DNA Nanogel for Cancer Therapy

Abstract

DNA nanogel exhibits properties of both the DNA and hydrogel, for example, remarkable biocompatibility, programmability, high drug loading capacity, and rapid stimuli‐responsive nature to microenvironment, which make it a potential ideal carrier for drug and gene delivery. In this review, DNA nanogels are categorized into two types, that is, rolling circle amplification‐based nanogel and hybridization‐based nanogel. Construction methods, design ideas for different functions, and applications in chemotherapy, gene therapy, and immunotherapy of nanogels are discussed. It is believed that this review will help readers to have a deeper understanding of the basic design strategies of DNA nanogels for specific targeting, loading of various anticancer agents, and stimuli‐responsive degradation of nanogels for the controlled release of drugs, which will ultimately help to design more effective delivery system for better therapeutic effects. It is very likely that DNA nanogel, as an intelligent drug carrier, will play a greater role in cancer treatment in future.

Recent advances in stimuli-responsive tailored nanogels for cancer therapy; from bench to personalized treatment

“…[13][14][15] Since they can release drugs at the target site, they can detect changes in the tumor microenvironment and their ability to respond to stimuli makes them particularly useful in personalized cancer therapy. 16,17 Bio-responsive NGs are advanced delivery systems for anticancer drugs because they have excellent stability and safety profiles and immediately respond to biological stimuli 18 especially for drugs like proteins, 19 siRNA 20 and DNA 21,22 resulting in massively improved tumor therapy. Furthermore, NGs maintain a highly hydrated state and shrinking-swelling characteristics under environmental conditions.…”

“…Bio-responsive NGs are advanced delivery systems for anticancer drugs because they have excellent stability and safety profiles and immediately respond to biological stimuli 18 especially for drugs like proteins, 19 siRNA 20 and DNA 21,22 resulting in massively improved tumor therapy. Furthermore, NGs maintain a highly hydrated state and shrinking–swelling characteristics under environmental conditions.…”

Supramolecular DNA nanogels through host–guest interaction for targeted drug delivery

“…DNA hydrogels are emerging biomaterials with good stability, flexibility, precise programmability and biocompatibility. [1][2][3][4][5] During recent decades, while the functional nucleic acids such as aptamers, 6 i-motif structures, 7 and CpG oligodeoxynucleotides 8 have been introduced into DNA hydrogels to provide multiple functions, 9 chemical functional groups or functional nanoparticles 10,11 have also been integrated into DNA hydrogels to widen their biological applications. [12][13][14][15][16] Recently, nanoscale DNA hydrogels, known as DNA nanogels, have been precisely prepared.…”

“…24 Among these, the CB[n] (n = 5-8, 10, 13-15) family, as the fourth generation supramolecular macrocycle host molecules, has the following advantages in the construction of supramolecular hydrogels: (1) low cytotoxicity; [25][26][27][28] (2) with different cavity sizes of CB[n]s, they can form complexes with controllable numbers of guest molecules; 29 (3) the high affinity between CB[n]s and guest molecules 30 guarantees the stability of the guest molecule, especially hydrophobic drugs; 22 (4) the host-guest interaction is dynamically reversible by introducing external stimuli such as light, 31 pH, 32 FGG peptide, 33 etc. (5) the guest molecule could be functional, which introduces more functionality in the hydrogels. All these advantages indicate that the host-guest interaction between CB[n]s and guest molecules will be an effective strategy to construct supramolecular DNA nanogels.…”

ROS-Responsive Self-Degradable DNA Nanogels for Targeted Anticancer Drug Delivery

“…Herein, we developed a reactive oxygen species (ROS)-responsive self-degradable drug delivery system (DN-DNBC) by introducing a nitrophenyl tetramethyldioxaborolanylbenzylcarbamate (NBC)-modified DNase I (denoted as DNBC) into an aptamer-decorated DNA nanogel (DN) through physical encapsulation for targeted anticancer drug delivery (Scheme ). The nanogel was generated by complementary base pairing of three kinds of DNA building blocks, i.e., Y-shaped monomer 1 (Y1) with three sticky ends, Y-shaped monomer 2 (Y2) with two sticky ends and an aptamer end, and a DNA linker (L) with two sticky ends. ,− DOX and ribonuclease A (RNase A) were used as two representative agents to evaluate the application potential of DN-DNBC nanogels as drug delivery vehicles. DOX is a commonly used chemotherapeutic agent for cancer therapy, while RNase A is a basic cytotoxic protein that can induce cancer cell death by degrading intracellular RNA .…”