Table 3.
Globular protein-based delivery systems for nucleic acids.
| Material | Cargo | Cell line/Model | In vitro Efficacy | RoA | In vivo Efficacy | Ref |
|---|---|---|---|---|---|---|
| Albumin | ||||||
| PDMA-BSA | eGFP, luciferase pDNA | HEK293T, NIH/3T3, D1 (murine bone marrow cells) | Efficacy comparable to PEI at optimized BSA:DNA mass ratios | N/A | N/A | 196 |
| Ethylenediamine-functionalized BSA | siBcl2 | B16 (IV administered B16 cells for lung metastasis model in C57BL/6) | ~50% target knockdown in optimized conditions, comparable to Lipofectamine | IV | Particle accumulation in mouse lungs related to particle size (D ~5 μM). cBSA+siBcl2 particles enabled significant reduction in # of lung metastases vs controls | 197 |
| PEI-HSA | eGFP, luciferase pDNA | A549 | PEI-HSA nanoparticles performed comparably to Lipofectamine with less cytotoxicity | N/A | N/A | 198 |
| PEI-HSA | Luciferase pDNA | Mouse cerebellar granule cells | ~80% of treated wells showed luminescence following transfection | N/A | N/A | 199 |
| bPEI-HSA | siTurboGFP | HPMEC, MDA-MB-231 | ~90% knockdown in both cell types, comparable to Lipofectamine | N/A | N/A | 200 |
| PEI-BSA | Cas9 pDNA | MDA-MB-231 | Nanoparticles enabled efficient uptake of pDNA; editing efficiency not evaluated | N/A | N/A | 201 |
| BSA | siKRAS (G12S) | A549 | Significant target knockdown resulting in reduced cell viability | N/A | N/A | 202 |
| MSA (in situ) | Maleimide-anti-miRNA-21 ASO | U87 | Significant changes in miRNA-21 target gene expression | IV | In situ binding to endogenous circulating albumin resulted in prolonged circulating half life, increased tumor accumulation, and ~50% slowing in tumor growth | 203 |
| Heat shock proteins | ||||||
| HSP-Tat-RGD RGD: integrin targeting | siTERT | CT26 (murine colorectal carcinoma cells/xenograft in BALB/c nude mice) | RGD addition significantly reduced TERT expression; apoptosis rate ~1.5-fold higher than that of the Lipofectamine/si TERT control. | IV | Intravenous injection of HSP-Tat-RGD/siTERT (d 0, 2, 4, 6, 8) resulted in markedly reduced tumor volume (evaluated d 20) | 204 |
| Ferritin | ||||||
| Human heavy chain apoferritin | siInsR | Caco-2, Human PBMCs | Enabled ~85% knockdown of insulin receptor in Caco-2 cells, ~50% knockdown in activated human PBMCs | N/A | N/A | 205 |
| Pas-HumAfFT (humanized archaea ferritin); HumAfFT point mutation (M54C); PA (cationic polyamine) | siGAPDH | HeLa, HepG2 (human hepatoma), MCF-7(human breast cancer) | > 20% GAPDH silencing observed in HeLa, HepG, and MCF-7 cells. | N/A | N/A | 206 |
| Humanized A. flugidus ferritin | miRNA-145–5p | NB4 (human acute promyelocytic leukemia) | Granulocytic differentiation observed in cell morphology analysis, although not sufficient to achieve full differentiation | N/A | N/A | 207 |
| Poly(L-lysine) modified heavy chain apoferritin (4L-HFn) | siEGFR | HeLa, 4T1 (murine breast cancer cells/tumor model in female BALB/c mice) | Successfully downregulation of EGFR protein (>70%), but not as effective as Lipofectamine. | IV | Significant accumulation of 4L-HFn@siRNA in tumors from 2 to 10 h; tumor growth suppression effect following treatment every 2 d for 10 d | 208 |
ASO, antisense oligonucleotide; bPEI, branched poly(ethylenimine); BSA, bovine serum albumin; HPMEC, human pulmonary microvascular endothelial cells; HSP, heat shock protein; HSA, human serum albumin; lnsR, insulin receptor; MSA, Mouse serum albumin; PAMAM, polyamidoamine; PDMA, poly(N,N-dimethylacrylamide); PEI, poly(ethylenimine).