Functionalization of polyanhydride microparticles with di-mannose influences uptake by and intracellular fate within dendritic cells

Phanse, Yashdeep; Carrillo-Conde, Brenda; Ramer‐Tait, Amanda E.; Roychoudhury, Rajarshi; Pohl, Nicola L. B.; Narasimhan, Balaji; Wannemuehler, Michael J.; Bellaire, Bryan H.

doi:10.1016/j.actbio.2013.06.024

Cited by 44 publications

(41 citation statements)

References 38 publications

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“…Our previous work has shown that amphiphilic nanoparticle chemistries were suitable for protein stabilization (16,24,28,38,39), demonstrated potent adjuvant responses (20), and were effectively internalized by and activated APCs (6,17,24,40). Therefore, the 50:50 CPTEG:CPH nanoparticle formulation was chosen to perform the carbohydrate functionalization and to evaluate safety upon in vivo administration.…”

Section: Functionalization and Characterization Of Carbohydrate-modifmentioning

confidence: 99%

“…C a r b o x y m e t h y l -α -D -m a n n o p y r a n o s y l -( 1 , 2 ) -Dmannopyranoside and carboxymethyl-β-galactoside were conjugated onto the surface of polyanhydride nanoparticles using an amine-carboxylic acid coupling reaction (6,17,18,24). Particles with glycolic acid groups on the surface (linker) and non-functionalized (NF) particles were used as controls.…”

Section: Surface Functionalizationmentioning

confidence: 99%

“…In previous in vitro studies, it was demonstrated that dimannose functionalization of polyanhydride nanoparticles, which would induce signaling via C-type lectin receptors (CLRs) on APCs, enhanced the activation of macrophages and dendritic cells (DCs) (6,17,18,24). Because of the role of CLR signaling in stimulating innate immunity, identifying safe and effective means to selectively target APC receptors such as the macrophage mannose receptor (MMR) and the macrophage galactose binding lectin (MGL) will provide novel approaches to enhance and shape adaptive immunity (3,25,26).…”

Section: Introductionmentioning

confidence: 99%

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Safety and Biocompatibility of Carbohydrate-Functionalized Polyanhydride Nanoparticles

Vela-Ramirez

Goodman

Boggiatto

et al. 2014

AAPS J

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ABSTRACT. Carbohydrate functionalization of nanoparticles allows for targeting of C-type lectin receptors. This family of pattern recognition receptors expressed on innate immune cells, such as macrophages and dendritic cells, can be used to modulate immune responses. In this work, the in vivo safety profile of carbohydrate-functionalized polyanhydride nanoparticles was analyzed following parenteral and intranasal administration in mice. Polyanhydride nanoparticles based on 1,6-bis-(pcarboxyphenoxy)hexane and 1,8-bis-(p-carboxyphenoxy)-3,6-dioxaoctane were used. Nanoparticle functionalization with di-mannose (specifically carboxymethyl-α-D-mannopyranosyl-(1,2)-Dmannopyranoside), galactose (specifically carboxymethyl-β-galactoside), or glycolic acid induced no adverse effects after administration based on histopathological evaluation of liver, kidneys, and lungs. Regardless of the polymer formulation, there was no evidence of hepatic or renal damage or dysfunction observed in serum or urine samples. The histological profile of cellular infiltration and the cellular distribution and kinetics in the lungs of mice administered with nanoparticle treatments followed similar behavior as that observed in the lungs of animals administered with saline. Cytokine and chemokine profiles in bronchoalveolar lavage fluid indicated surface chemistry dependence on modest secretion of IL-6, IP-10, and MCP-1; however, there was no evidence of any deleterious histopathological changes. Based on these analyses, carbohydrate-functionalized nanoparticles are safe for in vivo applications. These results provide foundational information towards the evaluation of the capabilities of these surface-modified nanoparticles as vaccine delivery formulations.

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Section: Functionalization and Characterization Of Carbohydrate-modifmentioning

confidence: 99%

Section: Surface Functionalizationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Safety and Biocompatibility of Carbohydrate-Functionalized Polyanhydride Nanoparticles

Vela-Ramirez

Goodman

Boggiatto

et al. 2014

AAPS J

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“…Tzianabos et al (10) and Cobb et al (11) were the first to describe CD4 ϩ T cell proliferation mediated by zwitterionic polysaccharides of Bacteroides fragilis, which indicated that some carbohydrates can function as antigens without attachment to a lipid or protein. This property of carbohydrates has led to interest in the mechanisms of how pathogen-derived carbohydrates modulate host immune responses, resistance to treatment (12), and their potential role in novel therapeutic drug delivery methods (13,14). Our laboratories have focused on the role of oligosaccharides in alteration of the innate and adaptive responses during infection using the protozoan parasite Leishmania as a model organism (15)(16)(17).…”

