Schematic representation of designed DNA nanostructure grafted with erlotinib and enhanced inhibition of tumor growth for non-small-cell lung cancer (NSCLC).
interact with nuclear DNA and form intraor interstrand crosslinks, thus elicit DNA replication inhibition and cell death. [3,4] However, platinum-based therapy has some disadvantages, such as severe side effects (nephrotoxicity, ototoxicity, and neurotoxicity) and easily acquired drug resistance. [5,6] Though the mechanism of cisplatin resistance is reported to be multifactorial, reduced intracellular cisplatin accumulation is supposed to be the major reason. [7,8] Compared with Pt(II) species, Pt(IV) prodrugs are more inert and more stable in biological environment, thus avoid deactivation by proteins or other biomolecules and reduce side effects. Pt(IV) complexes are reduced more likely in reductive tumor environment to yield cytotoxic Pt(II) drugs. [9-11] Thus, Pt(IV) prodrugs are ideal alternatives to the existing Pt(II) drugs. With the rapid development of nanotechnology, nanoscale drug delivery systems (DDSs) have become an important field of medical research. DDSs have been reported to be a promising strategy to overcome problems associated with platinum-based treatment because of their more active cellular uptake and more accurate tumor localization. [12,13] Nowadays, a variety of DDS have been developed for Pt(IV) prodrug delivery, [14] including gold nanoparticles, [15,16] mesoporous silica nanoparticles, [17,18] carbon nanotubes, [19,20] and so on. [21-23] In recent years, DNA nanostructures have been developed to be a promising candidate for anticancer drug delivery. [24] Compared with traditional inorganic and organic nano particles, DNA nanostructures have many advantages, such as wellcontrolled 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). [42] But so far, to our best knowledge, DNA nanostructures for Pt(IV) prodrug delivery have not been reported. Herein, we constructed three DNA nanostructures with varied sizes and shapes and studied their potential as Pt(IV) Cisplatin is a first-line drug in clinical cancer treatment but its efficacy is often hindered by chemoresistance in cancer cells. Reduced intracellular drug accumulation is revealed to be a major mechanism of cisplatin resistance. Nanoscale drug delivery systems could help to overcome this problem because of their more active cellular uptake and more accurate tumor localization. DNA nanostructures have emerged as promising drug delivery systems because of their intrinsic biocompatibility and structural programmability. Herein, three diverse DNA nanostructures are constructed and their potential for cisplatin prodrug delivery is investigated. Results found that these D...
Transdermal drug delivery approach has been considered a potential therapy for human hypertrophic scar (HS) instead of current uncomfortable surgical excision, local injection and laser therapy. However, a facile and...
Most anticancer drugs, particularly paclitaxel (PTX), are suffering the challenges of cancer chemotherapy due to their poor water-solubility, high toxicity under effective therapeutic dosages, and multi-drug resistance. Currently, nanoscale drug delivery systems (DDSs) represent an efficient platform to overcome the above challenges. However, those DDSs generally need a careful design of conjugation, complexation, or co-self-assembly. Herein, a facile out-of-the-box nanocapsule is developed not only to be easily packed with on-demand hydrophobic anticancer drugs (up to 76% of loading efficiency for PTX), but also to be loaded with other concomitant drugs for synergy therapy (Itraconazole (ITA) here as P-glycoprotein inhibitor for drug resistance and antiangiogenic agent for combination therapy with PTX). Three kinds of biocompatible poly(ethylene glycol) dimethacrylates (PEGDM) derivatives usually as cross-linking agents are selected and successfully constructed adequate nanocapsules with single monomer as shell materials. More importantly, as-prepared nanocapsules have abilities of esterase triggering and lung targeting. Both in vitro and in vivo studies showed that the drug-loaded nanocapsules can effectively inhibit tumor growth and vascular proliferation in PTX-resistant tumor models without apparent systemic toxicity. The above results demonstrate that the nanocapsule system provides an effective and universal strategy for lung targeting, esterase triggering, and synergy therapy.
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