Effects of engineered nanoparticles on the innate immune system

Highlights

• Physicochemical properties of NPs affect interactions with innate immune system.

• Engineered NPs are effective for immunomodulation.

• Immunotoxicity assays of NPs are challenging.

Abstract

Engineered nanoparticles (NPs) have broad applications in industry and nanomedicine. When NPs enter the body, interactions with the immune system are unavoidable. The innate immune system, a non-specific first line of defense against potential threats to the host, immediately interacts with introduced NPs and generates complicated immune responses. Depending on their physicochemical properties, NPs can interact with cells and proteins to stimulate or suppress the innate immune response, and similarly activate or avoid the complement system. NPs size, shape, hydrophobicity and surface modification are the main factors that influence the interactions between NPs and the innate immune system. In this review, we will focus on recent reports about the relationship between the physicochemical properties of NPs and their innate immune response, and their applications in immunotherapy.

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.