Design of Polymeric Nanocapsules to Improve Their lympho-targeting Capacity

Crecente‐Campo, José; Virgilio, Tommaso; Morone, Diego; Calviño-Sampedro, Cristina; Fernández‐Mariño, Iago; Ana, Olivera; Varela-Calviño, Rubén; González, Santiago F.; Alonso, María José

doi:10.2217/nnm-2019-0206

Cited by 16 publications

(10 citation statements)

References 69 publications

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“…4c, suggest a preferential interaction of both types of nanoparticles with DCs. This is in accordance with our recent study with polymeric nanocapsules subcutaneously administered to mice, in which we observed a similar trend of preferential interaction with DCs [57]. This preferential interaction was particularly striking in the case of OVA-NP, which may be related to the specialized ability of DCs to recognize different types of antigens.…”

Section: Biodistribution Of Cs:cmβg Nanoparticles In the Lymphatic Systemsupporting

confidence: 93%

“…Popliteal LN were collected 12 h post-administration. It is worth mentioning that at this time point phagocytes are the first cells to encounter the antigen transported by the lymph, so, in line with previous results obtained in our group [57], we expected the main interaction of the particles to be with APCs and not with follicular B cells.…”

Section: Biodistribution Of Cs:cmβg Nanoparticles In the Lymphatic Systemsupporting

confidence: 86%

“…4b). As previously mentioned, the size and surface charge of the nanoparticles [29,53,57], as well as the ability of CMβG to interact with complement receptor 3 (CR3) and Dectin-1 receptor present in APCs [20][21][22], could explain this positive biodistribution profile.…”

Section: Biodistribution Of Cs:cmβg Nanoparticles In the Lymphatic Systemmentioning

confidence: 95%

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Carboxymethyl-β-glucan/chitosan nanoparticles: new thermostable and efficient carriers for antigen delivery

Cordeiro

Farsakoglu

Crecente‐Campo

et al. 2021

Drug Deliv. and Transl. Res.

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In the last few decades, nanotechnology has emerged as an important tool aimed at enhancing the immune response against modern antigens. Nanocarriers designed specifically for this purpose have been shown to provide protection, stability, and controlled release properties to proteins, peptides, and polynucleotide-based antigens. Polysaccharides are particularly interesting biomaterials for the construction of these nanocarriers given their wide distribution among pathogens, which facilitates their recognition by antigen-presenting cells (APCs). In this work, we focused on an immunostimulant beta-glucan derivative, carboxymethyl-β-glucan, to prepare a novel nanocarrier in combination with chitosan. The resulting carboxymethyl-β-glucan/ chitosan nanoparticles exhibited adequate physicochemical properties and an important protein association efficiency, with ovalbumin as a model compound. Moreover, thermostability was achieved through the optimization of a lyophilized form of the antigen-loaded nanoparticles, which remained stable for up to 1 month at 40 ºC. Biodistribution studies in mice showed an efficient drainage of the nanoparticles to the nearest lymph node following subcutaneous injection, and a significant colocalization with dendritic cells. Additionally, subcutaneous immunization of mice with a single dose of the ovalbumin-loaded nanoparticles led to induced T cell proliferation and antibody responses, comparable to those achieved with alum-adsorbed ovalbumin. These results illustrate the potential of these novel nanocarriers in vaccination.

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Section: Biodistribution Of Cs:cmβg Nanoparticles In the Lymphatic Systemsupporting

confidence: 93%

Section: Biodistribution Of Cs:cmβg Nanoparticles In the Lymphatic Systemsupporting

confidence: 86%

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Carboxymethyl-β-glucan/chitosan nanoparticles: new thermostable and efficient carriers for antigen delivery

Cordeiro

Farsakoglu

Crecente‐Campo

et al. 2021

Drug Deliv. and Transl. Res.

