A summary of the advancements in strategies for the cell surface modification with synthetic molecules in this review.
| Strategy | Cell typea | Synthetic molecules modified on the cell surface | |
|---|---|---|---|
| Chemical covalent modification strategies | Amine groups (–NH2) | HUVECs | PEG,21 biotin–streptavidin22 |
| C2C12 cells | Poly(methacryloyloxy)ethyltrimethylammonium chloride (PMETAC)22 | ||
| MSCs | Heterodimerizing leucine,23 chitosan nanoparticles,24 sialyl Lewis X29 | ||
| RBCs | Biotin–streptavidin,26 PEG30,31 | ||
| T cells | Nanoparticles32 | ||
| Jurkat and NK cells | Biotin–streptavidin27 | ||
| Thiol groups (–SH) | RBCs | Nanoparticles36 | |
| DCs | Bovine serum albumin (BSA) protein shells41 | ||
| B16 cells | BSA protein shells41,43 | ||
| T cells | Nanoparticles33,34,38,39 | ||
| Vicinal diol groups | L929 cells | Fluorescent polymer44 | |
| MCF-7, HepG2 and HeLa cells | Pyrene derivative37 | ||
| B16 cells | Gadolinium DO3A amide48 | ||
| HDFs | DEGMA or NVP polymers49 | ||
| HepG2 cells | BSA nanoparticles50 | ||
| B16, AB22 and ZL34 cells | Contrast agents (Gd- and 68Ga-DOTA-EN)52 | ||
| PC-3, DU145 and Jurkat cells | Sialic acid-imprinted fluorescent core–shell SiO2 particles53 | ||
| MCF-7, HeLa and PC-3 cells | Polymer nanoparticles54 | ||
| RBCs | Supramolecular polymers58 | ||
| Carboxyl groups | MCF-7 cells | Reactive probe59 | |
| Convert diols into aldehydes | HDFs | Biotin–streptavidin60 | |
| HT29 and MDA-MB-231 cells | Maltol hydrazide61 | ||
| HepG2 cells | Dendrimer hydrazides62 | ||
| PEI conjugated with multiple hydrazide groups63 | |||
| MCF-7 cells | Peptide and protein64 | ||
| HeLa cells | p-Benzoquinone/ethylenediamine polymer65 | ||
| Convert disulfide bonds (S–S) to thiol groups | Human iPSC-derived-MSCs | ECM coating66 | |
| HepG2 cells | DNA bridge complex-templated silver nanoclusters (DNA bridge-AgNCs)67 | ||
| HeLa cells | Fluorescent dye, polymer, and nanoparticles69 | ||
| NEs | Liposomal stimulator of interferon genes (STING) agonists70 | ||
| Physical modification strategies | Hydrophobic insertion | HUVECs and HSFs | PEG21 |
| T cells | Tetrazine73 | ||
| DCs and PC-3 cells | Cucurbit[7]uril-based supramolecular polymer74 | ||
| CCRF-CEM cells, splenocytes, melanoma, human MSCs and beta cells | Synthetic peptide76 | ||
| RAW264.7 cells and L-O2 cells | β-Cyclodextrin (β-CD) and adamantane (ADA)77 | ||
| Hydrophobic insertion | Human T cells and B cells, erythrocytes, hepatocytes, L929 and HEK293T cells | Cell-penetrating peptide79 | |
| Hydrophobic insertion | MCF7, A549, LUDLU-1 cells | Aptamer80 | |
| HeLa cells | DNAzyme,82 DNA,89 multicomponent polymer,91 aptamer,80 core–shell upconversion nanoparticles92 | ||
| MCF-7 cells | Fluorescein isothiocyanate (FITC),83 core–shell upconversion nanoparticles92 | ||
| SubT1 cells | Biotin–PEG84 | ||
| MDA-MB-231 cells | Nitrilotriacetic acid (NTA)85 | ||
| NK cells,81 Jurkat, NK, and Ramos cells,86 CCRF-CEM cells,87 U937 cells,88 RBCs,107 lymphocytes106 | DNA | ||
| MSCs | Hyperbranched polyglycerol (HPG) covalently modified with vasculature binding peptides (VBPs)93 | ||
| Th9 cells, 4T1 cells | Peptides94,95 | ||
| Jurkat cells | ssDNA97 | ||
| 3T3 cells | Poly(oxanorbornene) block copolymers,98 PEG104 | ||
| HepG2 cells | Peptides,99 PEG100 | ||
| RIN cells | PEG101 | ||
| Fibroblast cells | Ketone and oxyamine,110,116,118 dialdehyde,112 hydroquinone117 | ||
| NK cells | Lewis X trisaccharide119 | ||
| T cells | 2,2,6,6-Tetramethylpiperidine groups120 | ||
