Engineering white blood cell membrane-camouflaged nanocarriers for inflammation-related therapeutics

Abstract

White blood cells (WBCs) play essential roles against inflammatory disorders, bacterial infections, and cancers. Inspired by nature, WBC membrane-camouflaged nanocarriers (WBC-NCs) have been developed to mimic the "dynamic" functions of WBCs, such as transendothelial migration, adhesion to injured blood vessels, etc, which make them promising for diverse medical applications. WBC-NCs inherit the cell membrane antigens of WBCs, while still exhibiting the robust inflammation-related therapeutic potential of synthetic nanocarriers with excellent (bio)physicochemical performance. This review summarizes the proposed concept of cell membrane engineering, which utilizes physical engineering, chemical modification, and biological functionalization technologies to endow the natural cell membrane with abundant functionalities. In addition, it highlights the recent progress and applications of WBC-NCs for inflammation targeting, biological neutralization, and immune modulation. Finally, the challenges and opportunities in realizing the full potential of WBC-NCs for the manipulation of inflammation-related therapeutics are discussed.

Keywords: Biological neutralization; Immune modulation; Inflammation targeting; White blood cell membrane-camouflaged nanocarriers.

Graphical abstract

Fig. 1

The analysis of keyword co-occurrences on white blood cell membrane, nanocarriers, inflammation, active targeting, neutralization, and immune modulation.

Fig. 2

Strategies for cell membrane physical engineering. (A) Schematic representation of MΦ-NP(L&K) designed to inhibit PLA2 during AP progression [53]. (B) Schematic representation of preparation process of [RBC-P]NPs [54].

Fig. 3

Strategies for cell membrane chemical modification and schematic illustration of the fabrication of biomimetic aAPC for T-cell-based anticancer therapy [58].

Fig. 4

Strategies for cell membrane biological functionalization. (A) The fabrication and application of Sa-M-GSNCs. Sa-M-GSNCs were fabricated through coating S. aureus pretreated MM onto GSNCs [63]. (B) Application of Sa-M-GSNCs by local and systemic injection [63]. (C) Schematic fabrication of VLA-4 NPs for active-targeting drug delivery to inflamed lung endothelial cells [65].

Fig. 5

(A) Preparation of Me-ANPs and the schematic diagram of the hypothetical mechanism of Me-ANPs killing intracellular bacterial pathogens hidden in WBCs. (B) The relative abundance of TLRs on J774A.1 membranes and Me-ANP. (C)In vivo antimicrobial efficacy of mouse J774A.1 treated with PBS, ciprofloxacin, ANPs, and Me-ANPs [38].

Fig. 6

(A) Preparation of MM/RAPNP and its mechanism to treat AS. (B) Typical photographs of Oil Red O-stained aortas and quantitative analysis of the diseased region after being treated with free RAP, RAPNPs, and MM/RAPNP. (C) Oil Red O-stained cross-sections of the aortic root and its quantitative analysis of the lipid deposition area after being treated with free RAP, RAPNPs, and MM/RAPNP [85].

Fig. 7

(A) Preparation of the Dox-MPK@MDL and its ability to actively target tumor cells. (B) Representative imaging of main organs in vivo of each group after injecting for 4 h. (C) Photograph of lung tissues collected from each group after 14 d treatment. Metastatic nodules in each lung tissue are indicated by yellow circles [95].

Fig. 8

(A) Schematic representation of using MΦ-NPs to neutralize endotoxins and proinflammation cytokines as a two-step process for sepsis management. (B) Levels of proinflammation cytokines, including TNF-α, and IL-6 in plasma. (C) Schematic of Fe₃O₄@MMs and their mechanism of neutralizing LPS. (D) Survival rates of endotoxic mice over 5 d following intravenous injection of PMX-B and Fe₃O₄@MMs immediately (left) and 0.5 h after (right) LPS injection [98,103].

Fig. 9

(A) Schematic representation of Neu-LPs designed to target the injured tissue and bind the inflammation cytokines. (B) Concentration profiles of inflammatory cytokines (TNF-α, IL-1β and IL-6) and chemokine (CXCL2) in ischemic hearts at various time points (1, 3, and 7 days) following injection of Neu-LPs. (C) Schematic representation of neutrophil-NPs designed to inhibit synovial inflammation and ameliorate joint destruction in inflammatory arthritis. (D) The study protocol of a therapeutic regimen with a CIA mouse model (left) and change of hind knee diameter on day 60 after CIA induction compared to that on day 0 (right). (E) The study protocol of a therapeutic regimen with a human TNF-α transgenic mouse model of inflammatory arthritis (left) and change of hind knee diameter on day 70 compared to that on day 0 (right) [99,110].

Fig. 10

(A) Schematic representation of TNPs designed for attenuating HIV infectivity. (B) TNP neutralization against bystander T cell killing induced by gp120_IIIB (left) and gp120_BaL (right). (C) Schematic illustration of macrophage biomimetic NCs-based drug delivery system (PLGA-LPV@M) for anti-inflammation and targeted antiviral treatment in COVID-19. (D) NETosis in neutrophils induced by COVID-19 patient serums was quantified using DNA dye Pico Green after treatment with PLGA@M in different concentrations. (E) The virus mRNA level in MHV-infected L929 cells after being treated with PLGA-LPV NPs and PLGA-LPV@M at different LPV concentrations [3,101].

Fig. 11

(A) Immune-modulating mechanisms for the management of AIDs via multi-target interruption of the self-amplified inflammatory response. (B) Preparation of PRM NDs from IFN-γ-treated RAW 264.7 cell membrane. (C) The process of how PRM NDs interact with CD4⁺ T cells to restore immune tolerance. (D) Representative flow cytometric histogram of CFSE-labeled T cells incubated with PBS, RM NDs, or PRM NDs. (E) H&E staining images from left posterior knee section. H stands for synovial hyperplasia and I for immune cell infiltration [130].

Fig. 12

(A) Immunomodulatory effects of MM functionalized PCL nanofibers. (B) Immunofluorescence images showed macrophages neighboring to or within (i) PCL, (ii) M0-PCL, (iii) M1-PCL, and (iv) M2-PCL nanofibers 7 days after subcutaneous implantation (Red: CD206 pro-healing macrophage; green: CD86 pro-inflammatory macrophage; blue: Hoechst staining nuclei) [134].

Fig. 13

(A) Schematic diagram of multi-antigen nanotoxin against Gram-negative bacterial infection. (B) The proportion of immunoglobulin A-producing B cells in superficial cervical lymph nodes after 21 days of nasal administration with blank solution, MΦ-NPs, or MΦ-toxoids. (C) Absorbance diagram of anti-PAS secreted IgG (left) and Ig A (right) levels in BAL fluid of mice on day 21 after nasal inoculation with a blank solution or MΦ toxoid by ELISA [139].

Fig. 14

(A) Schematic illustration of immune stimulation process by MANPs and mechanism in cancer prevention and treatment. (B) Tumor volumes in different groups. (C) Schematic illustration of the synthesis process of DCM/HCtSA/OVA micelle and its role in anti-tumor applications. (D) Representative fluorescent images of lymph nodes. (E) Tumor inhibition rates in different groups [119,140].