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confidence: 99%

Leishmania-Derived Trimannose Modulates the Inflammatory Response To Significantly Reduce Leishmania major-Induced Lesions

et al. 2018

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Leishmania lipophosphoglycan (LPG) is a key virulence factor, initiating inflammation resulting in cutaneous lesions. LPG is capped by various oligosaccharides. How these glycans are recognized and how they alter the course of Leishmania infection are poorly understood. Previous studies synthesized ␣-1,2-trimannose cap sugars on latex beads and demonstrated that C57BL/6 mice coinoculated with Leishmania major and trimannose-coated beads produced significantly higher levels of interleukin-12p40 (IL-12p40) and other proinflammatory, type 1 cytokines than mice inoculated with L. major alone within the first 48 h of infection. However, as L. major infection typically progress over weeks to months, the role of trimannose in altering disease progression over the course of infection was unknown. Wild-type mice were inoculated with either trimannose-coated or carrier (uncoated) beads, infected with L. major alone, coinoculated with carrier beads and L. major, or coinoculated with trimannose-coated beads and L. major. Trimannose treatment of L. majorinfected mice decreased the parasite load and significantly decreased the lesion size at 14 days postinfection (p.i.) compared to results for nontreated, infected mice. Infected, trimannose-treated mice had decreased IL-12p40 and IL-10 secretion and increased interferon gamma secretion at 14 days p.i. Mannose receptor knockout (MR Ϫ/Ϫ ) mice lack the ability to detect trimannose. When MR Ϫ/Ϫ mice were infected with L. major and treated with trimannose beads, they did not have decreased lesion size. Leishmania-derived trimannose represents a novel immunomodulator that provides early type 1-skewed cytokine production to control the parasite load and alter the course of cutaneous leishmaniasis.KEYWORDS Leishmania, carbohydrate, cutaneous leishmaniasis, mannose receptor G lycoconjugate cell surface molecules of many pathogens are often key virulence factors that promote pathogen survival (1-5). Antigen glycosylation has become increasingly recognized as a critical component of immune modulation by pathogens (6-9). However, the glycan portion of the glycoconjugate was mainly considered a modulatory component with little to no antigenic properties independent of the lipid or protein that it was conjugated to. Tzianabos et al. (10) and Cobb et al. (11) were the first to describe CD4 ϩ T cell proliferation mediated by zwitterionic polysaccharides of Bacteroides fragilis, which indicated that some carbohydrates can function as antigens without attachment to a lipid or protein. This property of carbohydrates has led to interest in the mechanisms of how pathogen-derived carbohydrates modulate host immune responses, resistance to treatment (12), and their potential role in novel

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“…222 224 225 231 A recent advancement in nanovaccines is the ability to target these vaccines to specific tissues by functionalizing the particles with carbohydrate ligands to enable C-type lectin receptor-mediated uptake, which may enable more efficient delivery of antigen to APCs. [309][310][311] Finally, some specific polyanhydride nanoparticle formulations have demonstrated enhanced thermal stability at room temperature (i.e., break the cold chain requirement) over several months, suggesting that nanovaccines may be stored at room temperature for long periods of time, 312 which has important implications for stockpiling and preparedness for pandemic situations. In addition, the ability to confer long-lived immunity in a single dose will enhance patient compliance.…”

Section: Novel Nano-adjuvants and Delivery Vehiclesmentioning

confidence: 98%

Vaccine Technologies Against Avian Influenza: Current Approaches and New Directions

Ross¹,

Lm²,

Je³

et al. 2014

j biomed nanotechnol

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The potential epidemiological human pandemic resulting from highly pathogenic avian influenza (HPAI) H5N1 has been studied extensively since the identification of the virus in the Guangdong province of China. The majority of research has focused on the unique and severe histopathological lesions induced by the virus. The severe pathological presentation of these infections has also prompted interest in identifying preventive and therapeutic approaches against HPAI. The potential severity of a HPAI pandemic and the efforts to identify effective intervention strategies have led to many novel discoveries in vaccine and antiviral development that are critically examined in this review.

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Functionalization of polyanhydride microparticles with di-mannose influences uptake by and intracellular fate within dendritic cells

Cited by 44 publications

References 38 publications

Safety and Biocompatibility of Carbohydrate-Functionalized Polyanhydride Nanoparticles

Safety and Biocompatibility of Carbohydrate-Functionalized Polyanhydride Nanoparticles

Leishmania-Derived Trimannose Modulates the Inflammatory Response To Significantly Reduce Leishmania major-Induced Lesions

Vaccine Technologies Against Avian Influenza: Current Approaches and New Directions

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