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pH-Responsive Upconversion Mesoporous Silica Nanospheres for Combined Multimodal Diagnostic Imaging and Targeted Photodynamic and Photothermal Cancer Therapy
ACS Nano ( IF 15.8 ) Pub Date : 2023-09-13 , DOI: 10.1021/acsnano.3c04564
L Palanikumar 1 , Mona Kalmouni 1 , Tatiana Houhou 1 , Osama Abdullah 2 , Liaqat Ali 2 , Renu Pasricha 2 , Rainer Straubinger 2 , Sneha Thomas 2 , Ahmed Jawaad Afzal 1 , Francisco N Barrera 3 , Mazin Magzoub 1
ACS Nano ( IF 15.8 ) Pub Date : 2023-09-13 , DOI: 10.1021/acsnano.3c04564
L Palanikumar 1 , Mona Kalmouni 1 , Tatiana Houhou 1 , Osama Abdullah 2 , Liaqat Ali 2 , Renu Pasricha 2 , Rainer Straubinger 2 , Sneha Thomas 2 , Ahmed Jawaad Afzal 1 , Francisco N Barrera 3 , Mazin Magzoub 1
Affiliation
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Photodynamic therapy (PDT) and photothermal therapy (PTT) have gained considerable attention as potential alternatives to conventional cancer treatments. However, these approaches remain limited by low solubility, poor stability, and inefficient targeting of many common photosensitizers (PSs) and photothermal agents (PTAs). To overcome the aforementioned limitations, we engineered biocompatible and biodegradable tumor-targeted upconversion nanospheres with imaging capabilities. The multifunctional nanospheres consist of a sodium yttrium fluoride core doped with lanthanides (ytterbium, erbium, and gadolinium) and the PTA bismuth selenide (NaYF4:Yb/Er/Gd,Bi2Se3) enveloped in a mesoporous silica shell that encapsulates a PS, chlorin e6 (Ce6), within its pores. NaYF4:Yb/Er converts deeply penetrating near-infrared (NIR) light to visible light, which excites Ce6 to generate cytotoxic reactive oxygen species (ROS), while Bi2Se3 efficiently converts absorbed NIR light to heat. Additionally, Gd enables magnetic resonance imaging of the nanospheres. The mesoporous silica shell is coated with DPPC/cholesterol/DSPE-PEG to retain the encapsulated Ce6 and prevent serum protein adsorption and macrophage recognition that hinder tumor targeting. Finally, the coat is conjugated to the acidity-triggered rational membrane (ATRAM) peptide, which promotes specific and efficient internalization into malignant cells in the mildly acidic microenvironment of tumors. The nanospheres facilitated tumor magnetic resonance and thermal and fluorescence imaging and exhibited potent NIR laser light-induced anticancer effects in vitro and in vivo via combined ROS production and localized hyperthermia, with negligible toxicity to healthy tissue, hence markedly extending survival. Our results demonstrate that the ATRAM-functionalized, lipid/PEG-coated upconversion mesoporous silica nanospheres (ALUMSNs) offer multimodal diagnostic imaging and targeted combinatorial cancer therapy.
中文翻译:
pH 响应上转换介孔二氧化硅纳米球用于组合多模式诊断成像和靶向光动力和光热癌症治疗
光动力疗法(PDT)和光热疗法(PTT)作为传统癌症治疗的潜在替代方案已获得相当多的关注。然而,这些方法仍然受到许多常见光敏剂(PS)和光热剂(PTA)溶解度低、稳定性差和靶向效率低的限制。为了克服上述限制,我们设计了具有成像功能的生物相容性和可生物降解的肿瘤靶向上转换纳米球。多功能纳米球由掺杂有镧系元素(镱、铒和钆)的氟化钇钠核和包裹在介孔二氧化硅壳中的PTA 硒化铋 (NaYF 4 :Yb/Er/Gd,Bi 2 Se 3 ) 组成。 PS,二氢卟酚 e6 (Ce6),位于其孔隙内。NaYF 4 :Yb/Er 将深度穿透的近红外 (NIR) 光转化为可见光,从而激发 Ce6 产生细胞毒性活性氧 (ROS),而 Bi 2 Se 3 有效地将吸收的近红外光转化为热量。此外,Gd 可以对纳米球进行磁共振成像。介孔二氧化硅外壳涂有DPPC/胆固醇/DSPE-PEG,以保留封装的Ce6并防止阻碍肿瘤靶向的血清蛋白吸附和巨噬细胞识别。最后,该涂层与酸度触发的理性膜(ATRAM)肽缀合,促进肿瘤弱酸性微环境中的恶性细胞特异性、高效的内化。纳米球促进肿瘤磁共振以及热和荧光成像,并通过结合ROS产生和局部热疗在体外和体内表现出有效的近红外激光诱导的抗癌作用,对健康组织的毒性可以忽略不计,从而显着延长生存期。我们的结果表明,ATRAM 功能化、脂质/PEG 涂层的上转换介孔二氧化硅纳米球 (ALUMSN) 提供多模式诊断成像和靶向组合癌症治疗。
更新日期:2023-09-13
中文翻译:
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pH 响应上转换介孔二氧化硅纳米球用于组合多模式诊断成像和靶向光动力和光热癌症治疗
光动力疗法(PDT)和光热疗法(PTT)作为传统癌症治疗的潜在替代方案已获得相当多的关注。然而,这些方法仍然受到许多常见光敏剂(PS)和光热剂(PTA)溶解度低、稳定性差和靶向效率低的限制。为了克服上述限制,我们设计了具有成像功能的生物相容性和可生物降解的肿瘤靶向上转换纳米球。多功能纳米球由掺杂有镧系元素(镱、铒和钆)的氟化钇钠核和包裹在介孔二氧化硅壳中的PTA 硒化铋 (NaYF 4 :Yb/Er/Gd,Bi 2 Se 3 ) 组成。 PS,二氢卟酚 e6 (Ce6),位于其孔隙内。NaYF 4 :Yb/Er 将深度穿透的近红外 (NIR) 光转化为可见光,从而激发 Ce6 产生细胞毒性活性氧 (ROS),而 Bi 2 Se 3 有效地将吸收的近红外光转化为热量。此外,Gd 可以对纳米球进行磁共振成像。介孔二氧化硅外壳涂有DPPC/胆固醇/DSPE-PEG,以保留封装的Ce6并防止阻碍肿瘤靶向的血清蛋白吸附和巨噬细胞识别。最后,该涂层与酸度触发的理性膜(ATRAM)肽缀合,促进肿瘤弱酸性微环境中的恶性细胞特异性、高效的内化。纳米球促进肿瘤磁共振以及热和荧光成像,并通过结合ROS产生和局部热疗在体外和体内表现出有效的近红外激光诱导的抗癌作用,对健康组织的毒性可以忽略不计,从而显着延长生存期。我们的结果表明,ATRAM 功能化、脂质/PEG 涂层的上转换介孔二氧化硅纳米球 (ALUMSN) 提供多模式诊断成像和靶向组合癌症治疗。