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Docetaxel gold complex nanoflowers: A chemo-biological evaluation for their use as nanotherapeutics
Maroua Ben Haddada1, Dania Movia2, Adriele Prina-Mello3
1CNRS, UMR 7244, CSPBAT, Laboratoire de Chimie, Structures et Propriétés de Biomatériaux et d'Agents Thérapeutiques Université Paris 13, Sorbonne Paris Cité, Bobigny, France.
Abstract:
Docetaxel (DTX) is an anticancer treatment widely used in the clinic for the treatment of various human malignancies, including Non-Small-Cell Lung Cancer (NSCLC). Its low water solubility and systemic toxicity, however, negatively impact the clinical application of such drug. In order to improve DTX solubility in biological fluids and decrease its adverse effects in patients, the scientific community is currently focusing on developing drug delivery systems where DTX is the payload. In this context, the present study aims at presenting a step forward in the development of platforms based on gold complexes for multifunctional approaches (theragnostic tools) and stimuli-responsive therapies. Tetrachloroauric acid (HAuCl4) were complexed with the antitumor drug and dicarboxylic acid-terminated polyethylene-glycol (PEG) to form the nanometric complex named DTX-Au-PEG. Following reduction with sodium borohydride (NaBH4), the DTX-Au-PEG complex formed hybrid-metal nanoparticles (DTX IN PEG-AuNPs), where DTX was protected in the gold core embedded within the polymer chains. To achieve therapeutic targeting, DTX-Au-PEG complex and DTX IN PEG-AuNPs were chemical combined with the human anti-EGFR polyclonal antibody, which recognizes the hERG1 channel aberrantly expressed on the membrane of human lung cancer cells. The active targeting was demonstrated by various analytical techniques (Raman and UV-vis spectroscopies); whereas, in vitro experiments on tissue-mimetic, three-dimensional (3D) tumoroids grown at the Air-Liquid Interface (ALI) demonstrated that DTX encapsulation within a gold core strongly influenced the drug efficacy, with a significant increase of the DTX therapeutic index when AuNPs were specifically targeted against EGFR. Collectively, our study demonstrated that a drug delivery system based on Au (III)-DTX complexes constitutes an encouraging chemical approach to build Au (III) complexes into real chemotherapeutic drugs for cancer treatment.
Insights
This study developed novel gold nanoparticles (AuNPs) to improve docetaxel (DTX) delivery for cancer treatment. Targeted AuNPs significantly enhanced DTX efficacy and reduced toxicity in lung cancer models.
Area of Science:
- Nanotechnology in Medicine
- Materials Science
- Oncology
Background:
- Docetaxel (DTX) is a vital anticancer drug, but its clinical use is limited by poor solubility and toxicity.
- Developing advanced drug delivery systems is crucial to enhance DTX efficacy and patient outcomes.
- Gold nanoparticles offer a promising platform for targeted cancer therapy and theranostics.
Purpose of the Study:
- To create a novel drug delivery system using gold complexes for docetaxel (DTX).
- To develop multifunctional, stimuli-responsive nanoplatforms for cancer theranostics.
- To enhance DTX solubility, reduce toxicity, and improve therapeutic targeting in cancer treatment.
Main Methods:
- Complexation of tetrachloroauric acid (HAuCl4) with DTX and polyethylene-glycol (PEG) to form DTX-Au-PEG.
- Reduction to create hybrid-metal nanoparticles (DTX IN PEG-AuNPs) with DTX encapsulated in a gold core.
- Chemical conjugation with anti-EGFR antibodies for targeted delivery to lung cancer cells.
- Validation using Raman and UV-vis spectroscopies, and in vitro studies with 3D tumoroids.
Main Results:
- Successful synthesis of DTX-loaded gold nanoparticles (DTX IN PEG-AuNPs) with enhanced DTX stability.
- Demonstrated active targeting of cancer cells via anti-EGFR antibody conjugation.
- In vitro studies showed significantly increased DTX efficacy and therapeutic index in targeted AuNPs.
- DTX encapsulation within the gold core improved drug performance, especially with EGFR targeting.
Conclusions:
- Gold (III)-docetaxel complexes represent a promising chemical approach for advanced cancer drug delivery.
- The developed AuNP system offers a potential theranostic tool for multifunctional cancer therapy.
- Targeted delivery of DTX via AuNPs enhances therapeutic efficacy and may reduce systemic toxicity.
- This strategy holds potential for improving the clinical application of DTX in treating various malignancies.
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