCs) and lymphocytes in order to highlight the importance of the NPs selection in immuno-stimulative or -suppressive treatment.

The impact of nanoparticles on the mucosal translocation and transport of GLP-1 across the intestinal epithelium.

Glucagon like peptide-1 (GLP-1) is an incretin hormone that is in the pipeline for type 2 diabetes mellitus (T2DM) therapy. However, oral administration of GLP-1 is hindered by the harsh conditions of the gastrointestinal tract and poor bioavailability. In this study, three nanosystems composed by three different biomaterials (poly(lactide-co-glycolide) polymer (PLGA), Witepsol E85 lipid (solid lipid nanoparticles, SLN) and porous silicon (PSi) were developed and loaded with GLP-1 to study their permeability in vitro.

In vivo biocompatibility of porous silicon biomaterials for drug delivery to the heart.

Myocardial infarction (MI), commonly known as a heart attack, is the irreversible necrosis of heart muscle secondary to prolonged ischemia, which is an increasing problem in terms of morbidity, mortality and healthcare costs worldwide. Along with the idea to develop nanocarriers that efficiently deliver therapeutic agents to target the heart, in this study, we aimed to test the in vivo biocompatibility of different sizes of thermally hydrocarbonized porous silicon (THCPSi) microparticles and thermally oxidized porous silicon (TOPSi) micro and nanoparticles in the heart tissue. Despite the absence or low cytotoxicity, both particle types showed good in vivo biocompatibility, with no influence on hematological parameters and no considerable changes in cardiac function before and after MI.

In vivo evaluation of porous silicon and porous silicon solid lipid nanocomposites for passive targeting and imaging.

The use of nanoparticle carriers for the sustained release of cytotoxic drugs in cancer therapy can result in fewer adverse effects and can thus be of great benefit for the patient. Recently, a novel nanocomposite, prepared by the encapsulation of THCPSi nanoparticles within solid lipids (SLN), was developed and characterized as a promising drug delivery carrier in vitro. The present study describes the in vivo evaluation of unmodified THCPSi nanoparticles and THCPSi-solid lipid nanocomposites (THCPSi-SLNCs) as potential drug delivery carriers for cancer therapy by using (18)F radiolabeling for the detection of the particle biodistribution in mice.

Augmented cellular trafficking and endosomal escape of porous silicon nanoparticles via zwitterionic bilayer polymer surface engineering.

The development of a stable vehicle with low toxicity, high cellular internalization, efficient endosomal escape, and optimal drug release profile is a key bottleneck in nanomedicine. To overcome all these problems, we have developed a successful layer-by-layer method to covalently conjugate polyethyleneimine (PEI) and poly(methyl vinyl ether-co-maleic acid) (PMVE-MA) copolymer on the surface of undecylenic acid functionalized thermally hydrocarbonized porous silicon nanoparticles (UnTHCPSi NPs), forming a bilayer zwitterionic nanocomposite containing free positive charge groups of hyper-branched PEI disguised by the PMVE-MA polymer. The surface smoothness, charge and hydrophilicity of the developed NPs considerably improved the colloidal and plasma stabilities via enhanced suspensibility and charge repulsion.

Chitosan-modified porous silicon microparticles for enhanced permeability of insulin across intestinal cell monolayers.

Porous silicon (PSi) based particulate systems are emerging as an important drug delivery system due to its advantageous properties such as biocompatibility, biodegradability and ability to tailor the particles' physicochemical properties. Here, annealed thermally hydrocarbonized PSi (AnnTHCPSi) and undecylenic acid modified AnnTHCPSi (AnnUnTHCPSi) microparticles were developed as a PSi-based platform for oral delivery of insulin. Chitosan (CS) was used to modify the AnnUnTHCPSi microparticles to enhance the intestinal permeation of insulin.

Copper-free azide-alkyne cycloaddition of targeting peptides to porous silicon nanoparticles for intracellular drug uptake.

Porous silicon (PSi) has been demonstrated as a promising drug delivery vector for poorly water-soluble drugs. Here, a simple and efficient method based on copper-free click chemistry was used to introduce targeting moieties to PSi nanoparticles in order to enhance the intracellular uptake and tumor specific targeting hydrophobic drug delivery. Two RGD derivatives (RGDS and iRGD) with azide-terminated groups were conjugated to bicyclononyne-functionalized PSi nanoparticles via copper-free azide-alkyne cycloaddition.

Diatom silica microparticles for sustained release and permeation enhancement following oral delivery of prednisone and mesalamine.

Diatoms are porous silica-based materials obtained from single cell photosynthetic algae. Despite low cost, easy purification process, environmentally safe properties, and rapidly increasing potentials for medical applications, the cytotoxicity of diatoms and the effect on drug permeation of oral formulations have not been studied so far. Herein, we have evaluated the potential of diatom silica microparticles (DSMs) for the delivery of mesalamine and prednisone, which are two commonly prescribed drugs for gastrointestinal (GI) diseases.

Tumour homing peptide-functionalized porous silicon nanovectors for cancer therapy.

Tumour targeting nanoparticles (NPs) have demonstrated great potential for enhancing anticancer drug delivery to tumour sites and for reducing the side effects of chemotherapy. However, many nanoparticulate delivery systems still lack efficient tumour accumulation. In this work, we present a porous silicon (PSi) nanovector functionalized with a tumour-homing peptide, which targets the mammary-derived growth inhibitor (MDGI) expressing cancer cells both in vitro and in vivo, thereby enhancing the accumulation of the NPs in the tumours.

The mechanisms of surface chemistry effects of mesoporous silicon nanoparticles on immunotoxicity and biocompatibility.

Despite steadily increasing insights on the biocompatibility of PSi nanoparticles (NPs), an extensive biosafety study on the immune and red blood cells (RBCs) is still lacking. Herein, we evaluated the impact of the PSi NPs' surface chemistry on immune cells and human RBCs both in vitro and in vivo. Negatively charged hydrophilic and hydrophobic PSi NPs caused less ATP depletion and genotoxicity than the positively charged amine modified hydrophilic PSi NPs, demonstrating the main role of PSi NPs' surface charge on the immunocompatibility profile.

The mucoadhesive and gastroretentive properties of hydrophobin-coated porous silicon nanoparticle oral drug delivery systems.

Impediments to intestinal absorption, such as poor solubility and instability in the variable conditions of the gastrointestinal (GI) tract plague many of the current drugs restricting their oral bioavailability. Particulate drug delivery systems hold great promise in solving these problems, but their effectiveness might be limited by their often rapid transit through the GI tract. Here we describe a bioadhesive oral drug delivery system based on thermally-hydrocarbonized porous silicon (THCPSi) functionalized with a self-assembled amphiphilic protein coating consisting of a class II hydrophobin (HFBII) from Trichoderma reesei.