Biocompatible Infinite‐Coordination‐Polymer Nanoparticle–Nucleic‐Acid Conjugates for Antisense Gene Regulation

Abstract

Herein, we report the synthesis of DNA-functionalized infinite coordination polymer (ICP) nanoparticles as biocompatible gene regulation agents. ICP nanoparticles were synthesized from ferric nitrate and a ditopic 3-hydroxy-4-pyridinone (HOPO) ligand bearing a pendant azide. Addition of FeIII to a solution of the ligand produced nanoparticles, which were colloidally unstable in the presence of salts. Conjugation of DNA to the FeIII-HOPO ICP particles, via copper-free click chemistry, afforded colloidally stable nucleic acid nanoconstructs. The DNA-ICP particles, when cross-linked through sequence-specific hybridization, exhibit narrow, highly cooperative melting transitions consistent with dense DNA surface loading. The ability of the DNA-ICP particles to enter cells and alter protein expression was also evaluated. Our results indicate these novel particles carry nucleic acids into mammalian cells without the need for transfection agents and are capable of efficient gene knockdown.

A DNA dual lock-and-key strategy for cell-subtype-specific siRNA delivery

“…A variety of materials have been explored as siRNA delivery carriers, such as liposomes, cationic polyelectrolytes and inorganic nanoparticle171819. However, these conventional delivery vehicles suffer from low loading efficiency, less cell-specific manner, complex surface modification process and/or the damage of immunogenic response or toxicity2021.…”

Therapeutic Applications of Spherical Nucleic Acids

“…SNAs can be composed of a variety of oligonucleotides (e.g., DNA, siRNA, microRNA, peptide nucleic acid (PNA), or locked nucleic acid (LNA)) and a variety of different types of nanoparticle cores, such as gold (Au) [34], silver (Ag) [46], iron oxide (Fe 3 O 4 ) [47,48], quantum dots (CdSe, CdSe/ZnS) [49,48], platinum [48], silica (SiO 2 ) [50], core-shell (Au@SiO 2 ) [50], and liposomes [51] typically ranging in size from 10 to 50 nm. Coreless versions of these structures can also be made that display the same useful properties as the core-filled structures, emphasizing the concept that the properties of SNAs stem from their densely functionalized and highly oriented nucleic acid shell and not from the nanoparticle core [51][52][53][54]. Some types of the hollow SNAs that have been synthesized thus far include those consisting of cross-linked oligonucleotides [53], DNA-block copolymer micelles [55,56], infinite coordination polymers [52], metal organic frameworks [54], and liposomes [51].…”

“…Coreless versions of these structures can also be made that display the same useful properties as the core-filled structures, emphasizing the concept that the properties of SNAs stem from their densely functionalized and highly oriented nucleic acid shell and not from the nanoparticle core [51][52][53][54]. Some types of the hollow SNAs that have been synthesized thus far include those consisting of cross-linked oligonucleotides [53], DNA-block copolymer micelles [55,56], infinite coordination polymers [52], metal organic frameworks [54], and liposomes [51]. Hollow SNAs, such as the liposomal SNAs, represent an exciting new class of metal-free SNAs that can be useful in gene regulation, and their potential is only beginning to be realized [51].…”

Nanoflares as Probes for Cancer Diagnostics

“…SNAs can be prepared with inorganic cores (silver [14], gold [15], iron oxide [16], quantum dots [17], silica [18], infinite coordination polymers [19]) or be coreless (cross-linked alkyne polymers [20], liposomes [21]) in nature. However, SNAs with gold particle cores are most commonly used in gene detection assays involving nanoflares because gold is inert and has the ability to quench fluorescent molecules in a distancedependent manner [9].…”