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Published on: June 26, 2019
Designed DNA nanostructure grafted with erlotinib for non-small-cell lung cancer therapy
Yuqi Wang1, Jin Cheng, Di Zhao
1School of Materials Science and Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.
Abstract:
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.
Insights
Researchers developed a novel DNA nanocarrier system for non-small-cell lung cancer (NSCLC) treatment. This system improves erlotinib delivery, enhancing anti-cancer efficacy and reducing tumor growth.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Chemotherapy for non-small-cell lung cancer (NSCLC) faces challenges due to poor drug solubility, bioavailability, and accumulation.
- DNA nanostructures offer biocompatible and programmable platforms for drug delivery.
Purpose of the Study:
- To develop a novel DNA nanocarrier system for improved delivery of erlotinib (Er) in anti-cancer treatment.
- To enhance the solubility and efficacy of the hydrophobic drug erlotinib for non-small-cell lung cancer therapy.
Main Methods:
- Erlotinib (Er) was covalently conjugated to azide-modified DNA strands.
- DNA nanostructures were self-assembled with erlotinib-grafted DNA strands to create a drug delivery system (DDS).
- Antitumor efficacy was evaluated in vitro using A549 cells and in vivo in non-small-cell lung cancer models.
Main Results:
- Erlotinib was successfully grafted onto DNA nanocarriers, transforming it into a hydrophilic formulation.
- Enhanced cytotoxicity was observed against A549 cancer cells in vitro.
- Significant inhibition of tumor growth was demonstrated in vivo for non-small-cell lung cancer.
Conclusions:
- The novel DNA nanocarrier system effectively delivers erlotinib for non-small-cell lung cancer treatment.
- This DDS demonstrates improved antitumor activity and potential for clinical application in NSCLC therapy.
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