Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, School of Pharmaceutical Sciences, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, 310053, People's Republic of China.
Int J Nanomedicine. 2024 Sep 28;19:9973-9987. doi: 10.2147/IJN.S473052. eCollection 2024.
Breast cancer ranks among the most prevalent cancers in women, characterized by significant morbidity, disability, and mortality. Presently, chemotherapy is the principal clinical approach for treating breast cancer; however, it is constrained by limited targeting capability and an inadequate therapeutic index. Photothermal therapy, as a non-invasive approach, offers the potential to be combined with chemotherapy to improve tumor cellular uptake and tissue penetration. In this research, a mesoporous polydopamine-coated gold nanorod nanoplatform, encapsulating doxorubicin (Au@mPDA@DOX), was developed.
This nanoplatform was constructed by surface coating mesoporous polydopamine (mPDA) onto gold nanorods, and doxorubicin (DOX) was encapsulated in Au@mPDA owing to π-π stacking between mPDA and DOX. The dynamic diameter, zeta potential, absorbance, photothermal conversion ability, and drug release behavior were determined. The cellular uptake, cytotoxicity, deep penetration, and anti-tumor effects were subsequently investigated in 4T1 cells. After that, fluorescence imaging, photothermal imaging and pharmacodynamics studies were utilized to evaluate the anti-tumor effects in tumor-bearing mice model.
This nanoplatform exhibited high drug loading capacity, excellent photothermal conversion and, importantly, pH/photothermal dual-responsive drug release behavior. The in vitro results revealed enhanced photothermal-facilitated cellular uptake, drug release and tumor penetration of Au@mPDA@DOX under near-infrared irradiation. In vivo studies confirmed that, compared with monotherapy with either chemotherapy or photothermal therapy, the anti-tumor effects of Au@mPDA@DOX are synergistically improved.
Together with good biosafety and biocompatibility, the Au@mPDA@DOX nanoplatform provides an alternative method for safe and synergistic treatment of breast cancer.
乳腺癌是女性中最常见的癌症之一,其特点是发病率高、致残率高和死亡率高。目前,化疗是治疗乳腺癌的主要临床方法;然而,它受到靶向能力有限和治疗指数不足的限制。光热疗法作为一种非侵入性方法,有可能与化疗相结合,以提高肿瘤细胞摄取和组织穿透性。在这项研究中,开发了一种介孔聚多巴胺包覆的金纳米棒纳米平台,包裹阿霉素(Au@mPDA@DOX)。
该纳米平台通过在金纳米棒表面包覆介孔聚多巴胺(mPDA)构建而成,由于 mPDA 和 DOX 之间的π-π堆积,阿霉素(DOX)被包裹在 Au@mPDA 中。测定了动态直径、zeta 电位、吸光度、光热转换能力和药物释放行为。随后在 4T1 细胞中研究了细胞摄取、细胞毒性、深层渗透和抗肿瘤作用。之后,利用荧光成像、光热成像和药效学研究来评估荷瘤小鼠模型中的抗肿瘤效果。
该纳米平台具有高载药能力、优异的光热转换能力,重要的是具有 pH/光热双重响应的药物释放行为。体外结果表明,在近红外照射下,Au@mPDA@DOX 增强了光热辅助细胞摄取、药物释放和肿瘤渗透。体内研究证实,与单独化疗或光热治疗相比,Au@mPDA@DOX 的抗肿瘤效果得到协同改善。
Au@mPDA@DOX 纳米平台具有良好的生物安全性和生物相容性,为安全协同治疗乳腺癌提供了一种替代方法。