Engineering Stability-Tunable DNA Micelles Using Photocontrollable Dissociation of an Intermolecular G-Quadruplex

Abstract

Because of their facile preparation, small size (<100 nm), programmable design, and biocompatibility, lipid-based DNA micelles show enormous potential as a tool to monitor biological events and treat human diseases. However, their structural stability in biological matrices suffers from spatiotemporal variability, thus limiting their in vivo use. Herein, we have engineered stability-tunable DNA micelle flares using photocontrollable dissociation of intermolecular G-quadruplexes, which confers DNA micelle flares with robust structural stability against disruption by serum albumin. However, once exposed to light, the G-quadruplex formation is blocked by strand hybridization, resulting in the loss of stability in the presence of serum albumin and subsequent cellular uptake. This programmable regulation to stabilize lipid-based micelles in the presence of fatty-acid-binding serum albumin should further the development of biocompatible DNA micelles for in vivo applications.

Amphiphilic DNA Organic Hybrids: Functional Materials in Nanoscience and Potential Application in Biomedicine

“…The loading approach based on the virus-like particles is probably to be utilized as a high-impact drug delivery system. Similar to the reported results [28,29], the DNA–lipid assemblies with G-quadruplex structures were stable enough in the presence of the serum albumin and the subsequent cellular uptake was achieved through DNA hybridization, which suggested these biocompatible DNA micelles as nanocarriers for cargo release in vivo applications.…”

“…By DNA hybridization, DNA–lipid conjugates desorbed from LC-aqueous interface into aqueous, resulting in the disappearance of net-like structures [27]. In 2017, Tan group developed the stability-tunable DNA micelles from DNA-lipid conjugates [28]. As shown in Figure 1, the DNA sequence contains the photocontrollable dissociation of intermolecular G-quadruplexes, which confers the DNA micelles with robust structural stability against disruption by serum albumin.…”

“…Purple core inside of the micelle stands for hydrophobic lipid core. Reproduced with permission from authors of a previous paper [28]. Copyright 2017 American Chemical Society.…”

Floxuridine Homomeric Oligonucleotides “Hitchhike” with Albumin In Situ for Cancer Chemotherapy

“…A lipid tail with two octadecyl chains inserts into the hydrophobic core of albumin by hydrophobic interaction. [6, 8a, 14] As such, upon intravenous injection, LFU20 noncovalently bonds with albumin in situ to form an LFU20/albumin complex. LFU20/albumin accumulates in the tumor by the EPR effect and internalizes into the lysosomes of cancer cells by the Gp18/Gp30-mediated pathway.…”

“…As shown in Figures 1c and S13, upon the addition of BSA, almost all Py-LFU20 micelles had dissociated within one minute to form Py-LFU20/albumin. Py-G8-LFU12 micelles, which have intermolecular G-quadruplexes in the micellar corona to stabilize the micellar structure, [14] showed only 48% formation of Py-G8-LFU12/albumin, even after one hour of incubation (Figure S13f). Apart from BSA, 0.5 mM human serum albumin (HSA) and 10% mice blood also induce effective formation of LFU20/albumin complex (Figures S14 and S15).…”