Effect of Surface Modification and Macrophage Phenotype on Particle Internalization

Abstract

Material properties play a key role in the cellular internalization of polymeric particles. In the present study, we have investigated the effects of material characteristics such as water contact angle, zeta potential, melting temperature, and alternative activation of complement on particle internalization for pro-inflammatory, pro-angiogenic, and naïve macrophages by using biopolymers (∼600 nm), functionalized with 13 different molecules. Understanding how material parameters influence particle internalization for different macrophage phenotypes is important for targeted delivery to specific cell populations. Here, we demonstrate that material parameters affect the alternative pathway of complement activation as well as particle internalization for different macrophage phenotypes. Here, we show that the quantitative structure-activity relationship method (QSAR) previously used to predict physiochemical properties of materials can be applied to targeting different macrophage phenotypes. These findings demonstrated that targeted drug delivery to macrophages could be achieved by exploiting material parameters.

Macrophage silica nanoparticle response is phenotypically dependent

“…Evidence suggests variations in nanomaterial properties can alter macrophage uptake and initiate either Th1 or Th2 responses[13]. Clinically, environmental exposure to nanomaterials correlates directly to induced autoimmune disorders such as scleroderma and rheumatoid arthritis[14, 15].…”

Liquid Metal Phagocytosis: Intermetallic Wetting Induced Particle Internalization

“…Recently, self‐powered motor,11 jumper,12 oscillator,13 soft actuators,14, 15, 16 and 2D semiconductor skin17 demonstrated with this class of material shed light on their new possibilities toward more diverse applications. Here, we report a particle‐eating phenomenon of gallium‐based LMs, which mimics the biological phagocytosis process (also known as cellular‐eating, a basic cell behavior referring to the transportation of external particles into cells from across the membranes18, 19, 20, 21), and thus we call it LM‐Phagocytosis. Such phenomenon represents a wet‐processing strategy to achieve particle internalization.…”

pH responsive gels that deliver anti-inflammatory drugs

“…While cell viability was not linearly correlated with the descriptors or observables measured here, cell internalization was positively correlated with PEG molecular weight (R = 0.87) and was not correlated with alkyl chain length (R = -0.18). Since the length of PEG is related to its hydrogen bonding capability, and this is known to influence macrophage internalization, 242 this result was expected. Furthermore, the alkyl chain is in the interior of the particle and would not be expected to interact with the cell at concentrations above the…”

“…Developing design principles for these systems remains a critical challenge for researchers in drug delivery. Some methods that have been used for developing such principles for drug delivery include mathematical models, such as quantitative structure-activity relationships, 242,243 or statistical methods to determine materials properties that influence outcomes, such as principal component analysis. [244][245][246][247][248][249][250] Here, we employ factorial analysis, which uses linear relationships between materials properties to develop a prediction for an outcome.…”

“…Polymer properties influence particle internalization by macrophages. [254][255][256] Macrophages derive from monocytes and maintain a unique role in innate immunity, 58 adaptive immunity, and tumor angiogenesis and migration. 56 In this research, Ppeg modified with bromoalkanes with chain lengths from C6 to C11 were synthesized.…”