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
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