Manganese-induced Photothermal-Ferroptosis for Synergistic Tumor Therapy

Chen, Kun1,2,3; Sun, Rui1,2,3,4; Guan, Yudong5; Fang, Tao1,2,3; Tao, Jun6; Li, Zhijie5; Zhang, Bingchen4; Yu, Zhiqiang4; Tian, Jiahang1,2,3; Teng, Zhaogang6; Wang, Jigang1,2,3,5,7,8,9

2024-08-01

10.1016/j.jconrel.2024.06.053

JOURNAL OF CONTROLLED RELEASE   影响因子和分区

0168-3659

1873-4995

Ferroptosis-related tumor therapy based on nanomedicines has recently gained significant attention. However, the therapeutic performance is still hindered by the tumor 's physical barriers such as the fibrotic tumor matrix and elevated interstitial fluid pressure, as well as chemical barriers like glutathione (GSH) overabundance. These physicochemical barriers impede the bioavailability of nanomedicines and compromise the therapeutic efficacy of lipid reactive oxygen species (ROS). Thus, this study pioneers a manganese-mediated overcoming of physicochemical barriers in the tumor microenvironment using organosilica-based nanomedicine (MMONs), which bolsters the synergy of photothermal-ferroptosis treatment. The MMONs display commendable proficiency in overcoming tumor physical barriers, due to their MnO 2 -mediated shape-morphing and softness-transformation ability, which facilitates augmented cellular internalization, enhanced tumor accumulation, and superior drug penetration. Also, the MMONs possess excellent capability in chemical barrier overcoming, including MnO 2 - mediated dual GSH clearance and enhanced ROS generation, which facilitates ferroptosis and heat shock protein inhibition. Notably, the resulting integration of physical and chemical barrier overcoming leads to amplified photothermal-ferroptosis synergistic tumor therapy both in vitro and in vivo . Accordingly, the comparative proteomic analysis has identified promoted ferroptosis with a transient inhibitory response observed in the mitochondria. This research aims to improve treatment strategies to better fight the complex defenses of tumors.

Organosilica Photothermal therapy Physicochemical barriers Manganese dioxide

SCI ; EI

英语

通讯

National Key Research and Development Program of China[2022YFC2303600] ; Scientific and technological innovation project of China Academy of Chinese Medical Sciences["CI2023D003","CI2021B014"] ; CACMS Innovation Fund["CI2023E002","CI2021A05101","CI2021A05104"] ; Science and Technology Foundation of Shenzhen[JCYJ20210324115800001] ; Shenzhen Medical Research Fund[B2302051] ; National Natural Science Foundation of China["81971675","22275099","32101189"] ; Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine[ZYYCXTD-C-202002] ; Shenzhen Medical Research Fund of Shenzhen Medical Academy of Research and Translation[B2302051] ; Distinguished Expert Project of Sichuan Province Tianfu Scholar[CW202002] ; Fundamental Research Funds for the Central Public Welfare Research Institutes[ZZ13-ZD-07] ; Shenzhen Science and Technology Program[RCBS20210609104421046]

Chemistry ; Pharmacology & Pharmacy

Chemistry, Multidisciplinary ; Pharmacology & Pharmacy

WOS:001260774700001

ELSEVIER

PHARMACOLOGY & TOXICOLOGY

Web of Science

1.Southern Med Univ, Sch Pharmaceut Sci, NMPA Key Lab Res & Evaluat Drug Metab, Guangzhou 510515, Peoples R China
2.Southern Med Univ, Sch Pharmaceut Sci, Guangdong Prov Key Lab New Drug Screening, Guangzhou 510515, Peoples R China
3.Southern Med Univ, Sch Pharmaceut Sci, Guangdong Hongkong Macao Joint Lab New Drug Screen, Guangzhou 510515, Guangdong, Peoples R China
4.Southern Med Univ, Dongguan Peoples Hosp, Dongguan Inst Clin Canc Res, Dept Lab Med,Affiliated Hosp 10, Dongguan 523018, Peoples R China
5.Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Affiliated Hosp 1, Dept Urol, Shenzhen 518020, Guangdong, Peoples R China
6.Nanjing Univ Posts & Telecommun, Inst Adv Mat, Jiangsu Natl Synerget Innovat Ctr Adv Mat, Key Lab Organ Elect & Informat Displays,Jiangsu Ke, Nanjing 210023, Peoples R China
7.China Acad Chinese Med Sci, Artemisinin Res Ctr, State Key Lab Qual Ensurance & Sustainable Use Dao, Beijing 100700, Peoples R China
8.China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing 100700, Peoples R China
9.Henan Univ, Sch Pharm, State Key Lab Antiviral Drugs, Kaifeng 475004, Peoples R China

Chen, Kun,Sun, Rui,Guan, Yudong,et al. Manganese-induced Photothermal-Ferroptosis for Synergistic Tumor Therapy[J]. JOURNAL OF CONTROLLED RELEASE,2024,372.

Chen, Kun.,Sun, Rui.,Guan, Yudong.,Fang, Tao.,Tao, Jun.,...&Wang, Jigang.(2024).Manganese-induced Photothermal-Ferroptosis for Synergistic Tumor Therapy.JOURNAL OF CONTROLLED RELEASE,372.

Chen, Kun,et al."Manganese-induced Photothermal-Ferroptosis for Synergistic Tumor Therapy".JOURNAL OF CONTROLLED RELEASE 372(2024).