| HeLa cells | DNA108 | ||
| Electrostatic interaction | HUVEC | Poly-l-lysine (PLL)21 | |
| Jurkat cells | TiO2 coating122 | ||
| hASCs | Chitosan derivative124 | ||
| HeLa, 3T3, and Jurkat cells | Poly(ethyleneimine) (PEI)126 | ||
| T cells | PLA nanoparticles125 | ||
| Layer-by-layer (LBL) self-assembly | HeLa cells | Cationic gelatin and anionic gelatin129,135 | |
| MSCs | PLL, hyaluronic acid (HA), and arginine-glycine-aspartic acid (RGD),128 gelatin,135 silk fibroin polyelectrolyte139 | ||
| RBCs | Chitosan-graft-phosphorylcholine, HA and PLL-PEG136 | ||
| DPCs | Gelatin and alginate137 | ||
| MIN6 cells | Gelatin and fibronectin (FN)138 | ||
| L929 cells | Silk fibroin polyelectrolyte139 | ||
| AML-12 cells and PBMCs | PLL and HA140 | ||
| T cells | Chitosan and alginate147 | ||
| iPSCs | FN, heparin (Hep), and chondroitin sulfate (CS)148 | ||
| Bioorthogonal strategies | Metabolic glycan labeling strategy | Jurkat cells | Probes,151 lipid nanoparticles,162 polymer–antibody conjugates156 |
| HEK 293T cells | Probes154 | ||
| MCF-7 cells | β-CD and aptamer155 | ||
| Metabolic glycan labeling strategy | A549 cells | Poly(hydroxyethyl acrylamide),157 polycation,158 poly(hydroxyethyl acrylamide) (pHEA)159 | |
| MCF-7 cells | Polycation158 | ||
| MSCs | Antioxidant liposome160 | ||
| Macrophages | Polyvalent spherical aptamer161 | ||
| DCs | Antigens, adjuvants and cytokines163 | ||
| 4T1 cells | Chlorin 6 (ref. 164) | ||
| HeLa cells | Probes183 | ||
| Halo-Tag protein | B16 cells,175 DCs,176 Hela cells172 | Glycopolymers | |
| Enzyme-mediated strategy | B cells | Biotin177 | |
| NK cells | Bio-macromolecules,174 Sialyl Lewis X and CD22-specific ligands185 | ||
| T cells | Bio-macromolecules174 | ||
| Mouse lung endothelial cells | Synthetic ligands and biotin178 | ||
| CHO cells | Probes,181 bio-macromolecules174 | ||
| RBCs | Probes,182 peptide173 | ||
| HEK 293T cells | Probes181 | ||
| HeLa cells | Probes183 |
Abbreviation for the full cell name or cell species: HUVECs: human umbilical vein endothelial cells; C2C12 cells: murine myoblasts; MSCs: mesenchymal stem cells; RBCs: red blood cells; Jurkat cells: acute T-cell leukemia cells; NK cells: natural killer cells; DCs: dendritic cells; B16 cells: murine melanoma cells; L929 cells: mouse fibroblast cells; MCF-7 cells: human breast adenocarcinoma cells; HepG2 cells: human liver cancer cells; HeLa cells: human cervical cancer cells; HDFs: human dermal fibroblasts; AB22 cells: mouse mesothelioma cells; ZL34 cells: human mesothelioma cells; PC-3 and DU145 cells: human prostate cancer cells; iPSCs: induced pluripotent stem cells; HT-29: human colon cancer cells; MDA-MB-231 cells: human breast cancer cells; NEs: neutrophils; HSFs: human skin fibroblasts; CCRF-CEM cells: human acute lymphoblastic leukemia cells; RAW 264.7 cells: mouse leukemia cells of monocyte macrophages; L-O2 cells: human normal liver cells; HEK293T cells: human embryonic kidney cells; A549 cell: human lung cancer cells; LUDLU-1 cells: human Caucasian lung squamous carcinoma cells; SubT1 cells: human CD4 expressing T-lymphoblastoid cells; U937: histiocytic lymphoma cells; Th9 cells: helper T cell 9; 4T1 cells: mouse breast cancer cells; 3T3 cells: mouse embryonic fibroblasts; RIN cells: mouse insulinoma cells; hASCs: human adipose-derived mesenchymal stem cells; DPCs: dermal papilla cells; MIN6 cells: pancreatic β-cells; AML-12 cells: human lung cancer cells; PBMCs: peripheral blood mononuclear cells; CHO cells: Chinese hamster ovary cells.