Cell Membrane-Coated Nanoparticles for Dental, Oral, and Craniofacial Diseases

Abstract

Dental, oral, and craniofacial diseases can substantially impact the quality of human life, thereby posing a serious public health concern. Although conventional therapies such as surgery have solved these problems largely, the prognosis of patients is not always satisfactory. Cell membrane-coated nanoparticles (CMCNPs) carry nanodrugs with the help of natural cell membranes, therefore utilizing their remarkable ability to interface and interact with their surrounding environment. These nanoparticles have demonstrated substantial advantages in drug targeting, prolonging blood circulation time, penetrating biofilms, and immune escape. With the assistance of CMCNPs, the therapeutic effects of dental, oral, and craniofacial diseases can reach a higher level. CMCNPs have been applied for dental, oral, and craniofacial diseases for various conditions such as head and neck cancer, periodontal disease, and oral biosignal detection. For the therapies of head and neck cancer, CMCNPs have been widely utilized as a tool of chemotherapy, phototherapy, and immunotherapy, while yet to be exploited in imaging technique. In the end, we summarized the challenges and prospectives of CMCNPs for dental, oral, and craniofacial diseases: large-scale production with uniform standards and high quantity, extensive application directions in dental, oral, and craniofacial regions (implant, endodontics), and the promotion of its clinical application.

Fig. 1.

The importance of CMCNPs applied in dental, oral, and craniofacial region. The advantages of CMCNPs for dental, oral, and craniofacial diseases include bacteria, neuropathic pain, and tumor inhibition.

Fig. 2.

The fabrication of CMCNPs. (A) Acquisition of cell membrane vesicles from cell culture. (B) Manufacture techniques of NPs. (C) Fusion techniques of vesicles and NPs. AFM, atomic force microscopy; DLS, dynamic light scattering; LC-MS, liquid chromatography–mass spectrometry; TEM, transmission electron microscopy; XRD, x-ray diffraction.

Fig. 3.

Applications of CMCNPs for dental, oral, and craniofacial regions. (A) CMCNP function process of chemotherapy, phototherapy, and immunotherapy for HNC treatment. (B) Application of a biomimetic NP manufactured from functioned cell membranes and NPs loaded with antibiotics with targeted antimicrobial and precise immune regulation through topical administration of periodontitis. (C) Other applications of CMCNPs for dental, oral, and craniofacial diseases (e.g., exosome detection and drug delivery). CMCNPs, cell membrane-coated NPs; GinPa-MSCs, gingival papilla mesenchymal stem cells; LPS, lipopolysaccharide; PTX, paclitaxel.

Fig. 4.

CMCNPs for chemotherapy in the treatment of HNCs. (A) Pt nanodelivery system mediated by PDTC [68]. (B) DPSC membrane modified with MOFs for DOX delivery [97]. (C) Nanoscale cobalt–ferrocene metal–organic framework incorporated with oral CCM for autophagy inhibitor HCQ delivery [69]. CM, cell membranes; Co–Fc, cobalt–ferrocene metal–organic framework; CXCL8, cryo-electron microscopy structures of IL-8; CXCR2, CXC chemokine receptor 2; DOX, doxorubicin; DPSC, dental pulp mesenchymal stem cell; GNPs, gelatin NPs; HCQ, hydroxychloroquine; MOFs, metal–organic framework NPs; OSCC, oral squamous cell carcinoma; PDTC, patient-derived tumor cell; PDX, patient-derived xenograft; Pt, cisplatin; ROS, reactive oxygen species.

Fig. 5.

