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.

Significantly Improving the Bioefficacy for Rheumatoid Arthritis with Supramolecular Nanoformulations

“…Nanoparticle‐based therapy has attracted tremendous attention in arthritis and related‐biomedical communities over past few years. [ 18–23 ] Owing to its effective approach which provides protection of encapsulated payloads from degradation in the circulation, the formulation of drugs into nanoparticles has many potential advantages over conventional modalities especially in enhanced bioavailability and improved efficacy. [ 24,25 ] Typically, the nanotherapeutic with ambient particles size of 10–200 nm might effectively facilitate diffusion of the payloads and increase circulation half‐life.…”

“…[13,17] Thus, there is still largely unmet clinical need to prolong systemic circulation of the medication and increase bioavailability to realize long-acting effect and increase the drug regimen.Nanoparticle-based therapy has attracted tremendous attention in arthritis and related-biomedical communities over past few years. [18][19][20][21][22][23] Owing to its effective approach which provides protection of encapsulated payloads from degradation in the circulation, the formulation of drugs into nanoparticles has many potential advantages over conventional modalities especially in enhanced bioavailability and improved efficacy. [24,25] As a typical inflammatory disease with chronic pain syndromes, rheumatoid arthritis (RA) generally requires long-term treatment with frequent injection administration at 1-2 times per day, because common medications such as interleukin1 receptor antagonist (IL1ra) have poor bioavailability and very limited half-life residence.…”

Overcoming Barriers: Clinical Translation of siRNA Nanomedicines

“…Oligonucleotide self‐assembled nanoparticles based on DNA technology affords the rational design of unique geometric nanoparticles including tetrahedron or tubular shaped DNA nanoparticles. [ 142,143 ] Wang et al. demonstrated that tubular DNA nanoparticles co‐loaded with doxorubicin and two strands of siRNA targeting P‐gp and Bcl‐2.…”

“…demonstrated that tubular DNA nanoparticles co‐loaded with doxorubicin and two strands of siRNA targeting P‐gp and Bcl‐2. [ 143 ] The triple therapeutic delivery system demonstrated significant knockdown and tumor growth inhibition in MCF7‐resistant tumor‐bearing mice. [ 143 ] Biomimetic approaches have been of recent interest in drug delivery, utilizing biological vesicles or cellular membranes to enhance therapeutic delivery.…”

Information processing based on DNA toehold-mediated strand displacement (TMSD) reaction

“…The early works focused on the investigation of the fundamental properties of the DNA TMSD reaction such as controlling the kinetic property of the DNA TMSD reaction with the toehold domain, 18 together with the construction of basic logic information operations of AND, OR and NOT gates, 9 finite state machines for DNA transducer design, 22 and biological biped walking motors, 23 which were even designed with synchronized walking fashion. 24 Then, several complex reaction networks or patterns were devised to perform more sophisticated functions ranging from structure manipulation, [25][26][27][28] algorithm investigation such as half/full adder, 29 square-rooting function, [30][31][32] network communication, [33][34][35][36][37] DNA algorithm logic unit, 38 and oscillator, 39,40 to diagnostic therapy including drug delivery systems [41][42][43][44][45] and sensing. 20,25,[46][47][48][49][50][51][52][53][54][55]…”