The mode of dexamethasone decoration influences avidin-nucleic-acid-nano-assembly organ biodistribution and in vivo drug persistence.

Avidin-Nucleic-Acid-NanoASsemblies (ANANAS) possess natural tropism for the liver and, when loaded with dexamethasone, reduce clinical progression in an autoimmune hepatitis murine model. Here, we investigated the linker chemistry (hydrazide-hydrazone, Hz-Hz, or carbamate hydrazide-hydrazone, Cb-Hz bond) and length (long, 5 kDa PEG, or short, 5-6 carbons) in biotin-dexamethasone conjugates used for nanoparticle decoration through in vitro and in vivo studies. All four newly synthesized conjugates released the drug at acidic pH only. In vitro, the Hz-Hz and the PEG derivatives were less stable than the Cb-Hz and the short chain ones, respectively. Once injected in healthy mice, dexamethasone location in the PEGylated ANANAS outer layer favors liver penetration and resident macrophages uptake, while drug Hz-Hz, but not Cb-Hz, short spacing prolongs drug availability. In conclusion, the tight modulation of ANANAS decoration can significantly influence the host interaction, paving the way for the development of steroid nanoformulations suitable for different pharmacokinetic profiles.

Angiotensin II Promotes SARS-CoV-2 Infection via Upregulation of ACE2 in Human Bronchial Cells.

Blockers of the renin-angiotensin system (RAS) have been reported to increase the angiotensin converting enzyme (ACE)2, the cellular receptor of SARS-CoV-2, and thus the risk and course of COVID-19. Therefore, we investigated if angiotensin (Ang) II and RAS blockers affected ACE2 expression and SARS-CoV-2 infectivity in human epithelial bronchial Calu-3 cells. By infectivity and spike-mediated cell-cell fusion assays, we showed that Ang II acting on the angiotensin type 1 receptor markedly increased ACE2 at mRNA and protein levels, resulting in enhanced SARS-CoV-2 cell entry. These effects were abolished by irbesartan and not affected by the blockade of ACE-1-mediated Ang II formation with ramipril, and of ACE2- mediated Ang II conversion into Ang 1-7 with MLN-4760. Thus, enhanced Ang II production in patients with an activated RAS might expose to a greater spread of COVID-19 infection in lung cells. The protective action of Angiotensin type 1 receptor antagonists (ARBs) documented in these studies provides a mechanistic explanation for the lack of worse outcomes in high-risk COVID-19 patients on RAS blockers.

The p.R1819_C1948delinsS mutation makes von Willebrand factor ADAMTS13-resistant and reduces its collagen-binding capacity.

This report concerns abnormal ADAMTS13 (a disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13) and collagen interactions coinciding with the p.R1819_C1948delinsS von Willebrand factor (VWF) mutation associated with the deletion of the C-terminus of the A3 domain (amino acids 1819-1947) in a patient with a history of bleeding. The von Willebrand disease (VWD) phenotype of the patient featured low plasma and platelet VWF, multimers with smears extending over the highest normal oligomers in plasma, but not platelets, and an impaired collagen-binding capacity. In vitro full-length p.R1819_C1948delinsS VWF expression showed impaired VWF release, increased cellular content with normally-multimerized VWF and impaired collagen binding. The recombinant p.R1819_C1948delinsS VWF fragment, extending from domains A2 to B3 (p.R1819_C1948delinsS A2-B3 VWF), was completely resistant to proteolysis by ADAMTS13 in the presence of 1·5 mol/l urea, unlike its normal counterpart. The defect stems from impaired ADAMTS13 binding to p.R1819_C1948delinsS A2-B3, analysed under static conditions. Partial deletion of the C-terminus of the A3 domain thus makes VWF resistant to ADAMTS13, interfering with ADAMTS13 binding to VWF, and impairing the collagen-binding capacity of VWF. The p.R1819_C1948delinsS mutation has both haemorrhagic features (defective collagen binding, reduced VWF levels) and prothrombotic (ADAMTS13 resistance) features, and the latter probably mitigate the patient's bleeding symptoms.

Higher and lower active circulating VWF levels: different facets of von Willebrand disease.

