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PDT-Enhanced Ferroptosis by a Polymer Nanoparticle with pH-Activated Singlet Oxygen Generation and Superb Biocompatibility for Cancer Therapy
Biomacromolecules ( IF 6.2 ) Pub Date : 2021-02-10 , DOI: 10.1021/acs.biomac.0c01679
Jing Li 1 , Junhua Li 2 , Yuji Pu 2 , Sai Li 1 , Wenxia Gao 3 , Bin He 2
Affiliation  

In this study, we reported a nanocomplex (PAF) of PEGylated polygalacturonic acid, 5,10,15,20-tetrakis (4-aminophenyl) porphyrin (TAPP), and Fe3+ for photodynamic therapy (PDT)-enhanced ferroptosis in cancer treatment. PAF exhibited a size of 135 nm and a TAPP and Fe3+ loading content of 6.99 and 0.77%, respectively. The singlet oxygen (1O2) generation capacity of TAPP can be activated and significantly enhanced at acidic pH (4.5–5.0). Besides, the enhanced near-infrared absorption of TAPP at acidic pH enabled a further increase in 1O2 generation capability by a near-infrared laser (760 nm). The polysaccharide-based polymer carrier offers excellent biocompatibility, and PAF displayed a proliferative effect in both normal (L929) and cancer (B16) cells. However, upon light irradiation, PAF exhibited high toxicity to B16 melanoma cells by intracellular reactive oxygen species elevation, glutathione depletion, and lipid peroxidation. PAF displayed a much better anticancer effect than the nanocomplex containing Fe3+ or TAPP alone, indicating the PDT-enhanced ferroptosis in PAF. This study suggested that PDT-enhanced ferroptosis could be a facile and robust strategy of nanotherapeutics with high potency, tumor selectivity, and excellent biocompatibility.

中文翻译:

通过具有pH值活化单线态氧生成和极好的生物相容性的聚合物纳米粒子,PDT增强了肥大症。

在这项研究中,我们报道了聚乙二醇化的聚半乳糖醛酸,5,10,15,20-四(4-氨基苯基)卟啉(TAPP)和Fe 3+的纳米复合物(PAF),用于光动力疗法(PDT)增强了癌症的肥大症治疗。PAF的尺寸为135 nm,TAPP和Fe 3+的负载量分别为6.99和0.77%。TAPP的单线态氧(1 O 2)生成能力可以被激活,并在酸性pH(4.5–5.0)下显着增强。此外,在酸性pH下TAPP的近红外吸收增强,使得1 O 2进一步增加。近红外激光(760 nm)的产生能力。基于多糖的聚合物载体具有出色的生物相容性,PAF在正常(L929)和癌细胞(B16)中均显示出增殖作用。然而,在光照射下,PAF通过细胞内反应性氧的升高,谷胱甘肽耗竭和脂质过氧化对B16黑色素瘤细胞表现出高毒性。与仅含有Fe 3+或TAPP的纳米复合物相比,PAF表现出更好的抗癌作用,表明PAF中PDT增强了肥大症。这项研究表明,PDT增强的肥大症可能是一种纳米治疗剂的简便而稳健的策略,具有很高的效力,肿瘤选择性和出色的生物相容性。
更新日期:2021-03-08
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