Structures and Applications of Nucleic Acid-Based Micelles for Cancer Therapy

Abstract

Nucleic acids have become important building blocks in nanotechnology over the last 30 years. DNA and RNA can sequentially build specific nanostructures, resulting in versatile drug delivery systems. Self-assembling amphiphilic nucleic acids, composed of hydrophilic and hydrophobic segments to form micelle structures, have the potential for cancer therapeutics due to their ability to encapsulate hydrophobic agents into their core and position functional groups on the surface. Moreover, DNA or RNA within bio-compatible micelles can function as drugs by themselves. This review introduces and discusses nucleic acid-based spherical micelles from diverse amphiphilic nucleic acids and their applications in cancer therapy.

Keywords: DNAs; RNAs; amphiphiles; chemotherapy; gene silencing; immunotherapy; nanoparticles; targeting.

Figure 1

Schematic representation of a nucleotide, double-stranded DNA, and amphiphilic DNA. The nucleotide structure, including a phosphate, a sugar, and a base, is presented on the left. The structural difference between deoxyribose and ribose is shown below the nucleotide structure. The chemical structure of five nucleobases is presented at the top. A detailed structure of double-stranded DNA, composed of two chemically synthesized oligodeoxyribonucleotides, is presented on the right side. The 5’-end and 3’-end indicate the anti-parallel directionality of dsDNA. The dotted lines denote the hydrogen bonds between nucleobases. The positions of hydrophobic segments in amphiphilic DNA are shown at the bottom.

Figure 2

Outline of this review dealing with nucleic acid micelles.

Figure 3

Different types of DNA micelles. (A,B). Hydrophobic molecule-DNA micelles. (A). Schematics of the DNA–Drug (Camptothecin; CPT) micelles assembled from DNA–Drug amphiphiles. Reproduced from ref. [28]. (B). Self-assembly of DNA amphiphiles into micelles in aqueous media. Reproduced from ref. [29]. (C). A hydrophobic polymer-DNA micelle. Self-assembly of DNA diblock copolymer amphiphiles into a micelle. Reproduced from ref. [34]. (D). Lipid-DNA micelle. The design of a lipid-DNA amphiphile and the assembly of DNA micelles. Reproduced from ref. [36]. (E). A lipid-modified DNA micelle. Schematic representation of lipid-modified DNA amphiphiles. The number and position of the lipid-modified nucleobase are indicated as the number and M/T, respectively. Reproduced from refs. [44,45].

Figure 4

Different types of RNA micelles. (A). Schematics of the three-way junction micelles by hydrophobic interaction of cholesterol in aqueous media. Reproduced from ref. [46]. (B). Schematic illustration of an RNA micelle. Reproduced from ref. [49]. (C). The design of self-assembled micelle inhibitory RNA (SAMiRNA). Reproduced from ref. [50].

Figure 5

Schematic illustration shows the aptamer-nucleic acid micelle targeting cancer cells through aptamer-receptor recognition (reproduced from ref. [52]).

Figure 6

Diverse chemotherapeutic micelles. (A). Folic acid (FA) functionalized and doxorubicin (DOX) loaded micelle (ref. [45]) (B). Buparlisib (BKM120) loaded micelle (ref. [53]) (C). Mucine1 aptamer (anti-MUC1) functionalized, and (KLAKLAK)2 (KLA) and DOX loaded micelle (ref. [39]) (D). Camptothecin (CPT) loaded micelle (ref. [28]) (E). Paclitaxel (PTX) and anti-MUC1 functionalized micelle (ref. [46]) (F). Floxuridine micelle (ref. [54]).

Figure 7

Schematic representation of nucleic acid-based micelle’s immunotherapy. Reproduced from ref. [55].