Most circulating von Willebrand factor (VWF) is normally inactive and incapable of binding platelets, but numerous disorders may modify the proportion of active VWF. We explored active VWF levels in patients with von Willebrand disease (VWD) whose VWF had a higher affinity for platelet glycoprotein (GP)Ib, but different susceptibilities to ADAMTS13 and multimer patterns (9 patients lacking large multimers, 10 with a normal pattern); 12 patients with VWF C2362F and R1819_C1948delinsS mutations, which make VWF resistant to ADAMTS13 were also studied. Type 2B patients with abnormal or normal multimers had significantly more active VWF (3·33 ± 1·6 and 3·74 ± 0·74, respectively; normal 0·99 ± 0·23). The type of VWF mutation influenced VWF activation: V1316M was associated with the highest levels in patients with abnormal multimers, and R1341W in those with normal multimers. Pregnancy induced gradually rising active VWF levels and declining platelet counts in one type 2B VWD patient without large multimers. Active VWF levels dropped significantly in patients homozygous for the C2362F mutation or heterozygous for R1819_C1948delinsS mutations (0·2 ± 0·03 and 0·23 ± 0·1, respectively), and less in cases heterozygous for the VWF C2362F mutation (0·55 ± 0·17). We demonstrate that VWF may be more or less activated, with or without any direct involvement of the A1 domain, and regardless of ADAMTS13.

RAndomized Clinical Trial Of NAfamostat Mesylate, A Potent Transmembrane Protease Serine 2 (TMPRSS2) Inhibitor, in Patients with COVID-19 Pneumonia.

Even though SARS-CoV-2 was declared by WHO as constituting no longer a public health emergency, the development of effective treatments against SARS-CoV-2 infection remains a critical issue to prevent complications, particularly in fragile patients. The protease inhibitor nafamostat, currently used in Japan and Korea for pancreatitis, owing to its anticoagulant properties for disseminated intravascular coagulation (DIC), is appealing for the treatment of COVID-19 infection, because it potently inhibits the transmembrane protease serine 2 (TMPRSS2) that, after virus binding to ACE-2, allows virus entry into the cells and replication. Moreover, it could prevent the DIC and pulmonary embolism frequently associated with COVID-19 infection. The goal of the RAndomized Clinical Trial Of NAfamostat (RACONA) study, designed as a prospective randomized, double-blind placebo-controlled clinical trial, was to investigate the efficacy and safety of nafamostat mesylate (0.10 mg/kg/h iv for 7 days), on top of the optimal treatment, in COVID-19 hospitalized patients. We could screen 131 patients, but due to the predefined strict inclusion and exclusion criteria, only 15 could be randomized to group 1 (n = 7) or group 2 (n = 8). The results of an ad interim safety analysis showed similar overall trends for variables evaluating renal function, coagulation, and inflammation. No adverse events, including hyperkalemia, were found to be associated with nafamostat. Thus, the RACONA study showed a good safety profile of nafamostat, suggesting that it could be usefully used in COVID-19 hospitalized patients.

Efficient SARS-CoV-2 infection antagonization by rhACE2 ectodomain multimerized onto the Avidin-Nucleic-Acid-NanoASsembly.

Nanodecoy systems based on analogues of viral cellular receptors assembled onto fluid lipid-based membranes of nano/extravescicles are potential new tools to complement classic therapeutic or preventive antiviral approaches. The need for lipid-based membranes for transmembrane receptor anchorage may pose technical challenges along industrial translation, calling for alternative geometries for receptor multimerization. Here we developed a semisynthetic self-assembling SARS-CoV-2 nanodecoy by multimerizing the biotin labelled virus cell receptor -ACE2- ectodomain onto a poly-avidin nanoparticle (NP) based on the Avidin-Nucleic-Acid-NanoASsembly-ANANAS. The ability of the assembly to prevent SARS-CoV-2 infection in human lung cells and the affinity of the ACE2:viral receptor-binding domain (RBD) interaction were measured at different ACE2:NP ratios. At ACE2:NP = 30, 90 % SARS-CoV-2 infection inhibition at ACE2 nanomolar concentration was registered on both Wuhan and Omicron variants, with ten-fold higher potency than the monomeric protein. Lower and higher ACE2 densities were less efficient suggesting that functional recognition between multi-ligand NPs and multi-receptor virus surfaces requires optimal geometrical relationships. In vivo studies in mice showed that the biodistribution and safety profiles of the nanodecoy are potentially suitable for preventing viral infection upon nasal instillation. Viral receptor multimerization using ANANAS is a convenient process which, in principle, could be rapidly adapted to counteract also other viral infections.

Characterization of multifunctional nanosystems based on the avidin-nucleic acid interaction as signal enhancers in immuno-detection.

