DNA aptamer–micelle as an efficient detection/delivery vehicle toward cancer cells

Abstract

We report the design of a self-assembled aptamer-micelle nanostructure that achieves selective and strong binding of otherwise low-affinity aptamers at physiological conditions. Specific recognition ability is directly built into the nanostructures. The attachment of a lipid tail onto the end of nucleic acid aptamers provides these unique nanostructures with an internalization pathway. Other merits include: extremely low off rate once bound with target cells, rapid recognition ability with enhanced sensitivity, low critical micelle concentration values, and dual-drug delivery pathways. To prove the potential detection/delivery application of this aptamer-micelle in biological living systems, we mimicked a tumor site in the blood stream by immobilizing tumor cells onto the surface of a flow channel device. Flushing the aptamer-micelles through the channel demonstrated their selective recognition ability under flow circulation in human whole-blood sample. The aptamermicelles show great dynamic specificity in flow channel systems that mimic drug delivery in the blood system. Therefore, our DNA aptamer-micelle assembly has shown high potential for cancer cell recognition and for in vivo drug delivery applications.DNA aptamers | drug delivery | micelles | molecular specificity M any interesting nanomaterials, either natural or artificial, have been designed to perform unique functions through the process of molecular self-assembly. In nature, the apoptosome (1) is one such example. Individual apaf-1 protein does not have a biological function; however, when forming a complex with cytochrome-c, several individual proteins self-assemble into a wheel structure called an apoptosome. Once formed, the apoptosome can then recruit and activate the otherwise inactive procaspase-9 that can then activate other caspases and trigger a cascade of events leading to apoptosis. Learning from nature, chemists have created various artificial nanostructures. Micelle is one of such examples. Polymeric micelles have been subjected to extensive studies in the field of drug delivery, functioning as drug solibilizers and carriers (2). More recently, a micelle constructed as a hybrid from hydrophilic oligonucleotide and hydrophobic polymer (3, 4) has drawn close attention. In aqueous solutions, this type of amphiphilic block copolymer can self-assemble into a three-dimensional spherical micelle structure or a nanorod-like micelle structure. This type of micelle has been shown to efficiently carry a variety of cargos to cells, including antisense oligonucleotides (5) and drug molecules (6). To perform efficient targeted delivery, folic acid, a type of cancer cell recognition molecule modified on a piece of short, complementary DNA, was clicked onto the micelles based on Watson-Crick base pairing (6).Aside from Watson-Crick base pairing, single-stranded oligonucleotides can recognize other target molecules based on noncovalent interactions, such as hydrophobic interaction and hydrogen bonding. This type of oligonucleotide ligand is known as an ...

Nanothermodynamics Mediates Drug Delivery

“…One of its major sectors is nanoparticle drug delivery [1,3,6]. Nanotechnology-based drug delivery systems have emerged as promising platforms for targeting and destroying mainly cancer cells [7][8][9] via photodynamic therapy (PDT) that uses a combination of light sources, photosensitizers such as phthalocyanines, and specific targeting molecules and nano-carriers for localized therapies at the micro/nanoscale. Following light activation of photosensitizers, reactive oxygen species are released and eventually destroy cancer cells [10], after successful intracellular internalization via endocytosis and subsequent accumulation in the endosome/lysosome compartments of the cell.…”

Activatable aptamer probe for contrast-enhanced in vivo cancer imaging based on cell membrane protein-triggered conformation alteration

“…Various signal reporters have been adopted, including radioactive, magnetic, and fluorescent agents (9)(10)(11)(12)(13). Our group has demonstrated that near-infrared dye-labeled aptamers could effectively recognize cancer cells in vivo and achieve cancer imaging with high specificity (13).…”

Drug delivery systems based on nucleic acid nanostructures

“…Similarly to the DBC micelle system, aptamers recognizing Ramos cells were assembled into micelles through implementation of a hydrophobic moiety at one end of the ODN. Interestingly, due to the multimerization of the aptamer sequence an increased binding of the micelles compared to the pristine nucleic acid sequence was achieved [159].…”