Department of Biomedical Sciences, City University of Hong Kong , Tat Chee Avenue, Kowloon, Hong Kong, China.
ACS Appl Mater Interfaces. 2017 Jul 19;9(28):23487-23496. doi: 10.1021/acsami.7b06353. Epub 2017 Jul 6.
An acid-cleavable acetal-linked zinc(II) phthalocyanine dimer with an azido terminal group (cPc) was prepared and conjugated to alkyne-modified mesoporous silica nanoparticles via copper(I)-catalyzed alkyne-azide cycloaddition reaction. For comparison, an amine-linked analogue (nPc) was also prepared as a non-acid-cleavable counterpart. These dimeric phthalocyanines were significantly self-quenched due to the close proximity of the phthalocyanine units inside the mesopores, resulting in much weaker fluorescence emission and singlet oxygen generation, both in N,N-dimethylformamide and in phosphate-buffered saline (PBS), compared with the free molecular counterparts. Under acidic conditions in PBS, the cPc-encapsulated nanosystem was activated in terms of fluorescence emission and singlet oxygen production. After internalization into human colon adenocarcinoma HT29 cells, it exhibited much higher intracellular fluorescence and photocytotoxicity compared to the nanosystem entrapped with nPc. The activation of this nanosystem was also demonstrated in tumor-bearing nude mice. The intratumoral fluorescence intensity increased gradually over 24 h, while for the nPc counterpart the fluorescence remained very weak. The results suggest that this nanosystem serves as a promising activatable nanophotosensitizing agent for photodynamic therapy.
一种具有叠氮端基的酸可裂解缩醛连接的锌(II)酞菁二聚体（cPc）被制备出来，并通过铜（I）催化的炔烃-叠氮环加成反应与炔烃修饰的介孔硅纳米粒子连接。为了进行比较，还制备了一种胺连接的类似物（nPc）作为非酸可裂解的对照物。这些二聚酞菁由于介孔内酞菁单元的紧密接近而显著自猝灭，导致在 N，N-二甲基甲酰胺和磷酸盐缓冲盐水（PBS）中荧光发射和单线态氧生成都比游离分子对应物弱得多。在 PBS 中的酸性条件下，cPc 封装的纳米系统在荧光发射和单线态氧生成方面被激活。在被内化进入人结肠腺癌 HT29 细胞后，与封装 nPc 的纳米系统相比，其细胞内荧光强度和光毒性显著提高。在荷瘤裸鼠中也证明了这种纳米系统的激活。肿瘤内荧光强度在 24 小时内逐渐增加，而 nPc 对应的荧光仍然很弱。这些结果表明，该纳米系统是一种有前途的可激活的光动力治疗光敏剂。
