A Camptothecin‐Grafted DNA Tetrahedron as a Precise Nanomedicine to Inhibit Tumor Growth

Abstract

Most chemotherapeutics are hydrophobic molecules and need to be converted into hydrophilic form before administration. Based on the excellent hydrophilicity and programmability of DNA, now,ageneral strategy to construct ap recise drug-containing DNAf ramework for cancer treatment is reported. In this novel drug delivery system, carbonethyl bromide-modified camptothecin (CPT) is employed to directly react with phosphorothioate (PS) modified DNAs, resulting in the formation of chemotherapeutics-grafted DNAs with aresponsive disulfide linkage.Bytuning the number and site of PS modifications on DNAstrands,hydrophilicity of the obtained DNA-drug conjugates (DDCs) can be regulated to retain their aqueous solubility and capability of molecular recognition. Subsequently,p rogrammable DNAn anotechnology enables the self-assembly of ap recise drug-containing tetrahedral framework with stimuli-responsive feature and enhanced antitumor efficacy both in vitro and in vivo.

Self‐Assembled Nanoparticles as Cancer Therapeutic Agents

“…conjugated CPT onto four programed DNA strands which are complementary with each other and finally self‐assemble into nanocomplexes via base‐pairings recognition, the resulting NPs could be efficiently taken up into cells and release CPT by GSH. [ 85 ] The similar work was carried out by Zhu et al. that floxuridine was first covalently introduced to complementary DNA strands, then self‐assembled into nanosized polyhedra and those with buckyball morphology have the best anticancer efficiency.…”

DNA Nanostructures and DNA‐Functionalized Nanoparticles for Cancer Theranostics

“…Further, the self-assembled DNA-NSs exhibited a decreased tumor growth rate in vivo. [118] Recently, Wu et al constructed an EGFR nanobody-conjugated DNA-NS-based carrier of 56MESS, a platinum-based intercalator for targeted delivery in vivo (Figure 13). [119] Interestingly, by exploiting the base-pairing properties of DNA, the double-bundle DNA tetrahedron was able to arrange anti-EGFR nanobodies in a highly organized manner to achieve successful targeting.…”

DNA Nanostructures as Pt(IV) Prodrug Delivery Systems to Combat Chemoresistance

“…[ 24 ] Compared with traditional inorganic and organic nanoparticles, DNA nanostructures have many advantages, such as well‐controlled structure, addressable modification sites, and good biocompatibility. [ 25–29 ] By covalently or noncovalently loading, a variety of DNA nanoplatforms have been reported to be effective carriers for small molecular drugs, [ 30–34 ] gene therapeutic agents, [ 35–37 ] and proteins. [ 38–40 ] In particular, a DNA‐icosahedron was reported to precisely deliver platinum nanodrugs to cisplatin‐resistant cancer, [ 41 ] and a DNA tetrahedron was constructed for targeted delivery of the platinum drug 56MESS (a Pt(II)‐based DNA intercalator).…”