. Author manuscript; available in PMC: 2019 Sep 26.

Published in final edited form as: Chem Rev. 2018 Jul 27;118(16):7409–7531. doi: 10.1021/acs.chemrev.7b00678

Table 6.

Cargo loaded versus membrane disruption approach. Techniques marked with red text represent accessible methods that are either commercially available or trivial to perform with common lab equipment.

MODALITY	METHOD	CARGO
		Nucleic Acids and their Analogues			Peptides / Proteins / Antibodies / RNPs etc.	Generic Macromole cules (e.g. Dextrans)	Small Molecule Drugs / Probes / Dyes / Sugars / Ions etc.	qDots / CNTs / Synthetic Nanomater ials etc.	Large Cargo: Bacteria, Organelles, Beads etc.
		vector DNA	mRNA	Oligos	Peptides / Proteins / Antibodies / RNPs etc.	Generic Macromole cules (e.g. Dextrans)	Small Molecule Drugs / Probes / Dyes / Sugars / Ions etc.	qDots / CNTs / Synthetic Nanomater ials etc.	Large Cargo: Bacteria, Organelles, Beads etc.
DIRECT PENETRATION
Mechanical	Micro-injection	pDNA^70–72, ⁵⁶⁵, viral DNA^70,564,1487	mRNA^109,1488	Antisense Oligonucleo tides^81,566, siRNA⁸⁵	Proteins ^162–166, ^562,1489, Antibodies¹⁴⁹⁰, Peptides^561, ¹⁴⁹¹, Cas9 protein / RNP²²⁴	Dextrans¹⁴⁹²	Dyes⁵⁵³, Mercury²⁹⁸, Trehalose¹⁴⁹³	qDots^{273,1494,1495}, MW-CNTs²⁹⁴, SW-CNTs²⁸³	Bacteria²⁹⁸, Nuclear transplant^300–302, Chromoso me transplant³⁰⁷, Sperm / IVF³⁰⁵,³⁰⁶, Mito-chondria³¹⁰, Artificial vesicles¹⁴⁹⁶ Beads^1497,1498, Silicon barcodes³³⁰
	Penetrating Projectiles (Biolistics)	pDNA^364,600	Cas9 mRNA¹⁴⁹⁹, mRNA^620–622	siRNA^623,624	Proteins^626–628, Cas9 protein / RNP⁶²⁹		Dyes^618,1500, Indicators⁶¹⁷	PEBBLE nano-sensors¹⁵⁰¹	Beads^325,327, Latex particles³²⁶
	Nanowires & Nano-needles	pDNA^185,363, ^{634,643,677,1502}		siRNA^185,638,639	Proteins^185,638, Peptides¹⁸⁵, Cre Recombina se⁶⁴⁰, Antibodies⁶⁴¹		Drugs¹⁸⁵, Molecular Beacons⁶⁴²	qDots⁶⁴³, DNA Nano-cages⁶⁴⁴
	Nanostraws	pDNA^664,666, ⁶⁷¹			Proteins⁶⁷¹	Dextrans^665, ⁶⁷¹	Dyes⁶⁶⁴,⁶⁶⁶, Co²⁺ ions³⁸⁷, Ca²⁺ ions⁶⁶⁷, Small molecule probes⁶⁶⁸	qDots⁶⁷⁰
PERMEABILIZATION
Mechanical (Solid Contact)	Cell Scraping	pDNA⁵⁰³		Antisense Morpholinos ^{721,1503–1505}	Proteins^176,501, ^709–715, Antibodies^716–718, Peptides^719,720	Dextrans^176, ⁷²², Lipopolysac charide⁷²³	Dyes^724–726
	Bead Loading	pDNA⁶⁹³			Proteins^699–701, Fab Fragments^703, ⁷⁰⁴, Antibodies^696–698, Peptides⁷⁰²	Dextrans^177, ^699,1506	Nucleotides ^695,919, RNA probes¹⁵⁰⁷, PNA probes⁷⁰⁵, SNAP-reactive dyes⁷⁰⁶	qDots⁷⁰⁸, SW-CNTs⁷⁰⁷
	Scratch Loading					Dextrans⁷²⁷	Dyes⁷²⁸	qDots⁷⁰⁸
