Table 1.

Comparison of different methods for conjugation of DNA to quantum dots.

s.no	approach	modification on QD	modification on DNA	advantages	disadvantages	references
1	phospholipid encapsulation	organic ligands	amine/thiol	— one step procedure — compatible with range of synthesis — DNA retains hybridizability	— stability issues — large size of particles — random fusion with membranes — low QY	[7,8]
2	electrostatic attraction with polymer on QDs	positively charged hydrophilic ligands	unmodified; interaction with phosphate backbone	— rapid — high DNA loading efficiency — reversible	— difficult to control stoichiometry of DNA — issues with stability and aggregation	[65,68]
3	affinity for cationic shell of QDs	positively charged or neutral	thiol/polyhistidine/phosphorothioate	— rapid assembly — high yield — compact	— unstable in high dilutions — loss of DNA by photo-oxidation — pH sensitive — interactions with DNA backbone can cause conformational change — low QY due to charge transfer	[44–46,49,56]
4	affinity for specific ligand	streptavidin conjugation	biotinylated DNA	— fast and easy — conjugation of DNA independent of length — stoichiometric control — High QY	— increase in conjugate size due to presence of protein	[3,35,45,72,73,79]
		Ni-NTA modified	polyhistidine modified	— one step — efficient — high QY	— pH sensitive stability	[70]
5	covalent conjugation with ligands on QDs	QDs with carboxylic acids	amine modified	— highly stable — pH insensitive — DNA hybridization preserved — moderate-high QY	— multistep — low yield — nanoparticle size increases	[80–82]
		QDs with amines	thiol modified			[83]
		QDs with thiols	amine modified cyclooctyne			[84]
		QDs with azide		— reactants are not prone to hydrolysis	— loss of QY	[85]