Acute Immune Response of Micro- and Nanosized Erythrocyte-Derived Optical Particles in Healthy Mice
Autor: | Jenny T. Mac, Raviraj Vankayala, Taylor Hanley, David Lo, Bahman Anvari |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Lipopolysaccharides
Erythrocytes Lipopolysaccharide Pharmaceutical Science 02 engineering and technology 030226 pharmacology & pharmacy Theranostic Nanomedicine Macromolecular and Materials Chemistry chemistry.chemical_compound Mice 0302 clinical medicine Blood serum Models Immunologic Drug Discovery Pharmacology & Pharmacy Drug Carriers Chemistry Liver Disease Interleukin Pharmacology and Pharmaceutical Sciences 021001 nanoscience & nanotechnology delivery systems folate receptor medicine.anatomical_structure Liver Folate receptor Injections Intravenous Models Animal Molecular Medicine Cytokines Tumor necrosis factor alpha Female Intravenous 0210 nano-technology medicine.medical_specialty Infrared Rays Dose-Response Relationship Immunologic Spleen Article Drug Administration Schedule Injections Dose-Response Relationship 03 medical and health sciences Immune system Internal medicine medicine Animals Particle Size Animal Immunity Phototherapy cytokines Endocrinology HER-2 innate immune response Nanoparticles Particle size Digestive Diseases red blood cells |
Zdroj: | Mol Pharm Molecular pharmaceutics, vol 17, iss 10 |
Popis: | Erythrocyte-derived particles activated by near-infrared (NIR) light present a platform for various phototheranostic applications. We have engineered such a platform with indocyanine green as the NIR-activated agent. A particular feature of these particles is that their diameters can be tuned from micro- to nanoscale, providing a potential capability for broad clinical utility ranging from vascular to cancer-related applications. An important issue related to clinical translation of these particles is their immunogenic effects. Herein, we have evaluated the early-induced innate immune response of these particles in healthy Swiss Webster mice following tail vein injection by measurements of specific cytokines in blood serum, the liver, and the spleen following euthanasia. In particular, we have investigated the effects of particle size and relative dose, time-dependent cytokine response for up to 6 h postinjection, functionalization of the nanosized particles with folate or Herceptin, and dual injections of the particles 1 week apart. Mean concentrations of interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α, and monocyte chemoattractant protein (MCP)-1 in response to injection of microsized particles at the investigated relative doses were significantly lower than the corresponding mean concentrations induced by lipopolysaccharide (positive control) at 2 h. All investigated doses of the nanosized particles induced significantly higher concentrations of MCP-1 in the liver and the spleen as compared to phosphate buffer saline (PBS) (negative control) at 2 h. In response to micro- and nanosized particles at the highest investigated dose, there were significantly higher levels of TNF-α in blood serum at 2 and 6 h postinjection as compared to the levels associated with PBS treatment at these times. Whereas the mean concentration of TNF-α in the liver significantly increased between 2 and 6 h postinjection in response to the injection of the microsized particles, it was significantly reduced during this time interval in response to the injection of the nanosized particles. In general, functionalization of the nanosized particles was associated with a reduction of IL-6 and MCP-1 in blood serum, the liver, and the spleen, and TNF-α in blood serum. With the exception of IL-10 in the spleen in response to nanosized particles, the second injection of micro- or nanosized particles did not lead to significantly higher concentrations of other cytokines at the investigated dose as compared to a single injection. |
Databáze: | OpenAIRE |
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