Table 2C.
Summary of the different strategies followed in order to facilitate the endosomal escape of antigens in dendritic cells
| Mechanism | Critical feature | Nanosystem | Key results | Ref. |
|---|---|---|---|---|
| Membrane disruption | pH-responsive diblock copolymers | Polyacrylic micelles | pH-responsive micelles caused a higher increase of CD8+ T cell responses in vitro and in vivo than non-pH-responsive controls | [117] |
| Fusion with the membrane | pH-sensitive poly(glycidol) polymers | EPC/DOPE/polymer liposomes | Modified liposomes elicit stronger cellular responses than unmodified systems in vivo | [119] |
| Unknown | Positive lipids (DOTAP or DC-Chol) | DOTAP/Chol/DSPE-mPEG, DC-Chol/DOPE/DSPE-mPEG, EPC/Chol/DSPE-mPEG liposomes | Liposomes with cationic lipids, but not with anionic ones, increased cross-presentation and CD8+ T cell activation in vitro | [120] |
| Membrane disruption (?) | Disulfide crosslinking of the gel | Bioreducible alginate/PEI nanogels | Humoral and cellular responses where enhanced in vitro by the bioreducible nanogel in comparison to the non-reducible one | [121] |
| Unknown | Disulfide bond to nanocarrier | Propylene sulfide NPs | More efficient cross-presentation of the antigen when attached by a reducible link rather than by a non-reducible one | [122] |
| Unknown | ISCOMATRIX adjuvant | ISCOMATRIX + antigen (OVA or E. coli protein) | ISCOMATRIX adjuvant allowed a rapid translocation of the antigen from lysosomes to the cytosol and a greater cross-presentation in vitro, in comparison to immune complexes | [123] |
| Activation of endosomal TLR3 or TLR9 | Poly(I:C), CpG or plasmid DNA | Liposome-Ag-nucleic acid complexes | Complexation of TLR agonists showed an increased CD8+ T cell activation independent of CD4+ T cell help, in comparison to liposomes without TLRs. Also, both prophylactic and therapeutic effects were achieved in two different mice models | [125] |
| Activation of endosomal TLR3 | Poly(I:C) | Cationic adjuvant system (CAF01), composed of DDA and TDB | Immunization with OVA + DDA/TDB/poly(I:C) elicited stronger and longer CD8+ T cell responses in mice than CAF01 alone. In addition, less inflammatory side effects were observed than when administering poly(I:C) alone | [126] |
| Activation of endosomal TLR7/8 | Resiquimod | Temperature-responsive self-assembling particles, based on resiquimod anchored to HPMA or NIPAM scaffolds | Particle formation was key to diminish systemic toxicity and to generate Th1 bias responses, high antibody titers and CD8+ T cell activation in vivo | [127] |
Ag: antigen; CSF21: cationic adjuvant system; Chol: cholesterol; DC-Chol: 3β-[N-(N′,N′-dimethylaminoethane)- carbamoyl] cholesterol; DDA: dimethyldioctadecylammonium; DOPE: 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine; DOTAP:, 2-dioleoyl-3-trimethylammonium-propane; DSPE-mPEG: 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000]; EPC: egg phosphatylcholine; HPMA: hydrophilic N-(2-hydroxypropyl) methacrylamide; NIPAM: N-isopropylacrylamide; NP: nanoparticle; OVA: ovalbumin; PEI: polyethylenimine; poly(I:C): polyinosinic–polycytidylic acid; TDB: trehalose 6,6′-dibehenate; Th1: T helper 1; TLR: toll-like receptor