Table 1.

Overview of application-specific studies reporting uptake of DNA nanostructure by mammalian cell and animal models

Application	DNA nanostructure (size nm/mass kDa)	Cell type primary/transformed	Targeting moiety on DNA/drug or Protein	Dosage (in ×104 cells)a	Tracked end-point	Cytotoxicityb	Ref. (year)
Immune-stimulation:	Rectangle reconfigured as tube (90 nm)	BMDC, mice	OVA, gp100, and Adpgk peptides	2 nM in 3×	Endosome		98 (2021)
	Octahedron (50 nm), tube (400 nm/4 MDa), nanorod (89 nm/4 MDa)	3T3, HEK-293, H441	None	1 nM in 1×	—	None >7 d	79 (2014)
	Disk (80 nm/4 MDa)	RAW264.7	CpG	10–1000 nM in 2×	Endosome	None >5 h	21 (2022)
	Tetrahedron (7 nm/82 kDa)	RAW264.7	CpG	100 nM in 50×	—	None >24 h	99 (2011)
	Rectangle (90 nm/4 MDa)	RAW264.7, THP-1	IgG	1 μM DNA in 3×	—	—	50 (2021)
	Tube (80 nm/4 MDa)	Splenic macrophages	CpG, CpG PTO, CpG chimera	2.4 nM 50 μL DNA in 40×	Lysosomes	None >18 h	72 (2011)
	Tetrahedron (7 nm/82 kDa)	RAW 264.7, primary dendritic cells	CpG, streptavidin	62.5 nM in 2.5×-25×	Lysosomes	—	53 (2012)
Nucleic acid delivery:	Tetrahedron (7 nm/82 kDa)	HeLa	siRNA	10–80 nM in 15×	—	None >24 h	31 (2012)
	Tube (27 nm/140 kDa)	HeLa	None	10 nM	Endosome	None >24 h	100 (2014)
	Rectangular prism (10 nm/160 kDa)	HeLa	DNA trigger strand	75 nM in 1×	—	None >72 h	26 (2016)
	Cube (7 nm/82 kDa)	HeLa, primary B-lymphocytes	DNA trigger strand	250 pmole in 10×	—	—	101 (2014)
	Rectangle, tube (32 nm–64 nm)	DMS53, NSCLC	siRNA	16.7 nM in 1×	Cytoplasm	None >8 h	46 and 47 (2020)
	Tetrahedron (7 nm/82 kDa)	Mice	SARS-CoV-2 aptamer	500 nM 100 μL inj.	—	None >12 h	19 (2022)
	Tetrahedron (7 nm/82 kDa)	Mice	TGF-β1 mRNA	1 μM 200 μL inj.	Liver targeting	None >24 h	102 (2022)
	Tetrahedron (7 nm/82 kDa)	Mice	BACE1 aptamer	1 μM 100 μL inj.	Cross BBB	—	18 (2022)
Pharmaco-chemical/drug:	Triangle (120 nm), rod (400 nm)	MCF-7	None/DOX	50–100 μM	—	None >48 h	6 (2012)
	Disk (62 nm/4 MDa), donut (44 nm/4 MDa), sphere (62 nm/4 MDa)	MCF-7, MDA-MB-231	MUC1 aptamer/DOX	1 nM in 0.3×	—	None >48 h	5 (2022)
	Cross, rectangle, triangle (50 nm/4 MDa)	MDA-MB-231	None/DOX	1.25–5 nM in 0.3×	Lysosomes	—	8 (2018)
	T-nanotube, S-nanotube (100 nm/4 MDa)	MDA-MB-231, MDA-MB-468, and MCF-7	None/DOX	50–15 000 nM Dox in 20×	Endosomes	—	103 (2012)
	Tetrahedron (7 nm/82 kDa)	U87MG	Tumor penetrating peptide/DOX	50 nM in 0.4×	—	—	104 (2016)
	3D DNA NS (100 nm	MCF-7, mice	MUC1 aptamer	4 μM in 10×	—	—	105 (2022)
Protein delivery:	Rectangle reconfigured as a tube (90 nm/4 MDa)	HUVEC, mice	AS1411 aptamer/thrombin	—	—	None >72 h	9 (2018)
	Rectangle (90 nm/4 MDa)	MCF-7	MUC1 aptamer/RnaseA	1 nM	—	None >48 h	12 (2019)

Abbreviations: Adpgk = neoantigen peptide derived from MC-38 colon carcinoma, CpG = unmethylated cytosine–guanine dinucleotide motifs, DOX = doxorubicin, gp100 = peptide vaccine from melanoma antigen glycoprotein, MUC1 = mucin 1 protein overexpressed in malignant cells, OVA = ovalbumin peptide epitope presented by class I major histocompatibility complex, PTO = kinase substrate, siRNA = small interfering RNA, inj = tail vein injection, BBB = blood brain barrier. Cell types: BMDC = bone marrow derived dendritic cells; COS = monkey kidney fibroblast cells; DMS53 = human small cell lung cancer cells; H1299 = human non-small cell lung cancer cells; H441 = human distal lung epithelial cells; HEK293 = human embryonic epithelial kidney cells; HeLa = human cervical cancer cells; Huh7 = human epithelial cancer cells; HUVEC = human umbilical vein endothelial cells; MCF-7 = human breast cancer cells; MDA-MB = human epithelial breast cancer cells; NSCLC = human non-small cell lung cancer cells; NIH-3T3 = mouse embryonic fibroblast cells; RAW264.7 = mouse macrophage cells; THP-1 = human leukemia monocytic cells; U87MG = human glioblastoma.

^aDosage is given as ×10⁴ cells. For example, first entry represents 3 × 10⁴ cells.

^bCytotoxicity in the presence of bare DNA NS only (not the treatment in some cases).