A Bird's Eye View of Various Cell-Based Biomimetic Nanomedicines for the Treatment of Arthritis

Abstract

Arthritis is the inflammation and tenderness of the joints because of some metabolic, infectious, or constitutional reasons. Existing arthritis treatments help in controlling the arthritic flares, but more advancement is required to cure arthritis meticulously. Biomimetic nanomedicine represents an exceptional biocompatible treatment to cure arthritis by minimizing the toxic effect and eliminating the boundaries of current therapeutics. Various intracellular and extracellular pathways can be targeted by mimicking the surface, shape, or movement of the biological system to form a bioinspired or biomimetic drug delivery system. Different cell-membrane-coated biomimetic systems, and extracellular-vesicle-based and platelets-based biomimetic systems represent an emerging and efficient class of therapeutics to treat arthritis. The cell membrane from various cells such as RBC, platelets, macrophage cells, and NK cells is isolated and utilized to mimic the biological environment. Extracellular vesicles isolated from arthritis patients can be used as diagnostic tools, and plasma or MSCs-derived extracellular vesicles can be used as a therapeutic target for arthritis. Biomimetic systems guide the nanomedicines to the targeted site by hiding them from the surveillance of the immune system. Nanomedicines can be functionalized using targeted ligand and stimuli-responsive systems to reinforce their efficacy and minimize off-target effects. This review expounds on various biomimetic systems and their functionalization for the therapeutic targets of arthritis treatment, and discusses the challenges for the clinical translation of the biomimetic system.

Keywords: arthritis; bioinspired; biomimetics; membrane-coated; nanoparticles; stimuli-responsive.

Figure 1

Pathophysiology of Rheumatoid Arthritis. (A) The immune system interprets citrulline-containing regions of a number of proteins as foreign antigens, and the APCs subsequently take these antigens up. (B) The APCs are transported to the lymph nodes, where the T cells are stimulated and develop into B cells and T helper cells. (C) The lymphocytes go through the circulatory system to the joint region. (D) In the meantime, the T effector cells release pro-inflammatory mediators that, through a cascade of events of other inflammatory mediators, cause joint inflammation, an increase in pain receptors, and bone loss. All these events eventually cause the development of arthritis. APC: antigen-presenting cell; IFN: interferon; TNF: tumour necrosis factor; RF: rheumatoid factor; ACCP: anti-cyclic citrullinated peptides; GM-CSF: granulocyte–macrophage colony-stimulating factor; RANKL: receptor activator for nuclear factor κ B ligand; MMP: matrix metalloproteinases.

Figure 2

Overview of the isolation of cell membrane.

Figure 3

Isolation of the cell membrane from different types of the cells such as nucleus-containing cells, nucleus-free cells, and organelles.

Figure 4

Role of extracellular vesicles in the diagnosis and treatment of arthritis.

Figure 5

Isolation of exosomes.

Figure 6

DiD-labelled formulation in vivo biodistribution. (a) Mice imaging with CIA at various time points after IV injection with DiD/M2 Exo, DiD/M0 Exo, free DiD (n = 3). (b) Ankle joint analysis of fluorescence intensity. * p < 0.05, ** p < 0.01, **** p < 0.0001. (c) DiD labelled and free DiD formulations’ biodistribution in blood as well as different organs after 72 h of injection. (d) Quantitative evaluation of M2 Exo/pDNA/BSP therapeutic efficacy in CIA mice showing the establishment of RA and treatment procedure. Measurement of (e) body weight and (f) average articular score. *** p < 0.001, **** p < 0.0001.(g) Images of mice hind legs both before and after treatment with numerous formulations of drugs. Adapted from [92] with permission.

Figure 7

PNPs in vivo and ex vivo imaging in CIA mice. (a) NIRF imaging in vivo of arthritic (right) and non-arthritic (left) paws from CIA mice (n = 3) at various times following intravenous injection. (b) Inflamed right paw fluorescence images with only one arthritic toe. (c) NIRF imaging ex vivo of major organs after 24 h of nanoparticle injection. (d) Major organs mean NIRF intensity (n = 3; mean ± SD), p < 0.05 compared to a solution or the NP group. (e) Twenty-four-hour post-injection inflamed paws ex vivo NIRF image from the NP as well as PNP groups. (f) Paw inflammation intensity as measured by mean NIRF (n = 3; mean SD), * p < 0.05 vs. solution and NP groups. (g) CIA mice therapeutic efficacy. Average rheumatoid arthritis index as a function of the time since the first immunization, * p < 0.05. (h) Micro-CT data of hind paw quantitative analysis. (i) Hind paw representative pictures from CIA mice in various treatment groups as well as normal mice that did not receive any treatment. (j) Mice with and without CIA were studied using micro-CT scans of their hind paws, and the results were reconstructed in three dimensions. Adapted from [103] with permission under license CC-BY.

Figure 8

Isolation of platelet and membrane derivation.

Figure 9

Biomimetic nanomedicines with targeting ligands.

Figure 10

Stimuli-responsive biomimetic nanomedicines.