	Microfluidic Cell Squeezing / Constrictio n-Mediated Disruption	pDNA^227,741, ^749,754,755	mRNA^184,749	siRNA^184, ^227, ^744,750,754, tRNA⁷⁴⁷	Proteins^184,744, ^745,749,1508, Cas9 RNPs^227,755	Dextrans^{184, 227,741,744,750}	Dyes^184,741,755, Tags¹⁵⁰⁸, Drugs¹⁵⁰⁹	qDots²⁸⁷, CNTs¹⁸⁴
	Nanowire Permeab-ilization	Lipid-pDNA complexes⁶⁵⁴, pDNA⁷⁶¹			Antibodies⁶⁵⁴	Dextrans⁷⁶¹	Dyes^678,683	qDots⁶⁵⁴	∼200 nm polystyrene beads⁶⁵⁴
	Sudden Cell Shape Changes / Protease Treatment			Oligonucleo tides⁷³².	Proteins^732,735, ^737,738, Peptides⁷³²	Dextrans^730, ^732,1510	Dyes⁷³³
Mechanical (Fluid Shear)	Syringe Loading / Microfluidic / Bulk Fluid Shear	pDNA^765,787		Antinsense morpholinos⁷⁶⁶	Proteins^770,774 ^{,776–780,783}, Antibodies ^{771–773,775,781}	Dextrans^178, ^{769,783,785,787}	Dyes⁷⁸⁶, Nucleotides ^767,768
	Sono-poration	pDNA^503,792, ^{793,795,801,816–822,} ¹⁵¹¹	mRNA⁸²⁶	siRNA^824,825, Antisense oligonucleo tides⁸²³, ssDNA¹⁵¹¹	Proteins^790,828, Antibodies⁸⁵², Peptides⁸⁵³	Dextrans^503, ^{789,790,812–814,} ^{827,828,830–836}	Dyes^764,808,813, ^{814,820,828,835,} ^{837–845,869}, Drugs^{835,846–850}	25–75 nm nanoparticl es⁸³¹	Viral particles⁸⁵¹
	Shock Wave-Mediated Permeabiliz ation	pDNA^{1264,1512–1514}		Antisense oligonucleo tides¹⁵¹⁵	Proteins⁸⁶⁴, Peptides⁸⁶⁷	Dextrans^860, ^862,863	Dyes^862,866,868, ^869,872, Drugs¹⁵¹⁶
	Laser-Induced Cavitation	pDNA^313,876, ^880,882,1517	mRNA³¹³	siRNA^884,886,887	Proteins^314,882, Antibodies¹²⁷²	Dextrans^876, ^{881,885,887,890,} ^{892,1518–1521}	Dyes^447,843,877, ^{881,882,885,889,} ^{891,892,1520,1522}	qDots^288,289,1521, Gold nanoparticl es¹⁵²³	Bacteria^313,314, Mitochondr ia³¹⁵, ∼200 nm polystyrene beads³¹³
Mechanical (Pressure)	Hypo-Osmotic Shock	pDNA⁹³⁸			Proteins^172,173, ^{913,927,929,937}, Peptides^914,924	Dextrans^925, ^937,1524	Dyes^914,1525, Lanthanideions/complexes^930–935, Nucleotides^914–923, Nucleosides⁹¹⁴, BAPTA⁹²⁸	qDots²⁹⁰, ∼5 nm gold nanoparticl es⁹²⁶
	Hydrostatic Pressure	pDNA^941,942, ^{944,947,952,953,} ^{961,966,967,1526–1528}, Bacterial artificial chromo-somes (BACs)⁹⁴⁶	mRNA⁹⁴⁷	ssODN^951,952, gRNA⁹⁵⁴, siRNA^944,945, ^960,1527, Antisense morpholinos¹⁵²⁹, Antisense oligonucleo tides^{959,961–965}	Proteins^943,1530, Antibodies¹⁵³⁰		Dyes^943,947		~100 nm Polystyrene microspher es⁹⁶⁸
	Osmotic Rupture of Endosomes			siRNA^1005,1006, Antisense oligonucleo tides¹⁰⁰¹, Antisense morpholinos⁷⁶⁶	Proteins^174,175, ^970–984, Antibodies^976, ^985–989, Peptides^992–994, Cell lysate⁹⁹⁵	Dextran^174, ^989–991, Hyaluronan^996,997	Trehalose⁹⁹⁸, Lanthanide imaging probes^260,261, Dyes^989,999, UDP-glucuronic acid¹⁰⁰⁰	qDots¹⁵³¹, Protein-conjugated qDots^{285,1003,1004}	Virus particles¹⁰⁰²
