ReviewEffects of engineered nanoparticles on the innate immune system
Introduction
Due to their unique physical and chemical properties, Nanoparticles (NPs) are widely used in electronics, cosmetics, textiles and nanomedicine [1], [2], [3], [4], [5]. At present, human exposure to engineered NPs is widespread, through environmental routes (inhalation, ingestion, dermal contact and parenteral) or deliberate administration [6], [7]. Interactions between nanoparticles(NPs) and the immune system have become important, and there are foundational questions about the safety of these special materials. NPs can communicate with various biological components (cells, receptors, proteins etc.) of the immune system, trigger cell signaling cascades, and consequently cause unpredictable immune responses (activation or suppression) and even harmful outcomes (autoimmune diseases or cancer) [5], [7], [8]. There is also evidence that NPs can alter the development of immune systems in utero in mouse models. [9]. Therefore, understanding how NPs influence or tune the immune system is critical to better knowing the potential risks in developing new nanomaterials.
The basic concept of the immune system is a biological network that reacts to foreign threats (i.e. antigens) to protect the host and maintain homeostasis [5]. The overall system is divided into two subsystems: innate immunity and adaptive immunity. Innate immunity is the first line of defense, generating a non-specific inflammatory response upon the detection of conserved biological motifs, often associated with bacteria and viruses. The adaptive immune system is a more nuanced defense mechanism that involves the development of antibodies highly-specific to detected antigens, followed by the generation of memory cells for future immunological protection [10]. Components of the innate immune system recognize pathogens mainly via pattern-recognition receptors (PRPs), while antigen presenting cells (APCs) present acquired antigens to T cells for the activation of acquired immune system. When NPs enter the body, they have a high probability of interacting with the innate immune system first, generating an immunomodulatory response based on their physicochemical properties [8], [11]. Hence, understanding how NPs interact with the innate immune system is particularly important, and would provide insight into designing immune-compatible NP technologies.
Engineered NPs can be designed to either specifically interact with or avoid recognition by the immune system. Synthetic NPs have been utilized frequently to generate novel immunotherapy strategies. Immunotherapy involves intentional modulation of the immune system as a therapeutic strategy. One of the primary strengths of immunotherapy is that there can be less negative side effects than those associated with traditional therapies [12], [13]. A frequent use for NPs in immunotherapy contexts has been for developing new vaccines, which has been previously discussed [14], [15], [16], [17], [18]. Here, we will focus on understanding the interactions between the innate immune system and engineered NPs for other immunomodulatory purposes. First, we will discuss how physicochemical properties of NPs affect the contact of NPs with the innate immune system and the resulting immune response. Then, we will demonstrate how to take advantage of NPs immunomodulatory properties for biological applications. At last, we will discuss remaining challenges that need to be considered for NP applications.
Section snippets
Innate immune system
The innate immune system is a broad, less-specific defense mechanism, which includes molecular (complement system, cytokines) and cellular (phagocytes and leukocytes) components that recognize classes of molecules particular to frequently encountered pathogens. Most components of the innate immune system are present before the onset of the infection and rapidly respond to invasion within minutes. In conjunction with this system is the highly organized complement system, which involves a set of
Physicochemical properties of nanoparticles modulate innate immune response
NPs have been prepared with a variety of controlled structures and functionalities for delivery, therapeutic, and diagnostic purposes. Once inside the body, engineered NPs as foreign substance are immediately encounter the innate immune system and generate specific immune response based on their properties. The physicochemical properties (e.g. size, charge, shape, hydrophobicity, and stiffness) of NPs determine their interactions with soluble proteins, APCs and neutrophils, in particular effect
Therapeutic immune modulation by engineered nanoparticles
Engineered NPs acting as delivery vehicles or direct immunomodulation agents can manipulate the innate immune system for therapeutic purposes. The main two applications areas are vaccination and cancer immunotherapy, which both “train” the immune system to detect and eliminate foreign entities or tumors. The key to these therapeutic strategies is to induce the desired immune response (stimulation or suppression) through the recognition of engineered NPs by the innate immune system, especially
Current challenges and perspective
Despite the potential benefits of using NPs in industry and medicine, concerns about the biosafety of these materials have not abated. Interactions between engineered NPs and different subsets of the innate immune system have become critical questions that need to be answered. These interactions can generate varied immunological responses to modulate the immune system and may cause immunotoxicity. For example, NPs create more ROS in cells in a pro-inflammatory state, which can induce protein,
Conclusion
Studies have shown that nanoparticles can interact with components of the innate immune system to various immunological endpoints. These interactions are fast, complex, and not well understood. It has been established that NPs’ physicochemical properties (size, shape, hydrophobicity and surface modification) are key to determining their interactions with plasma proteins and immune cells, especially APCs. NPs can absorb proteins on their surfaces once they enter the bloodstream, and these
Acknowledgment
V.M.R. acknowledges support from the NIH (GM077173 and EB022641).
References (107)
- et al.
A review on the application of inorganic nano-structured materials in the modification of textiles: focus on anti-microbial properties
Colloids Surf. B Biointerfaces
(2010) - et al.
Current understanding of interactions between nanoparticles and the immune system
Toxicol. Appl. Pharmacol.
(2016) - et al.
Nanotechnology in vaccine delivery
Adv. Drug Deliv. Rev.
(2008) - et al.
Nanoparticle vaccines
Vaccine
(2014) - et al.
Overview on experimental models of interactions between nanoparticles and the immune system
Biomed. Pharmacother.
(2016) - et al.
Altering the immune response with lipid-based nanoparticles
J. Controlled Release
(2012) - et al.
Harnessing nanoparticles for immune modulation
Trends Immunol.
(2015) - et al.
Biodistribution of colloidal gold nanoparticles after intravenous administration: effect of particle size
Colloids Surf. B Biointerfaces
(2008) - et al.
Immunomodulatory effects of coated gold nanoparticles in LPS-stimulated in vitro and in vivo murine model systems
Chemistry
(2016) - et al.
Enhanced antigen presentation and immunostimulation of dendritic cells using acid-degradable cationic nanoparticles
J. Controlled Release
(2005)