From: Nanobody: a promising toolkit for molecular imaging and disease therapy
Function and target | Combined with | Advantages | Disadvantages | Solution | References |
---|---|---|---|---|---|
Antagonist: EGFR, CXCR4, P2X7, HGF | Â - | (i) Small size (ii) High solubility and stability (iii) Excellent tissue penetration (iv) Recognizing new targets (v) Using together with mAbs | (i) Fast blood clearance (ii) High renal uptake (iii) Lack of Fc (iv) Immunogenicity | (i) Constructing multivalent nanobody (ii) Co-injecting with cationic amino acids (iii) Conjugating with an anti-albumin unit (iv) Linking with effector domains | |
Nanobody-based radionuclide: HER2 | 225Ac,131I, 177Lu | (i) Fast blood clearance (ii) Suited for conjugation | (i) High renal uptake (ii) Radiation toxicity to healthy cells | (i) Constructing multivalent nanobody, co-injecting with cationic amino acids, conjugating with an anti-albumin unit (ii) Linking with residualizing prosthetic group such as SGMIB (iii) Selecting high-affinity and high-internalization nanobody | |
Nanobody-mediated drug delivery system:  EGFR, HER2 | (i) Pharmeceutic carriers (ii) Chemotherapeutic drugs | (i) Can act as antagonist itself (ii) High specificity  (iii) Suited for conjugation | (i) Fast blood clearance (ii) The drug can damage normal cells | (i) Encapsulation in carriers, (ii) PEGylation | |
Nanobody-based immunotoxin: EGFR, CD7 | (i) Plant toxins (ii) Bacterial protein toxins such as PE and DT | (i) Lethal to cells in all phases (ii) High efficacy | (i) Immunogenicity (ii) Lysosome-sensitive sites in toxin part | (i) Linking nanobody with humanized nanobody scaffold (ii) Deleting lysosome-sensitive sites | |
Nanobody-peptide fusions: EGFR, DR, CEA | (i) The ligand of death receptor (TRAIL) (ii) Fc domains (iii) Cytokine | (i) Inducing ADCC and CDC (ii) Specifically recruiting effector cells to lesions | Fast blood clearance | (i) Constructing multivalent or nanobody, (ii) Glycosylation modification (iii) Crucial amino acid mutation in FR2 |