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11 pages, 1915 KiB

Open AccessArticle

The Influence of Preforming Protein Coronas on the Performance of Dengue NS1 Immunoassays

by Hom Rijal, Laura Goggin, Rachel Muriph, Jason Evans and Kimberly Hamad-Schifferli

Pharmaceutics 2022, 14(11), 2439; https://doi.org/10.3390/pharmaceutics14112439 - 11 Nov 2022

Cited by 2 | Viewed by 1566

Abstract

The effect of preformed protein coronas on immunoassays for Dengue nonstructural protein 1 (NS1) immunoassays was investigated. The composition of the protein corona that forms around nanoparticle–antibody conjugates in human serum was characterized, and selected proteins from the corona were used for preformed coronas (human serum albumin and apolipoprotein A1). Coronas were formed and characterized by dynamic light scattering (DLS), and the nanoparticle-conjugate was probed by optical absorption spectroscopy. Immunoassays were run, and performance was quantified by analyzing the strip intensity as a function of NS1 concentration. The preformed coronas influenced the limit of detection (LOD) of the assay and the affinity for the NS1 target (K_D). The resulting K_D and LODs for the NP–Ab–ApoA1 immunoprobes were 0.83 nM and 1.24 nM, respectively. For the NP–Ab –HSA coronas, the test line intensity was lower by 33% at a given NS1 concentration than for the NP–Ab immunoprobes, and K_D was 0.14 nM, a slightly higher affinity. Due to the relatively large error of the negative control, a meaningful LOD for the NP–Ab with HSA coronas could not be determined. Full article

(This article belongs to the Special Issue Gold Nanoparticles for Biomedical Application)

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20 pages, 3320 KiB

Open AccessArticle

Cationic Polyethyleneimine (PEI)–Gold Nanocomposites Modulate Macrophage Activation and Reprogram Mouse Breast Triple-Negative MET-1 Tumor Immunological Microenvironment

by Vladimir Mulens-Arias, Alba Nicolás-Boluda, Florent Carn and Florence Gazeau

Pharmaceutics 2022, 14(10), 2234; https://doi.org/10.3390/pharmaceutics14102234 - 19 Oct 2022

Cited by 2 | Viewed by 2059

Abstract

Nanomedicines based on inorganic nanoparticles have grown in the last decades due to the nanosystems’ versatility in the coating, tuneability, and physical and chemical properties. Nonetheless, concerns have been raised regarding the immunotropic profile of nanoparticles and how metallic nanoparticles affect the immune system. Cationic polymer nanoparticles are widely used for cell transfection and proved to exert an adjuvant immunomodulatory effect that improves the efficiency of conventional vaccines against infection or cancer. Likewise, gold nanoparticles (AuNPs) also exhibit diverse effects on immune response depending on size or coatings. Photothermal or photodynamic therapy, radiosensitization, and drug or gene delivery systems take advantage of the unique properties of AuNPs to deeply modify the tumoral ecosystem. However, the collective effects that AuNPs combined with cationic polymers might exert on their own in the tumor immunological microenvironment remain elusive. The purpose of this study was to analyze the triple-negative breast tumor immunological microenvironment upon intratumoral injection of polyethyleneimine (PEI)–AuNP nanocomposites (named AuPEI) and elucidate how it might affect future immunotherapeutic approaches based on this nanosystem. AuPEI nanocomposites were synthesized through a one-pot synthesis method with PEI as both a reducing and capping agent, resulting in fractal assemblies of about 10 nm AuNPs. AuPEI induced an inflammatory profile in vitro in the mouse macrophage-like cells RAW264.7 as determined by the secretion of TNF-α and CCL5 while the immunosuppressor IL-10 was not increased. However, in vivo in the mouse breast MET-1 tumor model, AuPEI nanocomposites shifted the immunological tumor microenvironment toward an M2 phenotype with an immunosuppressive profile as determined by the infiltration of PD-1-positive lymphocytes. This dichotomy in AuPEI nanocomposites in vitro and in vivo might be attributed to the highly complex tumor microenvironment and highlights the importance of testing the immunogenicity of nanomaterials in vitro and more importantly in vivo in relevant immunocompetent mouse tumor models to better elucidate any adverse or unexpected effect. Full article

(This article belongs to the Special Issue Gold Nanoparticles for Biomedical Application)

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16 pages, 4246 KiB

Open AccessArticle

Combination of [¹⁷⁷Lu]Lu-DOTA-TATE Targeted Radionuclide Therapy and Photothermal Therapy as a Promising Approach for Cancer Treatment: In Vivo Studies in a Human Xenograft Mouse Model

by Marina Simón, Jesper Tranekjær Jørgensen, Harshvardhan A. Khare, Camilla Christensen, Carsten Haagen Nielsen and Andreas Kjaer

Pharmaceutics 2022, 14(6), 1284; https://doi.org/10.3390/pharmaceutics14061284 - 16 Jun 2022

Cited by 3 | Viewed by 2547

Abstract

Peptide receptor radionuclide therapy (PRRT) relies on α- and β-emitting radionuclides bound to a peptide that commonly targets somatostatin receptors (SSTRs) for the localized killing of tumors through ionizing radiation. A Lutetium-177 (¹⁷⁷Lu)-based probe linked to the somatostatin analog octreotate ([¹⁷⁷Lu]Lu-DOTA-TATE) is approved for the treatment of certain SSTR-expressing tumors and has been shown to improve survival. However, a limiting factor of PRRT is the potential toxicity derived from the high doses needed to kill the tumor. This could be circumvented by combining PRRT with other treatments for an enhanced anti-tumor effect. Photothermal therapy (PTT) relies on nanoparticle-induced hyperthermia for cancer treatment and could be a useful add-on to PRRT. Here, we investigate a strategy combining [¹⁷⁷Lu]Lu-DOTA-TATE PRRT and nanoshell (NS)-based PTT for the treatment of SSTR-expressing small-cell lung tumors in mice. Our results showed that the combination treatment improved survival compared to PRRT alone, but only when PTT was performed one day after [¹⁷⁷Lu]Lu-DOTA-TATE injection (one of the timepoints examined), showcasing the effect of treatment timing in relation to outcome. Furthermore, the combination treatment was well-tolerated in the mice. This indicates that strategies involving NS-based PTT as an add-on to PRRT could be promising and should be investigated further. Full article

(This article belongs to the Special Issue Gold Nanoparticles for Biomedical Application)

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