The Avidin-Nucleic-Acids-Nano-Assembly (ANANAS) is a kind of soft poly avidin nanoparticle originating from the high affinity interaction between avidin and the nucleic acids. In this work we investigated the possibility of transforming ANANAS cores into stoichiometrically controlled multifunctional nanoparticles through a "one-pot" procedure, and we measured in a quantitative way their ability to work as reagents for enhanced immunodiagnostic detection. Initially, we measured the ANANAS loading capability for biotinylated proteins of different nature. About 200 molecules of biotin-horseradish-peroxidase (40KDa b-HRP) and 60 molecules of biotin-immunoglobulin-G (150KDa b-IgG) could be accommodated onto each nanoparticle, showing that steric limitations dictate the number of loadable entities. Stoichiometrically controlled functional assemblies were generated by mixing core particles with subsaturating amounts of b-HRP and b-IgG. When applied as detection reagents in an Enzyme-Linked-ImmunoSorbed-Assay (ELISA), these assemblies were up to two-orders of magnitude more sensitive than commercial HRP-based reagents. Assemblies of different composition displayed different efficacy, indicating that the system functionality can be fine-tuned. Within-assay variability (CV%), measured to assess if the assembly procedure is reproducible, was within 10%. Stability experiments demonstrated that the functionalyzed assemblies are stable in solution for more than one week. In principle, any biotinylated function can be loaded onto the core particle, whose high loading capacity and tunability may open the way toward further application in biomedicine.

Synthesis and chromatography-free purification of PNA-PEO conjugates for the functionalisation of gold sensors.

Peptide Nucleic Acids (PNAs) linked to high molecular weight (MW) poly(ethylene oxide) (PEO) derivatives could be useful conjugates for the direct functionalisation of gold surfaces dedicated to Surface Plasmon Resonance (SPR)-based DNA sensing. However their use is hampered by the difficulty to obtain them through a convenient and economical route. In this work we compared three synthetic strategies to obtain PNA-high MW PEO conjugates composed of (a) a 15-mer PNA sequence as the probe complementary to genomic DNA of ]Mycobacterium tuberculosis, (b) a PEO moiety (2 or 5 KDa MW) and (c) a terminal trityl-protected thiol necessary (after acidic deprotection) for grafting to gold surfaces. The 15-mer PNA was obtained by solid-phase synthesis. Its amino terminal group was later condensed to bi-functional PEO derivatives (2 and 5 KDa MW) carrying a Trt-cysteine at one end and a carboxyl group at the other end. The reaction was carried out either in solution, using HATU or PyOxim as coupling agents, or through the solid-phase approach, with 49.6%, 100% and 5.2% yield, respectively. A differential solvent extraction strategy for product purification without the need for chromatography is described. The ability of the 5 KDa PEO conjugate to function as a probe for complementary DNA detection was demonstrated using a Grating-Coupling Surface Plasmon Resonance (GC-SPR) system. The optimized PEO conjugation and purification protocols are economical and simple enough to be reproduced also within laboratories that are not highly equipped for chemical synthesis.

Semisolid Wet Sol-Gel Silica/Hydroxypropyl Methyl Cellulose Formulation for Slow Release of Serpin B3 Promotes Wound Healing In Vivo.

Foot ulcerations are a disabling complication of diabetes and no treatment is currently available based on disease mechanisms. The protein serpin B3 (SB3) was identified as a positive biomarker of successful diabetic wound healing; therefore, its exogenous administration may promote healing. The topical administration of SB3 is challenging due to its protein nature. Physical entrapment in wet sol-gel silica can stabilize the protein's conformation and permit its sustained delivery. However, irreversible syneresis and poor viscoelastic properties hamper wet sol-gel silica application as a semisolid vehicle. To overcome these limits, a sol-gel silica/hydroxypropylmethylcellulose (HPMC) hydrogel blend was developed. SB3 entrapped in 8% SiO2 wet sol-gel silica preserved its structure, was stabilized against denaturation, and was slowly released for at least three days. Blending a silica gel with an HPMC-glycerol (metolose-G) hydrogel permitted spreadability without affecting the protein's release kinetics. When administered in vivo, SB3 in silica/metolose-G-but not in solution or in metolose-G alone-accelerated wound healing in SB3 knockout and diabetic mouse models. The results confirmed that SB3 is a new pharmacological option for the treatment of chronic ulcers, especially when formulated in a slow-releasing vehicle. Silica-metolose-G represents a novel type of semisolid dosage form which could also be applied for the formulation of other bioactive proteins.

