Institute for Solar Energy Systems, C501, School of Engineering, Sun Yat-sen University, Higher Education Mega Center, Panyu District, Guangzhou 510006, China; Department of Otolaryngology Head and Neck Surgery, Zhuhai People's Hospital, Zhuhai, 519000, Guangdong, China.
Department of Otolaryngology Head and Neck Surgery, Zhuhai People's Hospital, Zhuhai, 519000, Guangdong, China; Department of Otolaryngology-Head and Neck Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, Guangdong, China.
Biochem Biophys Res Commun. 2021 Jun 11;557:240-246. doi: 10.1016/j.bbrc.2021.03.168. Epub 2021 Apr 21.
Platinum-based concurrent chemo-radiotherapy is the most common strategy for the treatment of Nasopharyngeal carcinoma. However, low efficacy and side effects are the two major problems associated with this approach. Therefore, it is urgent need to explore novel therapeutic modalities to meet clinically standards. Photothermal therapy (PTT) and photodynamic therapy (PDT) are non-invasive and light trigger modalities received great attention to overcome the limitations and significantly improved cancer therapy. Here, we developed acidity surface charge transformable nanocluster (NCs) composed of Indocyanine green (ICG), FeO, and Palmitoyl ascorbic acid (PA) with pH-responsive PEG-b-PAEMA-PDMA for enhanced synergistic PDT/PTT. NCs has the neutral hydrophilic surface helps to prolong blood circulation and instantly transformed to positively charged surface at tumoral acidic pH (6.5), which promoted the cellular uptake. Under laser irradiation (808 nm, 1 W/cm), NCs produced PTT effect, concurrently it converts singlet oxygen (O) into HO, which can be further involved in Fenton reaction and produce toxic hydroxyl radical (•OH) enhances therapy efficacy. In vitro experiments on HNE-1 cancer cells showed improved intracellular uptake of NCs at low pH and simultaneously induced higher cytotoxicity medicated by synergetic PDT/PTT effect. In vivo therapeutic study revealed that NCs treatment under laser irradiation showed superior inhibition of tumor growth in HNE-1 tumor bearing mice model. Taken together, the present findings suggest that NCs could be used as "all in one" nano theranostic agent for enhanced PDT/PTT of cancer therapy.
基于铂的同期放化疗是治疗鼻咽癌最常用的策略。然而,低疗效和副作用是该方法面临的两个主要问题。因此,迫切需要探索新的治疗方式来满足临床标准。光热疗法(PTT)和光动力疗法(PDT)是无创的、光触发的治疗方式,受到了极大的关注,以克服限制并显著改善癌症治疗。在这里,我们开发了由吲哚菁绿(ICG)、FeO 和棕榈酰抗坏血酸(PA)组成的酸度表面电荷可转换纳米团簇(NCs),并带有 pH 响应的聚乙二醇-b-PAEMA-PDMA,以增强协同 PDT/PTT。NCs 的中性亲水表面有助于延长血液循环,在肿瘤酸性 pH(6.5)下瞬间转变为带正电荷的表面,从而促进细胞摄取。在激光照射(808nm,1W/cm)下,NCs 产生 PTT 效应,同时将单线态氧(O)转化为 HO,HO 可以进一步参与芬顿反应并产生有毒的羟基自由基(•OH),增强治疗效果。在 HNE-1 癌细胞的体外实验中,在低 pH 下,NCs 的细胞内摄取得到改善,同时协同 PDT/PTT 效应诱导更高的细胞毒性。体内治疗研究表明,激光照射下 NCs 的治疗在 HNE-1 荷瘤小鼠模型中表现出优异的肿瘤生长抑制作用。总之,这些发现表明,NCs 可用作“一体化”纳米治疗剂,以增强癌症的 PDT/PTT 治疗。