A controllable aptamer-based self-assembled DNA dendrimer for high affinity targeting, bioimaging and drug delivery.

Huimin Zhang,Yi Xie,Zhi Zhu,Yishun Huang,Yanli Ma,Yuan An,Chaoyong James Yang

doi:10.1038/srep10099

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.

Highlights

Chemotherapy is widely used for cancer treatment using traditional small molecule drugs
Uniform sized DNA tetrahedrons equipped with immune-stimulatory CpG oligonucleotides or small interface RNA have shown enhanced intracellular immunoregulation or gene delivery with excellent biostability and biocompatibility[12,13] Likewise, triangular DNA origami loaded with the anticancer drug doxorubicin exhibited improved anti-tumor efficacy and lower systemic toxicity in vivo compared to anti-cancer drugs[14]
DNA dendrimers were prepared from three-armed Y-shaped DNA monomers using an enzyme-free, step-by-step base-pairing assembly strategy[23]

Summary

Introduction

Chemotherapy is widely used for cancer treatment using traditional small molecule drugs. Nanotechnology applied in medicine, known as nanomedicine, has become a promising approach for efficient cancer therapeutics This technology uses precisely engineered materials at the scale of 1–100 nm to develop novel therapeutic and diagnostic modalities[4,5]. Passive delivery is useful for cancers with leaky vasculatures, it is not suitable for other types of cancers, such as leukemia, that require specific targeting. In this regard, incorporation of a ligand which targets a particular cell receptor to facilitate receptor-mediated endocytosis could provide enhanced versatility for the treatment of a variety of diseases[18]. Combined with the dendritic DNA structures and designed hybridization, it is possible to embed a variety of ligands and functional reagents to generate multifunctional nano-platforms

Methods

Results

Conclusion