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与两性霉素B共轭的胺功能化石墨烯量子点:用于内脏利什曼病治疗的合成、表征及体外评价

Amine-Functionalized Graphene Quantum Dots Conjugated with Amphotericin B: Synthesis, Characterization, and In Vitro Evaluation for Visceral Leishmaniasis Treatment.

作者信息

Madhukar Prasoon, Kesarwani Rashmi, Pandey Sundaram, Singh Vishal Kumar, Rao Gedda Mallikarjuna, Singh Om Prakash, Shaz Mohammad, Kumar Rajiv, Sundar Shyam

机构信息

Infectious Diseases Research Laboratory, Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh 221005, India.

Hydrogen Energy Centre, Department of Physics, Institute of Science, Banaras Hindu University, Varanasi, Uttar Pradesh 221005, India.

出版信息

ACS Omega. 2025 Jun 17;10(25):26627-26638. doi: 10.1021/acsomega.5c00879. eCollection 2025 Jul 1.


DOI:10.1021/acsomega.5c00879
PMID:40620982
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12223831/
Abstract

Visceral Leishmaniasis (VL) is a life-threatening parasitic disease primarily affecting populations in resource-limited, endemic regions. Existing treatments for VL face limitations such as toxicity, high costs, and suboptimal efficacy in specific patient groups. Given the lack of a vaccine, chemotherapy remains the only option, emphasizing the urgent need for safer and more effective treatments. Nanotechnology offers promising avenues to overcome these challenges. This study introduces a novel approach involving amine-functionalized graphene quantum dots (fGQDs) conjugated with Amphotericin B (fGQDAmB) to enhance targeted drug delivery to -infected macrophages. This novel approach, which could lead to a safer and more effective treatment for VL, is a significant contribution to the field. Structural characterization by XRD and FTIR confirmed successful GQD synthesis and functionalization, while cellular assays demonstrated significantly higher macrophage uptake and enhanced antileishmanial efficacy. fGQDAmB demonstrated approximately 4.2-fold greater potency against intracellular amastigotes and 2-fold higher efficacy against promastigotes, while also exhibiting reduced cytotoxicity compared to conventional AmB. The safety and effectiveness of fGQDAmB were further validated through hemolysis assay, providing reassurance and confidence about its potential use and instilling confidence in the potential of Quantum Dot-based Nanomedicine formulations.

摘要

内脏利什曼病(VL)是一种危及生命的寄生虫病,主要影响资源有限的流行地区的人群。现有的VL治疗方法面临毒性、高成本以及在特定患者群体中疗效欠佳等局限性。由于缺乏疫苗,化疗仍然是唯一的选择,这凸显了对更安全、更有效治疗方法的迫切需求。纳米技术为克服这些挑战提供了有前景的途径。本研究引入了一种新方法,即将胺功能化的石墨烯量子点(fGQDs)与两性霉素B(fGQDAmB)共轭,以增强对感染巨噬细胞的靶向药物递送。这种新方法可能会带来一种更安全、更有效的VL治疗方法,是该领域的一项重大贡献。通过XRD和FTIR进行的结构表征证实了GQD的成功合成和功能化,而细胞试验表明巨噬细胞摄取显著增加且抗利什曼原虫疗效增强。fGQDAmB对细胞内无鞭毛体的效力约高4.2倍,对前鞭毛体的疗效高2倍,同时与传统两性霉素B相比,其细胞毒性降低。通过溶血试验进一步验证了fGQDAmB的安全性和有效性,为其潜在用途提供了保证和信心,并使人对基于量子点的纳米药物制剂的潜力充满信心。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2637/12223831/fc8844a4dcd9/ao5c00879_0015.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2637/12223831/174dee122b39/ao5c00879_0002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2637/12223831/fc8844a4dcd9/ao5c00879_0015.jpg

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本文引用的文献

[1]
Conjugates of amphotericin B to resolve challenges associated with its delivery.

Expert Opin Drug Deliv. 2024-2

[2]
Tuning sterol extraction kinetics yields a renal-sparing polyene antifungal.

Nature. 2023-11

[3]
Liposomal Amphotericin B for Treatment of Leishmaniasis: From the Identification of Critical Physicochemical Attributes to the Design of Effective Topical and Oral Formulations.

Pharmaceutics. 2022-12-28

[4]
Amphotericin B assembles into seven-molecule ion channels: An NMR and molecular dynamics study.

Sci Adv. 2022-6-17

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Formulation of Amphotericin B in PEGylated Liposomes for Improved Treatment of Cutaneous Leishmaniasis by Parenteral and Oral Routes.

Pharmaceutics. 2022-5-5

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Covalent Conjugation of Amphotericin B to Hyaluronic Acid: An Injectable Water-Soluble Conjugate with Reduced Toxicity and Anti-Leishmanial Potential.

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Evaluation of Safety and Antileishmanial Efficacy of Amine Functionalized Carbon-Based Composite Nanoparticle Appended With Amphotericin B: An and Preclinical Study.

Front Chem. 2020-7-3

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