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One-Step Aqueous Synthesis of Anionic and Cationic AgInS2 Quantum Dots and Their Utility in Improving the Efficacy of ALA-Based Photodynamic Therapy

Hashemkhani, M; Loizidou, M; MacRobert, AJ; Yagci Acar, H; (2022) One-Step Aqueous Synthesis of Anionic and Cationic AgInS2 Quantum Dots and Their Utility in Improving the Efficacy of ALA-Based Photodynamic Therapy. Inorganic Chemistry , 61 (6) pp. 2846-2863. 10.1021/acs.inorgchem.1c03298. Green open access

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Abstract

Silver–indium–sulfide quantum dots (AIS QDs) have potential applications in many areas, including biomedicine. Their lack of regulated heavy metals, unlike many commercialized QDs, stands out as an advantage, but the necessity for alloyed or core–shell structures and related costly and sophisticated processes for the production of stable and high quantum yield aqueous AIS QDs are the current challenges. The present study demonstrates the one-step aqueous synthesis of simple AgInS2 QD compositions utilizing for the first time either a polyethyleneimine/2-mercaptopropionic acid (AIS-PEI/2MPA) mixture or only 2-mercaptopropionic acid (AIS-2MPA) as the stabilizing molecules, providing a AgInS2 portfolio consisting of cationic and anionic AIS QDs, respectively, and tuneable emission. Small AIS QDs with long-term stability and high quantum yields (19–23%) were achieved at a molar ratio of Ag/In/S 1/10/10 in water without any dopant or a semiconductor shell. The theranostic potential of these cationic and anionic AIS QDs was also evaluated in vitro. Non-toxic doses were determined, and fluorescence imaging potential was demonstrated. More importantly, these QDs were electrostatically loaded with zwitterionic 5-aminolevulinic acid (ALA) as a prodrug to enhance the tumor availability of ALA and to improve ALA-induced porphyrin photodynamic therapy (PDT). This is the first study investigating the influence of nanoparticle charge on ALA binding, release, and therapeutic efficacy. Surface charge was found to be more critical in cellular internalization and dark toxicity rather than drug loading and release. Both QDs provided enhanced ALA release at acidic pH but protected the prodrug at physiological pH, which is critical for tumor delivery of ALA, which suffers from low bioavailability. The PDT efficacy of the ALA-loaded AIS QDs was tested in 2D monolayers and 3D constructs of HT29 and SW480 human colon adenocarcinoma cancer cell lines. The incorporation of ALA delivery by the AIS QDs, which on their own do not cause phototoxicity, elicited significant cell death due to enhanced light-induced ROS generation and apoptotic/necrotic cell death, reducing the IC50 for ALA dramatically to about 0.1 and 0.01 mM in anionic and cationic AIS QDs, respectively. Combined with simple synthetic methods, the strong intracellular photoluminescence of AIS QDs, good biocompatibility of especially the anionic AIS QDs, and the ability to act as drug carriers for effective PDT signify that the AIS QDs, in particular AIS-2MPA, are highly promising theranostic QDs.

Type: Article
Title: One-Step Aqueous Synthesis of Anionic and Cationic AgInS2 Quantum Dots and Their Utility in Improving the Efficacy of ALA-Based Photodynamic Therapy
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1021/acs.inorgchem.1c03298
Publisher version: https://doi.org/10.1021/acs.inorgchem.1c03298
Language: English
Additional information: This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Tumor Cells, Cultured, Humans, Anions, Sulfides, Cations, Indium, Silver, Water, Aminolevulinic Acid, Antineoplastic Agents, Photosensitizing Agents, Photochemotherapy, Drug Screening Assays, Antitumor, Quantum Dots, Cell Proliferation, Cell Survival, Optical Imaging
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Surgical Biotechnology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
URI: https://discovery.ucl.ac.uk/id/eprint/10144654
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