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聚乙烯亚胺/金纳米棒与碳量子点和透明质酸共轭用于乳腺癌的化学-光热疗法

Polyethyleneimine/gold nanorods conjugated with carbon quantum dots and hyaluronic acid for chemo-photothermal therapy of breast cancer.

作者信息

Khoshnood Ali, Farhadian Nafiseh, Abnous Khalil, Matin Maryam M, Ziaee Nasrin, Iranpour Sonia

机构信息

Chemical Engineering Department, Faculty of Engineering, Ferdowsi University of Mashhad, Mashhad, Iran.

Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

J Mater Chem B. 2025 Apr 16;13(16):4893-4909. doi: 10.1039/d4tb02234c.

Abstract

The aim of this study was to develop a stable polyethyleneimine/gold nanorod composite conjugated with a carbon quantum dot (CQD) and hyaluronic acid (HA) complex (CQD-HA-PEI@GNRs) for applications in chemotherapy and photothermal therapy. GNRs were synthesized using a seed-mediated growth method, and the amount of seed solution was optimized to obtain GNRs with an optimal aspect ratio and a strong peak in the near-infrared (NIR) region. The surface of the GNRs was then modified with polyethylene imine (PEI). In parallel, CQDs were synthesized through a hydrothermal method and subsequently conjugated with HA to act as an active targeting ligand. The resulting CQD-HA complex was loaded onto the surface of the PEI@GNR composite. Finally, the anticancer drug doxorubicin (DOX) was effectively loaded onto this innovative complex. The cytotoxicity of the final complex was evaluated on different cell lines in the presence and absence of laser irradiation. Furthermore, the efficacy of the formulation was investigated in BALB/c mice bearing breast cancer tumors. Characterization results confirmed the successful formation of GNRs with a length of 40 nm, exhibiting a strong peak at 813 nm in the NIR region. The zeta potential value of the GNRs was -25.62 mV, which increased to +40.59 mV after the surface modification with PEI. CQDs were synthesized and successfully conjugated with HA. DOX encapsulation efficiency was 92.8%, with appropriate drug release profiles in the presence of laser irradiation. The final complex showed appropriate cytotoxicity toward 4T1 and MCF7 breast cancer cell lines. analysis of the CQD-HA-PEI@GNR-DOX complex combined with laser treatment demonstrated significant tumor growth inhibition in comparison to the control group. Finally, this novel complex was proposed as an alternative for breast cancer treatment.

摘要

本研究的目的是开发一种稳定的聚乙烯亚胺/金纳米棒复合材料,其与碳量子点(CQD)和透明质酸(HA)复合物(CQD-HA-PEI@GNRs)共轭,用于化疗和光热治疗。采用种子介导生长法合成金纳米棒,并优化种子溶液的用量,以获得具有最佳纵横比和近红外(NIR)区域强峰的金纳米棒。然后用聚乙烯亚胺(PEI)修饰金纳米棒的表面。同时,通过水热法合成碳量子点,随后将其与透明质酸共轭,作为活性靶向配体。将所得的CQD-HA复合物负载到PEI@GNR复合材料的表面。最后,将抗癌药物阿霉素(DOX)有效负载到这种创新复合物上。在有和没有激光照射的情况下,评估最终复合物对不同细胞系的细胞毒性。此外,在携带乳腺癌肿瘤的BALB/c小鼠中研究了该制剂的疗效。表征结果证实成功形成了长度为40nm的金纳米棒,在近红外区域813nm处呈现强峰。金纳米棒的zeta电位值为-25.62mV,用PEI进行表面修饰后增加到+40.59mV。合成了碳量子点并成功与透明质酸共轭。DOX包封效率为92.8%,在激光照射下具有适当的药物释放曲线。最终复合物对4T1和MCF7乳腺癌细胞系表现出适当的细胞毒性。与对照组相比,对CQD-HA-PEI@GNR-DOX复合物与激光治疗相结合的分析表明肿瘤生长受到显著抑制。最后,提出这种新型复合物可作为乳腺癌治疗的替代方案。

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