A Controllable Aptamer-Based Self-Assembled DNA Dendrimer for High Affinity Targeting, Bioimaging and Drug Delivery

Abstract

Targeted drug delivery is important in cancer therapy to decrease the systemic toxicity resulting from nonspecific drug distribution and to enhance drug delivery efficiency. We have developed an aptamer-based DNA dendritic nanostructure as a multifunctional vehicle for targeted cancer cell imaging and drug delivery. The multifunctional DNA dendrimer is constructed from functional Y-shaped building blocks with predesigned base-pairing hybridization including fluorophores, targeting DNA aptamers and intercalated anticancer drugs. With controllable step-by-step self-assembly, the programmable DNA dendrimer has several appealing features, including facile modular design, excellent biostability and biocompatibility, high selectivity, strong binding affinity, good cell internalization efficiency, and high drug loading capacity. Due to the unique structural features of DNA dendrimers, multiple copies of aptamers can be incorporated into each dendrimer, generating a multivalent aptamer-tethered nanostructure with enhanced binding affinity. A model chemotherapeutic anticancer drug, doxorubicin, was delivered via these aptamer-based DNA dendrimers and exerted a potent toxicity for target cancer cells (human T cell acute lymphoblastic leukemia cell line) with low side effects for the non-target cells (human Burkitt’s lymphoma cell line). This controllable aptamer-based DNA dendrimer is a promising candidate for biomedical applications.

A multifunctional DNA origami as carrier of metal complexes to achieve enhanced tumoral delivery and nullified systemic toxicity

“…Researchers have developed the technique of tile and origami-based DNA hybridization to fabricate nanoscale projects with desired size and shapes, such as capital letters [10], dolphin [11], Chinese characters and 3 dimensional (3D) shapes including crystal lattices [12], spheres and screws [13]. With the development of DNA technology, DNA origami is considered as prospective candidate for drug delivery because it has unique advantages including (1) predictable and well-defined structure [14], (2) high efficacy of drug loading [15], (3) chemically modifiable for drug design [16], (4) stability in physiological M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 5 conditions [17] and (5) superior biocompatibility [18]. Högberg et al, fabricated DNA nanotubes to enhance the release rate and anti-proliferative effect of DOX in cancer cells [19].…”

Aptamers Chemistry: Chemical Modifications and Conjugation Strategies

“…Similarly, the base pairing cDNA-mediated dendrimer-aptamer conjugation strategy was also adapted in the conjugation of sgc8 to the three-armed Y-shaped dendritic DNA nanostructure. This formulation exerted strong toxicity for a human T-cell acute lymphoblastic leukemia cell line [214].…”

DNA Nanotechnology for Precise Control over Drug Delivery and Gene Therapy

“…Y shaped aptamers can also be used to for big multilayered DNA dendrimers (Figure 8 D). [ 94 ] By designing each layer of aptamers differently, the DNA dendrimers contain fl uorophores, targeting ligands (sgc8) and anticancer drugs (Dox) for imaging, cell recognition and drug delivery. This complex also showed potent toxicity towards target cancer cells (human T cell acute lymphoblastic leukemia cell line) while having low side effects for the non-target cells (human Burkitt's lymphoma cell line).…”