A Tubular DNA Nanodevice as a siRNA/Chemo‐Drug Co‐delivery Vehicle for Combined Cancer Therapy

Abstract

Using the DNA origami technique, we constructed a DNA nanodevice functionalized with small interfering RNA (siRNA) within its inner cavity and the chemotherapeutic drug doxorubicin (DOX), intercalated in the DNA duplexes. The incorporation of disulfide bonds allows the triggered mechanical opening and release of siRNA in response to intracellular glutathione (GSH) in tumors to knockdown genes key to cancer progression. Combining RNA interference and chemotherapy, the nanodevice induced potent cytotoxicity and tumor growth inhibition, without observable systematic toxicity. Given its autonomous behavior, exceptional designability, potent antitumor activity and marked biocompatibility, this DNA nanodevice represents a promising strategy for precise drug design for cancer therapy.

Electrospun Polymeric Fibers Decorated with Silk Microcapsules via Encapsulation and Surface Immobilization for Drug Delivery

“…Upon the interaction with intracellular glutathione (GSH) in tumors, the DNA locks containing “disulfide bond” were cleaved, resulting in structural changes in the nanodevices and the release of loaded siRNA and drugs. [ 36 ] Therefore, the use of cleavable linkers makes the drug vehicle release more specific and targeted, which is beneficial to improve the therapeutic effect in different pathological microenvironments.…”

Logic devices based on nucleic acid self‐assembly

“…Taking advantage of the logic-gated strategy, the cell discrimination properties of DNA/RNA drug carriers can be enhanced and the off-target effects could be reduced. 24,108 In the future, biological circuitries constructed by nucleic acids could even be designed to process multiplexed physiological/pathological information in vivo, releasing loaded drugs on-site and regulating the expression of specific genes.…”

Cancer-cell-membrane-camouflaged supramolecular self-assembly of antisense oligonucleotide and chemodrug for targeted combination therapy

“…[1][2][3][4][5] However, the easy degradation to nucleases, nonspecific interaction with proteins, unwanted immune recognition, short circulation time, low cellular uptake and poor endosomal escape of naked oligonucleotide drugs hinder their clinical translation. [6][7][8][9] To address these issues, various delivery vectors, [10][11][12][13] including cationic liposomes, polymers, [14][15][16][17] peptide-based materials, 18 nucleic acid nanostructures, 19,20 spherical nucleic acid structures, 21,22 inorganic nanoparticles, 23,24 polyplex nanogels 25 and bottlebrush-architecture poly(ethylene glycol) 26 have been developed to enhance the physiological stability, reduce non-specific protein interactions and immune response, improve blood circulation time during delivery and enhance intracellular uptake of nucleic acid drugs in tumor sites. However, biosafety concerns related to carriers for oligonucleotide drug delivery remain.…”