Out-of-the-Box Nanocapsules Packed with On-Demand Hydrophobic Anticancer Drugs for Lung Targeting, Esterase Triggering, and Synergy Therapy.

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.

DNA hydrogel-based gene editing and drug delivery systems.

Deoxyribonucleic acid (DNA) is a promising synthesizer for precisely constructing almost arbitrary geometry in two and three dimensions. Among various DNA-based soft materials, DNA hydrogels are comprised of hydrophilic polymeric networks of crosslinked DNA chains. For their properties of biocompatibility, porosity, sequence programmability and tunable multifunctionality, DNA hydrogels have been widely studied in bioanalysis and biomedicine. In this review, recent developments in DNA hydrogels and their applications in drug delivery systems are highlighted. First, physical and chemical crosslinking methods for constructing DNA hydrogels are introduced. Subsequently, responses of DNA hydrogels to nonbiological and biological stimuli are described. Finally, DNA hydrogel-based delivery platforms for different types of drugs are detailed. With the emergence of gene therapy, this review also gives future prospects for combining DNA hydrogels with the gene editing toolbox.

Designed DNA nanostructure grafted with erlotinib for non-small-cell lung cancer therapy.

Chemotherapy for non-small-cell lung cancer (NSCLC) treatment has been employed over the past 20 years. However, poor water-solubility, low bioavailability and less drug accumulation of chemotherapeutic drugs restrict its antitumor activities in clinic. DNA nanostructures are proposed as drug carriers due to their intrinsic biocompatibility and programmability. In this work, we demonstrate a novel DNA nanocarrier grafted with erlotinib as an effective drug delivery system (DDS) for anti-cancer treatment. Specifically, erlotinib (Er), a hydrophobic small molecule drug targeting the epidermal growth factor receptor (EGFR), is covalently conjugated with azide (N3) modified DNA strands and subsequently self-assembled on spatially programmable erlotinib-grafted 6 × 6 × 64 nt DNA nanostructures. Thus, Er was successfully grafted on DNA carriers and transformed into a hydrophilic formulation. The antitumor efficacy was evaluated both in vitro and in vivo, and enhanced cytotoxicity toward A549 cells and the marked inhibition of tumor growth for non-small-cell lung cancer (NSCLC) were observed.

A facile and efficient approach for hypertrophic scar therapy via DNA-based transdermal drug delivery.

The transdermal drug delivery approach has been considered a potential therapy for human hypertrophic scars (HSs) instead of current uncomfortable surgical excision, local injection and laser therapy. However, a facile and efficient drug delivery method is urgently needed to overcome the skin barrier of transdermal administration. Herein, we employed a DNA-Fe nanoparticle delivery system via Fe ion driven self-assembly to satisfy the requirement of transdermal administration for HS therapy. Doxorubicin hydrochloride (DOX) as one of the widely used anticancer drugs was employed to treat the hyperplasia of abnormal skin fibrous tissue. Both in vitro and in vivo experiments of the DOX loaded DNA-Fe nanoparticles (DOX@DNA-Fe NPs) were performed to demonstrate the penetration ability, rapid drug release, and scar-inhibiting effects. This facile and efficient approach for HS therapy via a DNA-based transdermal drug delivery system may provide more possibilities for the development of transdermal administration.

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

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 DNA nanostructures could remarkably enhance the cellular internalization of platinum drugs and thus increase the anticancer activity, not only to regular lung cancer cells (A549), but more importantly to cisplatin-resistant cancer cells (A549cisR). Further, in vivo studies also demonstrate that cisplatin prodrug loaded DNA nanostructures could effectively suppress tumor growth in both regular and cisplatin-resistant tumor models. This study suggests that DNA nanostructures are effective carriers for platinum prodrug delivery to combat chemoresistance.