Drug induced mitochondria dysfunction to enhance photodynamic therapy of hypoxic tumors

被引：10

作者：

Cen, Yi ^{[1
,2
]}

Chen, Xiayun ^{[1
,2
]}

Liu, Yibin ^{[1
,2
]}

Yu, Baixue ^{[1
,2
]}

Yan, Mengyi ^{[1
,2
]}

Yang, Ni ^{[1
,2
]}

Kong, Renjiang ^{[3
]}

Li, Shiying ^{[1
,2
]}

Ti, Huihui ^{[4
]}

Cheng, Hong ^{[3
]}

机构：

[1] Guangzhou Med Univ, Sch Pharmaceut Sci, Guangdong Prov Key Lab Mol Target & Clin Pharmacol, NMPA & State Key Lab Resp Dis, Guangzhou 511436, Peoples R China

[2] Guangzhou Med Univ, Affiliated Hosp 5, Guangzhou 511436, Peoples R China

[3] Southern Med Univ, Biomat Res Ctr, Sch Biomed Engn, Guangzhou 510515, Peoples R China

[4] Guangdong Pharmaceut Univ, Sch Chinese Med Resource, Guangzhou 510006, Peoples R China

来源：

JOURNAL OF CONTROLLED RELEASE | 2023年 / 358卷

基金：

中国国家自然科学基金;

关键词：

Antiparasitic drug; Tumor hypoxia; Mitochondria dysfunction; Oxidative phosphorylation; Photodynamic therapy; CANCER; IVERMECTIN; NANOPARTICLES; TRANSPORT; PHOTOSENSITIZER; METABOLISM; PROGRESS; TARGETS;

D O I：

10.1016/j.jconrel.2023.05.023

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

As most solid tumors are characterized by a hypoxic microenvironment, enormous efforts have been made to develop strategies to fight hypoxia. This study shows that ivermectin (IVM), an antiparasitic drug, is able to alleviate tumor hypoxia by inhibiting mitochondrial respiration. We explore this to strengthen oxygen-dependent photodynamic therapy (PDT) using chlorin e6 (Ce6) as a photosensitizer. To synergize their pharmacological behaviors, Ce6 and IVM are encapsulated into stable Pluronic F127 micelles. The micelles are uniform in size and seem well-suited for the co-delivery of Ce6 and IVM. The micelles could passively target the drugs into tumors and enhance their cellular internalization. Most importantly, through mitochondrial dysfunction, the micelles reduce the oxygen consumption (making the tumor less hypoxic). Consequently, the production of reactive oxygen species would be increase which, in turn, improves the efficacy of PDT against hypoxic tumors.

引用

页码：654 / 666

页数：13

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