Development of a Nanoparticle-Based Approach for the Blood-Brain Barrier Passage in a Murine Model of Amyotrophic Lateral Sclerosis.

The development of nanoparticles (NPs) to enable the passage of drugs across blood-brain barrier (BBB) represents one of the main challenges in neuropharmacology. In recent years, NPs that are able to transport drugs and interact with brain endothelial cells have been tested. Here, we investigated whether the functionalization of avidin-nucleic-acid-nanoassembly (ANANAS) with apolipoprotein E (ApoE) would allow BBB passage in the SOD1G93A mouse model of amyotrophic lateral sclerosis. Our results demonstrated that ANANAS was able to transiently cross BBB to reach the central nervous system (CNS), and ApoE did not enhance this property. Next, we investigated if ANANAS could improve CNS drug delivery. To this aim, the steroid dexamethasone was covalently linked to ANANAS through an acid-reversible hydrazone bond. Our data showed that the steroid levels in CNS tissues of SOD1G93A mice treated with nanoformulation were below the detection limit. This result demonstrates that the passage of BBB is not sufficient to guarantee the release of the cargo in CNS and that a different strategy for drug tethering should be devised. The present study furthermore highlights that NPs can be useful in improving the passage through biological barriers but may limit the interaction of the therapeutic compound with the specific target.

Optimized avidin nucleic acid nanoassemblies by a tailored PEGylation strategy and their application as molecular amplifiers in detection.

Avidin was recently found to display the ability to interact with high affinity with nucleic acids. In this work, we investigated how this property is affected by the protein modification with poly(ethylene glycol) (PEG). More precisely, we studied the influence of the size and geometry of the polymer and of the mode of anchorage to the protein surface. To this end, we synthesized five PEG derivatives capable of PEGylating avidin either through covalent attachment to its lysine primary amines or by exploiting its biotin binding pockets. Several differently PEGylated avidin derivatives were then obtained, which were later tested for their affinity for plasmid DNA by means of the electrophoretic mobility assay. The results show that covalent PEGylation reduces the affinity for DNA in a dose-dependent manner, whereas PEG anchoring through the biotin binding sites does not, even when bulky and high MW biotin-PEG derivatives are used. We then investigated how the size and molecular weight of the biotin-PEG affects the solubility and stability of avidin-nucleic acid nanoassemblies in physiological buffer. Among the biotin-PEG derivatives synthesized in this work, the branched forms were more efficient in protecting particle surface and preventing their aggregation. Full nanoparticle solubility was achieved by saturating 30% of the biotin binding sites with a 2 x 5 kDa branched derivative. the optimized avidin nucleic acid nanoassemblies (ANANAS) were employed in a model analytical test where they showed at least 40-fold higher efficiency than monomeric avidin in recognizing biotinylated surface immobilized IgGs. The results pave the way toward the application of this novel nanosystem in biomedicine.

Dexamethasone Conjugation to Biodegradable Avidin-Nucleic-Acid-Nano-Assemblies Promotes Selective Liver Targeting and Improves Therapeutic Efficacy in an Autoimmune Hepatitis Murine Model.

Steroids are the standard therapy for autoimmune hepatitis (AIH) but the long-lasting administration is hampered by severe side effects. Methods to improve the tropism of the drug toward the liver are therefore required. Among them, conjugation to nanoparticles represents one possible strategy. In this study, we exploited the natural liver tropism of Avidin-Nucleic-Acid-Nano-Assemblies (ANANAS) to carry dexamethasone selectively to the liver in an AIH animal model. An acid-labile biotin-hydrazone linker was developed for reversible dexamethasone loading onto ANANAS. The biodistribution, pharmacokinetics and efficacy of free and ANANAS-linked dexamethasone (ANANAS-Hz-Dex) in healthy and AIH mice were investigated upon intraperitoneal administration. In ANANAS-treated animals, the free drug was detected only in the liver. Super-resolution microscopy showed that nanoparticles segregate inside lysosomes of liver immunocompetent cells, mainly involved in AIH progression. In agreement with these observational results, chronic low-dose treatment with ANANAS-Hz-Dex reduced the expression of liver inflammation markers and, in contrast to the free drug, also the levels of circulating AIH-specific autoantibodies. These data suggest that the ANANAS carrier attenuates AIH-related liver damage without drug accumulation in off-site tissues. The safety and biodegradability of the ANANAS carrier make this formulation a promising tool for the treatment of autoimmune liver disorders.