CMCNPs for phototherapy in the treatment of HNCs. (A) CCM-coated AuNRs for PTT and radiotherapy on OSCC [106]. (B) Biomimetic phototherapeutic nanoagent based on bacterial double-layered membrane vesicles for OSCC treatment [111]. (C) PLT-facilitated PTT of HNSCC [114]. (D) Cancer stem cell–PLT hybrid membrane-coated magnetic NPs for enhanced PTT of head and neck squamous cell carcinoma (HNSCC) [53]. [CSC-P]MN, CSC-PLT membrane-coated Fe₃O₄ NP; AuNRs, gold nanorods; CSC, cancer stem cell; DC, dendritic cell; DMVs, double-layered membrane vesicles; GNR, gold nanorod; GNR@Mem, CCM-coated gold nanorods; IR780, a near-infrared dye possessing both PDT and PTT capabilities; LPS, lipopolysaccharide; MN, iron oxide NP; MRI, magnetic resonance imaging; OSCC, oral squamous cell carcinoma; PBAE, poly(β-amino) ester; PEG, polyethylene glycol; Pg, Porphyromonas gingivalis; PLT, platelet; PTT, photothermal therapy.

Fig. 6.

CMCNPs for immunotherapy in the treatment of HNCs. (A) Hybrid nanovaccine formed from TEX and CCR7 retained DCMV for HNSCC treatment [33]. (B) Biomimetic nanoplatform integrating plasma membrane components of leukocytes and tumor cells for remarkably enhanced solid tumor homing [54]. CCL21, CC-motif chemokine ligand 21; CCR7, CC-chemokine receptor 7; CTL, cytotoxic T lymphocyte; DC, dendritic cell; DCMV, dendritic cell membrane vesicle; Hy-M-Exo, a hybrid nanovaccine; IFN-γ, interferon-γ; MPLA, monophosphoryl lipid A; TEX, tumor-derived exosome; TNF-α, tumor necrosis factor-α.

Fig.  7.

CMCNP treatments of periodontitis. (A) Macrophage membrane-coated nanodrug delivery system targeting Pg [131]. (B) Penetrating macrophage-based nanoformulation-encapsulating hydrogel targeting Pg [132]. (C) S. gordonii membrane-coated H₂O₂ self-supplied nanocomposite for S. gordonii inhibition [134]. (D) Cell membrane vesicles with enriched CXCR4 targeting inflammatory sites [138]. (E) Polydopamine NP based on gingival fibroblast membrane [65]. (F) Nanoparticulate regulatory T cells for inhibiting inflammatory reaction of periodontitis [64]. (G) 3D-printed bioink loading with stem cells and cellular vesicles for periodontitis-derived bone defect repair [63]. ALP, alkaline phosphatase; ApoE^−/−, apolipoprotein E knockout; ATP, adenosine triphosphate; C5a, component 5a; C5aR, C5a receptor; CD, cluster of differentiation; CMVs, cell membrane vesicles; CTLA-4, cytotoxic T lymphocyte-associated protein-4; Cur, curcumin; CXCR4, CXC chemokine receptor 4; EPL, ε-poly-l-lysine; EPLGMA, GMA-modified EPL; GMA, glycidyl methacrylate; hPDLSCs, human periodontal ligament stem cells; IL, interleukin; LAG3, lymphocyte-activation gene 3; LPS, lipopolysaccharide; MDSCs, myeloid-derived suppressive cells; Me, metronidazole; MHC II, major histocompatibility complex class II; MZ@PNM, metronidazole @ penetrating nanomacrophage; OCN, osteocalcin; PDLC, periodontal ligament cell; PDLSC, periodontal ligament stem cell; Pg, Porphyromonas gingivalis; ROS, reactive oxygen species; RUNX2, runt-related transcription factor 2; SDF-1, stromal cell-derived factor-1; ST, simvastatin; TLR, Toll-like receptor; TNF-α, tumor necrosis factor-α; ZnO₂/Fe₃O₄@MV NPs, S. gordonii membrane-coated ZnO₂ NPs shell assembled with Fe₃O₄ NPs.

Fig. 8.

Future application directions for CMCNPs. CMCNPs for dental, oral, and craniofacial diseases should improve in 3 aspects: standardized and efficient production, expansion applying regions (e.g., endodontics and implant dentistry), and new techniques for early diagnosis, low pieces, and large-scale clinical trials for the guarantee of clinical application.