The effect of nanoparticles on secreted MPO in serum free media.

<p>A- PS-COOH NPs; B- PS-NH2 NPs; C- PS-OSO3 or TiO₂ NPs, as indicated. The supernatants from activated neutrophils were analysed for MPO activity. The results are reported as % of MPO activity in supernatants without added nanoparticles. The results are a mean of three separate experiments each done in duplicate. (#)p < 0,05 compared to control without NPs.</p

Schematic representation of how MPO (green), particle surface and BSA (blue) concentration interplay to define the activity level of MPO.

<p>(A) When purified MPO interacts with the particle surface its interaction modifies the conformation of the protein, which increase enzyme activity. (B) At medium protein concentration the MPO interaction with the surface is influenced by other proteins and is very active. (C) In high protein concentration media the MPO has less access to the surface and is less active either because of less MPO is bound to the surface or that the conformational change is less favorable in a crowded environment.</p

The combined effect of bovine serum albumin alone and albumin with 60 nm PS-COOH on MPO activity.

<p>MPO was mixed with different concentrations of BSA and thereafter with 60 nm PS-COOH before the MPO activity is measured. The results are reported as % of MPO activity in samples without added BSA or nanoparticles. All activities in presence of NPs with or without added BSA are significantly different from activity without BSA (p<0.05).</p

Characteristics of the used nanoparticles.

<p>Characteristics of the used nanoparticles.</p

Interactions between 60 nm PS-COOH NPs and MPO evaluated by SDS-PAGE.

<p>Lane 1: High Molecular Weight standard (kDa), lane 2: 0.5 μg MPO, lane 3–6: supernatant after centrifugation of 2 μg MPO (lanes 3 and 5) or 1 μg (lanes 4 and 6) mixed with 1 μl (1 mg) 60 nm PS-COOH (lanes 3 and 4) or with 1 μl H₂0 (lanes 5 and 6). Image J software was used to estimate the bands intensity and is represented as relative intensity for each lane (or relative quantity for each lane taking the first lane equal to 0.5μg/ml of MPO).</p

The size of TiO₂ particles in PBS or PBS with 10% serum.

<p>The peak diameter is defined as the diameter value where normalized absorbance is 1, and the half height peak width (H.h.p.w.) is defined as the difference between the two points where normalized absorbance is equal to 0.5.</p

Size of the 60 nm PS-COOH nanoparticles with or without MPO and MPO activity after removal of particles by centrifugation.

<p>Size of the 60 nm PS-COOH nanoparticles with or without MPO and MPO activity after removal of particles by centrifugation.</p

The effect of nanoparticles on purified MPO.

<p>Purified MPO in PBS was mixed with the different particles before the MPO activity was measured. The results are reported as % of MPO activity in samples without added nanoparticles. * p < 0,05 versus enzyme activity without NPs.</p

DataSheet_1_Immunization with nanovaccines containing mutated K-Ras peptides and imiquimod aggravates heterotopic pancreatic cancer induced in mice.zip

PurposeThe growing incidence and lethality of pancreatic cancer urges the development of new therapeutic approaches. Anti-tumoral vaccines can potentiate the immune response against the tumor, targeting specific antigens expressed only on tumor cells. In this work, we designed new vaccines for pancreatic cancer, composed by chitosan nanocapsules (CS NCs) containing imiquimod (IMQ) as adjuvant, and targeting the K-Ras mutation G12V.Experimental designWe tested the immunogenicity of our vaccines in mice, carrying different combinations of K-Ras mutated peptides. Then, we analyzed their prophylactic and therapeutic efficacy in mice bearing heterotopic pancreatic cancer.ResultsUnexpectedly, although good results were observed at short time points, the different combinations of our CS NCs vaccines seemed to potentiate tumor growth and reduce survival rate. We propose that this effect could be due to an inadequate immune response, partially because of the induction of a regulatory tolerogenic response.ConclusionOur results call for caution in the use of some NCs containing IMQ in the immunotherapy against pancreatic cancer.</p

Cyclodextrin-Modified Porous Silicon Nanoparticles for Efficient Sustained Drug Delivery and Proliferation Inhibition of Breast Cancer Cells

Over the past decade, the potential of polymeric structures has been investigated to overcome many limitations related to nanosized drug carriers by modulating their toxicity, cellular interactions, stability, and drug-release kinetics. In this study, we have developed a successful nanocomposite consisting of undecylenic acid modified thermally hydrocarbonized porous silicon nanoparticles (UnTHCPSi NPs) loaded with an anticancer drug, sorafenib, and surface-conjugated with heptakis­(6-amino-6-deoxy)-β-cyclodextrin (HABCD) to show the impact of the surface polymeric functionalization on the physical and biological properties of the drug-loaded nanoparticles. Cytocompatibility studies showed that the UnTHCPSi–HABCD NPs were not toxic to breast cancer cells. HABCD also enhanced the suspensibility and both the colloidal and plasma stabilities of the UnTHCPSi NPs. UnTHCPSi–HABCD NPs showed a significantly increased interaction with breast cancer cells compared to bare NPs and also sustained the drug release. Furthermore, the sorafenib-loaded UnTHCPSi–HABCD NPs efficiently inhibited cell proliferation of the breast cancer cells