Table 2 Non-Covalent strategies for nucleic acid Conjugation on the surface of nanomaterials

Non-Covalent conjugation

Electrostatic attraction

Interaction between opposite charges

(1) Bond Strength: 20 kJ.mol⁻¹

(2) Electrostatic gravity is not directional and the interaction between anions and cations can be in any direction

Most positively charged nanomaterials

[44,45,46]

Hydrogen Bond, π-π interactions and van der Waals force

An attractive interaction between two molecular moieties in which at least one of them contains a hydrogen atom that plays a fundamental role

(1) Bond Strength: 12–30 kJ.mol⁻¹

(2) Hydrogen bonding is directional, saturated

(3) Hydrogen bonds are different from chemical bonds in that they have a small bond energy and a longer bond length

(4) π-π interactions are influenced by pH and redox conditions but maintain the chemical structure and biological activity of conjugated NAs

Carbon-based nanomaterials (graphene oxide, carbon nitride nanosheet),

COFs, MOFs

[47, 48]

Hydrophobic interaction

The phenomenon of hydrophobic groups aggregating in close proximity to each other to avoid water

(1) Bond Strength: < 40 kJ.mol⁻¹

(2) The hydrophobic interaction forces are generally stronger than the classical van der Waals forces and exhibit a large range of effects

PEGylated liposomes,

Lipid Nanoparticles, MNPs

[49,50,51]

Biotin-streptavidin

Streptavidin tetramers have a positive effect on biotin Extremely high binding affinity

(1) One streptavidin protein is able to bind four biotin molecules with high affinity and selectivity

(2) The affinity constant of avidin-binding biotin can be millions of times that of antigen–antibody reaction, and the dissociation constant of the complex formed by the combination of the two is very small, irreversible reactivity, and strong stability

(3) Thermal instability (> 75 °C)

Carbon nanoparticles, AuNPs, magnetic nanobeads, SiNPs

[52,53,54,55]

Base affinity

The unique binding force of polynucleotides to certain nanomaterials

(1) Oligonucleotides do not require additional modifications

(2) It belongs to the non-specific adsorption of DNA and is base-dependent

(3) It is convenient to control the density of DNA conjugation

AuNPs, carbon-based nanomaterials, ZnO NPs

[56,57,58]