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“…Similarly, the development of drugs capable of targeting specifically SSM might reveal useful to block the IL-1α -STAT3 axis only in these cells and to boost their anti-tumoral properties, in a process of macrophages repolarization 75 . Unfortunately, despite recent studies described compounds capable of localizing differentially in the SCS and in the medullary area of the LN, a therapy able to differentiate specifically macrophage subsets in the LN is still missing 72,76,77 .…”

Section: Discussionmentioning

confidence: 99%

IL-1α secreted by subcapsular sinus macrophages promotes melanoma metastasis in the sentinel lymph node by upregulating STAT3 signaling in the tumor

Virgilio

Bordini

Sartori

et al. 2021

Preprint

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During melanoma metastasization, tumor cells originated in the skin migrate via lymphatic vessels to the sentinel lymph node (sLN) in a process that facilitates their spread across the body. Here, we characterized the innate inflammatory responses to melanoma metastasis in the sLN. For this purpose, we confirmed the migration of fluorescent metastatic melanoma cells to the sLN and we characterized the inflammatory response in the metastatic microenvironment. We found that macrophages located in the subcapsular sinus (SSM), produce pro-tumoral IL-1α after recognition of tumor antigens. Moreover, we confirmed that the administration of an anti-IL-1α depleting antibody reduced metastasis. Conversely, the administration of recombinant IL-1α accelerated the lymphatic spreading of the tumor. Additionally, the elimination of the macrophages significantly reduced the progression of the metastatic spread. To understand the mechanism of action of IL-1α in the context of the lymph node microenvironment, we applied single-cell RNA sequencing to dissected metastases obtained from animals treated with an anti-IL-1α blocking antibody. Amongst the different pathways affected, we identified STAT3 as one of the main targets of IL-1α signaling in metastatic cells. Moreover, we found that the anti-IL-1α anti-tumoral effect was not mediated by lymphocytes, as IL-1R1 KO mice did not show any improvement in metastasis growth. Finally, we found a synergistic anti-metastatic effect of the combination of IL-1α blocking and the STAT3 inhibitor (STAT3i) stattic. In summary, we described a new mechanism by which SSM support melanoma metastasis, highlighting a new target for immunotherapy.

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“…These results were in line with previous findings regarding the higher toxicity of pArg NCs than CS NCs [ 5 , 11 ]. On the other hand, INU NCs, without the pArg layer, showed considerably lower toxicities [ 53 , 54 ]. In addition, the higher IMQ content in the INU/pArg NCs could also be related with the increased toxicity [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

Design of Polymeric Nanocapsules for Intranasal Vaccination against Mycobacterium Tuberculosis: Influence of the Polymeric Shell and Antigen Positioning

et al. 2020

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Tuberculosis (TB) is the leading cause of death from a single infectious microorganism and Bacillus Calmette Guerin (BCG), the only authorized vaccine, does not confer protection against pulmonary TB. Based on the hypothesis that mucosal protection could help to prevent the infection at the site of entrance, the objective of this work was to develop an intranasal vaccine against Mycobacterium tuberculosis (Mtb), the microorganism that causes TB. Our approach consisted of the use of polymeric nanocapsules (NCs) with an oily core and a polymer shell made of chitosan (CS) or inulin/polyarginine (INU/pArg). The immunostimulant Imiquimod, a Toll-like receptor-7 (TLR-7) agonist, was encapsulated in the oily core and a fusion protein, formed by two antigens of Mtb, was absorbed either onto the NC surface (CS:Ag and INU:pArg:Ag) or between two polymer layers (INU:Ag:pArg) in order to assess the influence of the antigen positioning on the immune response. Although CS NCs were more immunostimulant than the INU/pArg NCs in vitro, the in vivo experiments showed that INU:pArg:Ag NCs were the only prototype inducing an adequate immunoglobulin A (IgA) response. Moreover, a previous immunization with BCG increased the immune response for CS NCs but, conversely, decreased for INU/pArg NCs. Further optimization of the antigen and the vaccination regime could provide an efficacious vaccine, using the INU:pArg:Ag NC prototype as nanocarrier.

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Design of Polymeric Nanocapsules to Improve Their lympho-targeting Capacity

Cited by 16 publications

References 69 publications

Carboxymethyl-β-glucan/chitosan nanoparticles: new thermostable and efficient carriers for antigen delivery

Carboxymethyl-β-glucan/chitosan nanoparticles: new thermostable and efficient carriers for antigen delivery

IL-1α secreted by subcapsular sinus macrophages promotes melanoma metastasis in the sentinel lymph node by upregulating STAT3 signaling in the tumor

Design of Polymeric Nanocapsules for Intranasal Vaccination against Mycobacterium Tuberculosis: Influence of the Polymeric Shell and Antigen Positioning

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