Li Bei, Fu Yi, Xie Maodi, Feng Lei, Niu Xiaoya, Que Lin, You Zhen
Division of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China.
Research Center for Biliary Diseases, West China Hospital, Sichuan University, Chengdu, China.
Front Bioeng Biotechnol. 2022 Aug 17;10:957349. doi: 10.3389/fbioe.2022.957349. eCollection 2022.
In order to solve the different pains caused by traditional cancer treatment methods such as surgical treatment, the nano-drug delivery system provides new ideas for cancer treatment. In this paper, a novel anti-tumor therapy nanoparticle, P(AAm-co-AN)-AuNRs@CeO-Ce6(PA/Ce6), is prepared, which provides a novel idea for liver cancer treatment. The CeO-coated gold nanorods were grafted onto the surface of the temperature-sensitive polymer P(AAm-co-AN)-CTPD. The photosensitizer Ce6 is loaded on the surface of the nanoparticles and the polymer layer. CeO can effectively alleviate the tumor anaerobic microenvironment, and under 808 nm near-infrared (NIR) excitation, the gold nanorods achieve photothermal conversion to induce local heating, which leads to the phase transition of the polymer layer and realizes a controllable release mechanism. In addition, 660 nm NIR light can effectively induce Ce6 to produce singlet oxygen, thereby effectively killing cancer cells. Under the 808 nm laser irradiation within 600 s, the PA/Ce6 solution can heat up to about 60°C, which was enough to ablate both cancer cells and tumor tissues. When the temperature was 50°C, the cumulative release rate of Ce6 was 95.31%. Under the 808 nm laser irradiation, oxygen production capacity of PA/Ce6 was higher and can effectively reduce the content of hydrogen peroxide in cancer cells. Compared to free Ce6, the reactive oxygen species-mediated fluorescence of PA/Ce6 nanoparticles was greater. The cell viability and migration of HepG2 cells were decreased after the 660 and 880 nm lasers were irradiated at the same time. The cancer cells were further inhibited, showing a good anti-tumor effect. PA-DOX showed the best tumor growth inhibitory effect under NIR laser irradiation and had no acute toxicity . Due to the existence of AuNRs, nanoparticles had high-efficiency photothermal conversion ability to achieve photothermal therapy. Ce6 can generate singlet oxygen under the excitation of 660 nm laser to realize photodynamic therapy. The experimental results also showed that PA/Ce6 can effectively decompose hydrogen peroxide under laser irradiation, aiming to effectively alleviate the anaerobic microenvironment of tumors. These indicate that PA/Ce6 plays a promising role for hepatocellular carcinoma treatment.
为了解决手术治疗等传统癌症治疗方法所带来的不同疼痛，纳米药物递送系统为癌症治疗提供了新思路。本文制备了一种新型抗肿瘤治疗纳米粒子P(AAm-co-AN)-AuNRs@CeO-Ce6(PA/Ce6)，为肝癌治疗提供了新的思路。将CeO包覆的金纳米棒接枝到温敏聚合物P(AAm-co-AN)-CTPD表面。光敏剂Ce6负载在纳米粒子表面和聚合物层上。CeO能有效缓解肿瘤缺氧微环境，在808 nm近红外(NIR)激发下，金纳米棒实现光热转换以诱导局部加热，从而导致聚合物层的相变并实现可控释放机制。此外，660 nm近红外光可有效诱导Ce6产生单线态氧，从而有效杀死癌细胞。在808 nm激光照射600 s内，PA/Ce6溶液可升温至约60°C，足以消融癌细胞和肿瘤组织。当温度为50°C时，Ce6的累积释放率为95.31%。在808 nm激光照射下，PA/Ce6的产氧能力更高，能有效降低癌细胞中过氧化氢的含量。与游离Ce6相比，PA/Ce6纳米粒子的活性氧介导的荧光更强。同时用660和880 nm激光照射后，HepG2细胞的细胞活力和迁移能力降低。癌细胞进一步受到抑制，显示出良好的抗肿瘤效果。PA-DOX在近红外激光照射下显示出最佳的肿瘤生长抑制效果且无急性毒性。由于AuNRs的存在，纳米粒子具有高效的光热转换能力以实现光热治疗。Ce6在660 nm激光激发下可产生单线态氧以实现光动力治疗。实验结果还表明，PA/Ce6在激光照射下可有效分解过氧化氢，旨在有效缓解肿瘤的缺氧微环境。这些表明PA/Ce6在肝细胞癌治疗中具有广阔的应用前景。
