Table 4.
Examples of studies of PLGA particles targeted to DCs.
| Receptor | Formulation | Antigen / adjuvant | In vitro /in vivo | Administration route | Response compared to untargeted particles | References |
|---|---|---|---|---|---|---|
| Integrin, lectin and mannose receptors | PLGA MPs (˜2.5 μm) c.c. to RGD peptide; WGA; mannose-PEG3-NH2 | – | In vitro | n/a | ↑ uptake of targeted MPs | 108 |
| Integrin receptor | PLGA NPs (˜200 nm) c.c. to RGD peptide | OVA | In vitro and and in vivo | Oral | ↑uptake by M cells and ↑ IgG responses in vivo | 107 |
| PLGA MPs (˜1 μm) containing alginate or c.c. RGD-alginate | SPf66; S3 | In vivo | i.d. | ↑ Ab and cellular responses and more balanced Th1/Th2 responses; ↑ IFN-γ secretion and splenocyte proliferation | 109 | |
| Mannose receptor | Mannan c.c. to PLGA NPs (˜400 nm) | OVA | In vitro and and in vivo | s.c. | ↑ antigen-specific CD4+ and CD8+ T cell responses in vitro and and vivo | 113 |
| Mannan-coated on or c.c. to PLGA NPs (˜400-500 nm) | – | In vitro | n/a | ↑ DC uptake and cell surface markers (CD40, CD86) and secretion of inflammatory cytokines (IL-12, IL-6 and TNF-α) | 111,114 | |
| DC-SIGN | PLGA MPs (2 μm) and NPs (200 nm) c.c. to humanized hD1 anti-DC-SIGN antibody | BSA; TT | In vitro | n/a | MPs were taken up nonspecifically; NPs effectively targeted DCs: ↑ uptake & Ag-specific T cell responses at 10–100 fold lower concentrations | 12 |
| DEC-205 | PLGA NPs (˜200 nm) c.c. to bfFp containing anti-DEC-205 antibody fragment | OVA | In vitro and and in vivo | s.c. | 2-fold ↑ receptor-mediated uptake of bfFp functionalized NPs in vitro; ↑ OVA-specific IgG responses in vivo | 117 |
| DEC-205 | PLGA NPs (˜200-250) c.c. to anti-DEC-205 mAb | OVA / KRN | In vitro and and in vivo | Footpads | ↑ antigen-specific humoral & CTL responses and promoted potent antitumor responses | 119 |
| DEC-205; CD40; CD11 | PLGA NPs (200 nm) c.c. either with anti-DEC-205, -αCD40 or -CD11 mAbs | OVA / poly(I:C) & R848 | In vitro and and in vivo | s.c. | ↑ uptake of targeted NPs & IL-12 production and expression of IFN-γ in vitro; ↑ OVA-specific CD8+ T cell responses in vivo | 11 |
| CD40 | PLGA NPs (200 nm) c.c. with anti-αCD40 mAb | OVA; HPV-E7 / poly(I:C) & Pam3CSK4 | In vitro and and in vivo | ↑ selective delivery to DCs and ↑ CD8+ T cell priming in vitro; ↑ tumor control and prolonged survival of tumor-bearing mice in vivo | 14 |
Ab: antibody; Ag: antigen; <: less/lower than; >: more/higher than; <<: much less/lower than; >>: much more/higher than; ≥: equal or higher than; ˜: similar; ↑: increased/high: ↓: decreased/low; CFA: complete Freund's adjuvant; sX: soluble X; c.c.: chemically conjugated; bfFp: bifunctional fusion protein of strepatividin