Improvement and extension of anti-EGFR targeting in breast cancer therapy by integration with the Avidin-Nucleic-Acid-Nano-Assemblies.

Nowadays, personalized cancer therapy relies on small molecules, monoclonal antibodies, or antibody-drug conjugates (ADC). Many nanoparticle (NP)-based drug delivery systems are also actively investigated, but their advantage over ADCs has not been demonstrated yet. Here, using the Avidin-Nucleic-Acid-Nano-Assemblies (ANANAS), a class of polyavidins multifuctionalizable with stoichiometric control, we compare quantitatively anti-EGFR antibody(cetuximab)-targeted NPs to the corresponding ADC. We show that ANANAS tethering of cetuximab promotes a more efficient EGFR-dependent vesicle-mediated internalization. Cetuximab-guided ANANAS carrying doxorubicin are more cytotoxic in vitro and much more potent in vivo than the corresponding ADC, leading to 43% tumor reduction at low drug dosage (0.56 mg/kg). Advantage of cetuximab-guided ANANAS with respect to the ADC goes beyond the increase in drug-to-antibody ratio. Even if further studies are needed, we propose that NP tethering could expand application of the anti-EGFR antibody to a wider number of cancer patients including the KRAS-mutated ones, currently suffering from poor prognosis.

A single-step photolithographic interface for cell-free gene expression and active biochips.

We have developed a biochip platform technology suitable for controlled cell-free gene expression at the micrometer scale. A new hybrid molecule, "Daisy", was designed and synthesized to form in a single step a biocompatible lithographic interface on silicon dioxide. A protocol is described for the immobilization of linear DNA molecules thousands of base pairs long on Daisy-coated surfaces with submicrometer spatial resolution and up to high densities. On-chip protein synthesis can be obtained with a dynamic range of up to four orders of magnitude and minimal nonspecific activity. En route to on-chip artificial gene circuits, a simple two-stage gene cascade was built, in which the protein synthesized at the first location diffuses to regulate the synthesis of another protein at a second location. We demonstrate the capture of proteins from crude extract onto micrometer-scale designated traps, an important step for the formation of miniaturized self-assembled protein chips. Our biochip platform can be combined with elastomeric microfluidic devices, thereby opening possibilities for isolated and confined reaction chambers and artificial cells in which the transport of products and reagents is done by diffusion and flow. The Daisy molecule and described approach enables groups not proficient in surface chemistry to construct active biochips based on cell-free gene expression.

Gold-silver alloy semi-nanoshell arrays for label-free plasmonic biosensors.

Nanosphere lithography coupled with reactive ion etching has been used to synthesize hexagonal ordered arrays of Au-Ag bimetallic semi-nanoshells to be used as plasmonic biosensors. The degree of lateral interaction between adjacent semi-nanoshells can be controlled by tailoring the reactive ion etching time in order to boost the global plasmonic properties through the formation of near-field hot-spots, which in turn can improve the sensitivity of the biosensors. To test the efficiency of the proposed system as a biosensor, we used an established protocol for the detection of biomolecules (local sensitivity), based on the receptor-ligand approach and using the biotin-streptavidin model system. We also tested the sensitivity to a homogeneous change in the refractive index of the buffer over the sensor (bulk sensitivity). Comparing the obtained results to those of an array of nanoprisms, chosen as a benchmark, significantly higher performances both in local and bulk sensitivities have been found, in agreement with electrodynamics simulations based on finite-element methods.

Evaluation of silicon dioxide-based coating enriched with bioactive peptides mapped on human vitronectin and fibronectin: in vitro and in vivo assays.

A wide range of biochemical signals promoting cell functions (adhesion, migration, proliferation, and differentiation) and thereby improving the osseointegration process are currently investigated. Unfortunately, their application for the production of bioactive implantable devices is often hampered by their insolubility; instability; and limited availability of a large amount of inexpensive, high-purity samples. An attractive alternative is the use of short peptides carrying the minimum active sequence of the natural factors. Synthetic peptides mapped on fibronectin and vitronectin have been demonstrated to enhance cell adhesion both to polystyrene and acellular bone matrix; in particular, a nonapeptide sequence from human vitronectin works via an osteoblast-specific adhesion mechanism. In this study, we incorporated these peptides into a sol-gel silica dressing applied to coat sand-blasted and acid-attacked titanium samples; measured the kinetic of peptide release; and used titanium disks, coated with a peptide-enriched film, as substrates to determine the peptide concentration that maximizes cell adhesion in vitro. We also evaluated in vivo the capacity of the vitronectin-derived peptide to improve osteogenic activity: histologic analysis revealed markedly improved osteogenic activity around peptide-enriched samples. This article also discusses the role of surface characteristics and the importance of bioactive peptides.

