A Tailored DNA Nanoplatform for Synergistic RNAi‐/Chemotherapy of Multidrug‐Resistant Tumors

Abstract

Multidrug resistance (MDR) is am ajor obstacle in the clinical treatment of cancer.H erein, af acile strategy is reported to construct av ersatile DNAn anostructure as ac odelivery vector of RNAi nterference (RNAi)a nd chemodrugs to combat multidrug-resistant tumor (MCF-7R) in vitro and in vivo.I nt he tailored nanocarrier,t wo linear small hairpin RNA( shRNA) transcription templates targeting MDR-associated genes (gene of P-glycoprotein, at ypical drug efflux pump;a nd gene of survivin, ar epresentative anti-apoptotic protein) are precisely organized in the chemodrug (doxorubicin, DOX) pre-loaded DNAo rigami. With the incorporation of active targeting and controlled-release elements,t hese multifunctional DNAn anocarriers can successfully enter the target MCF-7R cells and synergistically inhibit tumor growth without apparent systemic toxicity.T his tailored DNAn anoplatform, whichc ombines RNAi therapya nd chemotherapy, provides anew strategy for the treatment of multidrug-resistant tumors.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

A Nanobody‐Conjugated DNA Nanoplatform for Targeted Platinum‐Drug Delivery

“…[3] Theo bserved systemic toxicity and drug resistance induced by high doses of platinum drugs have led to the development of novel strategies to improve drug delivery efficacya nd circumvent drug resistance. [9] Functional groups can be precisely arranged on DNAn anocarriers to afford properties vital to targeted delivery and controlled release.Chemotherapeutic drugs, [10] gene therapy elements, [11] imaging probes, [12] and functional proteins [13] can be integrated into these multifunctional DNAnanoplatforms.Based on these tailored properties of the DNAn anostructures,w e hypothesized that platinum drugs,s uch as the DNAi ntercalator 56MESS,w hich possesses an aromatic ring structure, [14] can be efficiently loaded and delivered by am ultifunctional DNAn anoplatform. [8] DNAn anostructures,s uch as DNAp olyhedrons,h ave demonstrated excellent biocompatibility and high drug-loading capability and have been employed to efficiently enrich therapeutic drug concentration in tumor regions.…”

Nucleic Acid–Based Functional Nanomaterials as Advanced Cancer Therapeutics

“…Ding and coworkers have developed a series of DNA origami as nanocarriers for drug delivery . For example, they reported two types of DNA origami nanostructures, a tubular shape and a triangular shape, for DOX delivery ( Figure a) .…”

Multifunctional DNA Origami Nanoplatforms for Drug Delivery

“…RNAi is a tailored technology to knock down the expression of MDR‐related genes. Ding and co‐workers employed the DNA origami nanoplatform to load and deliver small hairpin RNA (shRNA) transcription templates that targeted MDR‐associated genes P‐gp and Survivin (Figure c) . The Dox and shRNA transcription templates for coloading DNA origami with aptamer modifications can efficiently enter target cells and induce a remarkable antitumor effect.…”

“…Ding and co-workers employed the DNA origami nanoplatform to load andd elivers mall hairpin RNA (shRNA) transcription templates that targeted MDR-associated genes P-gp and Survivin (Figure 7c). [54] The Dox and shRNA transcription templates for coloading DNA origami with aptamer modificationsc an efficiently enter target cells and induce ar emarkable antitumor effect. This multifunctional DNA origami nanoplatform can achieve the synergistic inhibition of tumor growth against multidrug-resistantt umors in vivo.…”