前药
自愈水凝胶
提拉帕扎明
葡萄糖氧化酶
光动力疗法
肿瘤缺氧
肿瘤微环境
化学
黑色素瘤
缺氧(环境)
癌症研究
癌细胞
化疗
药理学
材料科学
细胞毒性
癌症
放射治疗
生物化学
医学
氧气
酶
有机化学
外科
肿瘤细胞
内科学
体外
作者
Jianhui Zhou,Changcun Liu,Yue Wang,Mengbin Ding,Ningyue Yu,Dongliang Li,Qin Zhang,Jingchao Li
出处
期刊:ACS Biomaterials Science & Engineering
[American Chemical Society]
日期:2022-10-24
卷期号:8 (11): 4886-4895
被引量:6
标识
DOI:10.1021/acsbiomaterials.2c00992
摘要
With the advantages of high safety and selectivity, photodynamic therapy (PDT) has been widely used for cancer treatments, while the anticancer efficacy is often limited because of its relying on oxygen concentrations. Therefore, sole PDT fails to achieve the desired therapeutic effect for hypoxic tumors. To address this issue, we herein report the construction of prodrug and glucose oxidase (GOx) coloaded alginate (ALG) hydrogels for PDT-combined chemotherapy of melanoma. The hydrogels are in situ formed in tumor sites after injection of ALG solution containing semiconducting polymer nanoparticles, hypoxia-responsive prodrug tirapazamine (TPZ), and GOx, which is based on chelation of ALG by endogenous Ca2+. Due to the presence of semiconducting polymer nanoparticles acting as photosensitizers, the hydrogels mediate PDT to produce singlet oxygen (1O2) for directly killing tumor cells, in which oxygen is consumed to create a more hypoxic tumor microenvironment. Moreover, the loaded GOx within hydrogels can deplete oxygen to further aggravate tumor hypoxia. As such, TPZ is effectively activated by hypoxia to cause cancer cell death via chemotherapy. Thus, the hydrogels with laser irradiation achieve a combinational action of PDT with chemotherapy to almost completely eradicate tumors, leading to a much higher therapeutic efficacy relative to sole PDT. This study will provide a promising injectable hydrogel platform for effective treatments of cancer.
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