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可生物降解的锰掺杂羟基磷灰石抗肿瘤佐剂作为一种有前景的癌症光疗药物。

Biodegradable manganese-doped hydroxyapatite antitumor adjuvant as a promising photo-therapeutic for cancer treatment.

作者信息

Park Sumin, Choi Jaeyeop, Doan Vu Hoang Minh, O Se Hwi

机构信息

Industry 4.0 Convergence Bionics Engineering, Pukyong National University, Busan, South Korea.

Smart Gym-Based Translational Research Center for Active Senior's Healthcare, Pukyong National University, Busan, South Korea.

出版信息

Front Mol Biosci. 2022 Nov 23;9:1085458. doi: 10.3389/fmolb.2022.1085458. eCollection 2022.

Abstract

The efficiency of a cancer therapy agent depends on its ability to eliminate tumors without endangering neighboring healthy tissues. In this present study, a novel multifunctional property enriched nanostructured system was synthesized on manganese-doped hydroxyapatite (Mn-HAp) conjugated with counter folic acid (FA) IR-783 fluorescence dye. The tailored synthesis of nano rod-shaped Mn-HAp nanoparticles with high surface area allows to conjugate FA/IR-783 dye which enhanced retention time during circulation. The drug-free Photothermal Photodynamic therapy mediated cancer treatment permits the prevention of collateral damages to non-cancerous cells. The safe HAp biomaterial matrix allows a large number of molecules on its surface due to its active different charge moieties (Ca/PO ) without any recurrence toxicity. The doped Mn allows releasing of Mn ions which triggered the production of toxic hydroxyl radicals (•OH) Fenton or Fenton-like reactions to decompose HO in the tumor sites. Herein, IR-783 and FA were selected for targeted fluorescence imaging-guided photothermal therapy. 6The PTT performance of synthesized nanostructured system shows enhanced potential with ∼60°C temperature elevation with 0.75 W∙cm power irradiated within 7 min of treatment. PDT activity was also observed initially with Methylene Blue (MB) as a targeted material which shows a drastic degradation of MB and further studies with MDA-MB-231 breast cancer cell line show cytotoxicity due to the generated reactive oxygen species (ROS) effect. FA/IR-783 conjugated Mn-HAp nanoparticles (2.0 mol% Mn-HAp/FA-IR-783) show significant tumor-specific targeting and treatment efficiency while intravenously injected in (tail vain) BALB/c nude mice model without any recurrence. The synthesized nanostructured system had ample scope to be a promising Photo-Therapeutic agent for cancer treatment.

摘要

癌症治疗药物的疗效取决于其在不危及邻近健康组织的情况下消除肿瘤的能力。在本研究中,在与叶酸(FA)-IR-783荧光染料共轭的锰掺杂羟基磷灰石(Mn-HAp)上合成了一种具有新型多功能特性的富集纳米结构系统。具有高表面积的纳米棒状Mn-HAp纳米颗粒的定制合成使得能够共轭FA/IR-783染料,从而延长了其在循环过程中的保留时间。无药物的光热光动力疗法介导的癌症治疗可防止对非癌细胞的附带损害。安全的HAp生物材料基质由于其活性不同的电荷部分(Ca/PO),允许在其表面存在大量分子,且无任何复发毒性。掺杂的Mn允许释放Mn离子,这些离子通过Fenton或类Fenton反应触发有毒羟基自由基(•OH)的产生,从而在肿瘤部位分解H₂O₂。在此,选择IR-783和FA用于靶向荧光成像引导的光热疗法。合成的纳米结构系统的光热疗法性能显示出增强的潜力,在7分钟的治疗时间内,以0.75 W∙cm²的功率照射可使温度升高约60°C。最初还观察到以亚甲基蓝(MB)作为靶向材料的光动力疗法活性,这表明MB有剧烈降解,并且对MDA-MB-231乳腺癌细胞系的进一步研究表明,由于产生的活性氧(ROS)效应具有细胞毒性。当静脉注射到(尾静脉)BALB/c裸鼠模型中时,FA/IR-783共轭的Mn-HAp纳米颗粒(2.0 mol% Mn-HAp/FA-IR-783)显示出显著的肿瘤特异性靶向和治疗效率,且无任何复发。合成的纳米结构系统有很大的潜力成为一种有前景的用于癌症治疗的光治疗剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41fc/9726924/e52727ee2837/fmolb-09-1085458-g001.jpg

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