Wet sol-gel derived silica for controlled release of proteins.

The potential of wet sol-gel derived silica gels as new matrices for the entrapment and sustained release of proteins was investigated. Model proteins, BSA, ribonuclease-A and avidin, with differing molecular weights and/or isoelectric points, were entrapped in two silica polymer formulations having different silica contents (4% and 12% wt/v). The conformational stability of the proteins after entrapment and their release after immersion into physiological conditions were measured. Circular dichroism analysis showed that protein conformation is maintained after entrapment and stability is enhanced. Protein-free formulations were injected intramuscularly into BALB/c mice to monitor the in vivo fate of the matrix, and the results showed that the gel is totally reabsorbed, without any apparent surrounding inflammation process. The time required for matrix bioerosion varied between one to three weeks, depending on its SiO(2) content. Erosion was also measured in vitro and the contribution of erosion and diffusion to the release of the embedded proteins was quantified. These data indicate that wet silica polymers obtained by the sol-gel route are promising matrices for the sustained release of protein drugs.

A New ELISA Using the ANANAS Technology Showing High Sensitivity to diagnose the Bovine Rhinotracheitis from Individual Sera to Pooled Milk.

Diagnostic tests for veterinary surveillance programs should be efficient, easy to use and, possibly, economical. In this context, classic Enzyme linked ImmunoSorbent Assay (ELISA) remains the most common analytical platform employed for serological analyses. The analysis of pooled samples instead of individual ones is a common procedure that permits to certify, with one single test, entire herds as "disease-free". However, diagnostic tests for pooled samples need to be particularly sensitive, especially when the levels of disease markers are low, as in the case of anti-BoHV1 antibodies in milk as markers of Infectious Bovine Rhinotracheitis (IBR) disease. The avidin-nucleic-acid-nanoassembly (ANANAS) is a novel kind of signal amplification platform for immunodiagnostics based on colloidal poly-avidin nanoparticles that, using model analytes, was shown to strongly increase ELISA test performance as compared to monomeric avidin. Here, for the first time, we applied the ANANAS reagent integration in a real diagnostic context. The monoclonal 1G10 anti-bovine IgG1 antibody was biotinylated and integrated with the ANANAS reagents for indirect IBR diagnosis from pooled milk mimicking tank samples from herds with IBR prevalence between 1 to 8%. The sensitivity and specificity of the ANANAS integrated method was compared to that of a classic test based on the same 1G10 antibody directly linked to horseradish peroxidase, and a commercial IDEXX kit recently introduced in the market. ANANAS integration increased by 5-fold the sensitivity of the 1G10 mAb-based conventional ELISA without loosing specificity. When compared to the commercial kit, the 1G10-ANANAS integrated method was capable to detect the presence of anti-BHV1 antibodies from bulk milk of gE antibody positive animals with 2-fold higher sensitivity and similar specificity. The results demonstrate the potentials of this new amplification technology, which permits improving current classic ELISA sensitivity limits without the need for new hardware investments.

Mesoporous silica sub-micron spheres as drug dissolution enhancers: Influence of drug and matrix chemistry on functionality and stability.

Mesoporous silica particles prepared through a simplified Stöber method and low temperature solvent promoted surfactant removal are evaluated as dissolution enhancers for poorly soluble compounds, using a powerful anticancer agent belonging to pyrroloquinolinones as a model for anticancer oral therapy, and anti-inflammatory ibuprofen as a reference compound. Mesoporous powders composed of either pure silica or silica modified with aminopropyl residues are produced. The influence of material composition and drug chemical properties on drug loading capability and dissolution enhancement are studied. The two types of particles display similar size, surface area, porosity, erodibility, drug loading capability and stability. An up to 50% w/w drug loading is reached, showing correlation between drug concentration in adsorption medium and content in the final powder. Upon immersion in simulating body fluids, immediate drug dissolution occurred, allowing acceptor solutions to reach concentrations equal to or greater than drug saturation limits. The matrix composition influenced drug solution maximal concentration, complementing the dissolution enhancement generated by a mesoporous structure. This effect was found to depend on both matrix and drug chemical properties allowing us to hypothesise general prediction behaviour rules.