Electro-poration	Conventional Electroporation	pDNA^53,1066, ¹⁰⁶⁷	mRNA^25,54,56, ^{124,126–128,} ^{221,518,1064,} ^{1065,1211,1214,} ^{1219,1223,1225,1226,} ^{1238,1241,1242}	Antisense oligonucleotides¹⁰⁵⁸, siRNA^{104,1059–1063}	Proteins^180,210, ^{504,1045–1051}, Antibodies^181, ^{200,495,1052–1056}, Cas9 protein / RNP^156,218, ^{219,221,222,1057}	Dextrans^504, ^{1030,1080,1207}	Dyes^{180,1030–1033}, Radio-tracers¹⁰³⁵, SNAP-reactive dyes⁷⁰⁶, Sugars^{268,430,1036,1037}, Metabolites ^1034,1038, Drugs^{254,255,1039,1040}, Ions^1041,1042, Molecular Beacons^1043,1044	qDots^{273,291,292,1068}, 20nm gold nanoparticles¹⁰⁶⁹
	Microelectroportion	pDNA^1175,1177, ^{1178,1180,1181,} ^1183,1532		siRNA^1183,1532, miRNA¹¹⁸³	Proteins¹¹⁸³	Dextrans¹¹⁸²	Dyes^{449,1175,1179–1183}
	Nanoelectroporation	pDNA^666,1184, ¹¹⁸⁵		siRNA¹¹⁸⁴, Oligonucleo tides¹¹⁸⁴	Proteins¹¹⁹²	Dextrans^1192, ¹¹⁹³	Dyes^666,1184, Molecular Beacons^1184,1193	qDots¹¹⁸⁴
Thermal	Cooling-Heating Cycle						Trehalose^262,264,998
	Supraphysi ological Heating	pDNA^1265,1266			Proteins¹⁵³³		Dyes¹¹²⁷
	Laser Absorption Converted to Heat	pDNA^1275,1276		siRNA¹⁵³⁴	Antibodies¹²⁷³	Dextrans^1272, ¹²⁷⁶	Dyes^{1271,1272,1274–1276,1535}
Optoporation	Laser Optoporati on	pDNA^441,443, ^{444,1277,1279–1305}	mRNA^121,1300	siRNA^{1280,1290,1299}, Antisense morpholinos¹³⁰⁰	Peptides^446, ¹³⁰⁶, Proteins^1280, ¹²⁹⁰	Dextrans^{1280,1290,1296,1300,} ^1307,1308	Dyes^{121,440–444,} ^{446,1280,1287} ^{,1288,1290,1292,} ^{1293,1295,1301,} ^{1304,1308–1313}, Sucrose⁴⁴⁵, Molecular beacons¹³¹⁴, Ions^1280,1290, ¹³¹⁵	Semiconductor nanocrystals^1280,1290, Gold nanoparticles¹³¹⁶, qDots¹³¹⁷	~1 μm Polystyrene beads¹³¹⁸
Biochemical	Organic Solvents & Penetration Enhancers	pDNA¹³³⁰	mRNA¹³³⁰		Proteins¹³³⁰
	Detergents & Surfactant: Generic				Proteins¹³⁶⁶, Antibodies^179, ¹³⁶⁶		Nucleosides ¹³⁶⁵, Dyes¹³⁶⁵, Nutrients & Metabolites ¹³⁶⁵, Ferro-cyanide¹³³⁹
	Detergent: Saponin Family				Proteins⁴⁹⁷, Peptides⁴⁹⁷, Antibodies¹³⁶⁰, Cytoplasmic extracts¹³⁵⁸	Dextrans¹³⁵⁸	Inositol¹³⁵⁶	~20 nm nanoparticles¹³⁵⁹, qDots²⁹⁰
	Pore-Forming Toxins: CDC Family			siRNA^107,108,1411, Antisense oligonucleo tides^{1058,1407,1412–1421}	Proteins^182,196, ^457,1408, ^{1409,1422–1424}, Peptides^1410, ^1425,1426, Cytoplasmic extracts^468,498, ^1427–1442	Dextrans¹⁴⁰⁹	PNA probes^1443–1445, Molecular Beacons^1043, ^1446–1452, Photosensit izers¹⁴⁵³, Phosphatidi c acid¹⁴⁵⁴, Rb⁺ ions¹⁸², ATP¹⁸², Various RNA probes^1455–1457, Lanthanum probes^261,1458	Gold nanoparticl es¹⁴⁵⁹
	Membrane-Active Peptides
	Lipid Peroxidation			siRNA¹⁴⁶⁹
Gated Channels & Valves	Membrane Transporters & Channels				Proteins¹⁴⁸², Peptides¹⁴⁸²		Dyes^1470,1472, ^{1480,1485,1536,} ¹⁵³⁷, Ions¹⁴⁸¹, Trehalose²⁶⁶