"Three Musketeers" Enhances Photodynamic Effects by Reducing Tumor Reactive Oxygen Species Resistance

Xu, Wencheng1,2; Qian, Yanrong2; Qiao, Luying2; Li, Lei2; Xie, Yulin2; Sun, Qianqian2; Quan, Zewei3; Li, Chunxia1,2

2024-05-14

10.1021/acsami.4c04278

ACS APPLIED MATERIALS & INTERFACES   影响因子和分区

1944-8244

1944-8252

Photodynamic therapy (PDT) based on upconversion nanoparticles (UCNPs) has been widely used in the treatment of a variety of tumors. Compared with other therapeutic methods, this treatment has the advantages of high efficiency, strong penetration, and controllable treatment range. PDT kills tumors by generating a large amount of reactive oxygen species (ROS), which causes oxidative stress in the tumor. However, this killing effect is significantly inhibited by the tumor's own resistance to ROS. This is because tumors can either deplete ROS by high concentration of glutathione (GSH) or stimulate autophagy to eliminate ROS-generated damage. Furthermore, the tumor can also consume ROS through the lactic acid metabolic pathway, ultimately hindering therapeutic progress. To address this conundrum, we developed a UCNP-based nanocomposite for enhanced PDT by reducing tumor ROS resistance. First, Ce6-doped SiO2 encapsulated UCNPs to ensure the efficient energy transfer between UCNPs and Ce6. Then, the biodegradable tetrasulfide bond-bridged mesoporous organosilicon (MON) was coated on the outer layer to load chloroquine (CQ) and alpha-cyano4-hydroxycinnamic acid (CHCA). Finally, hyaluronic acid was utilized to modify the nanomaterials to realize an active-targeting ability. The obtained final product was abbreviated as UCNPs@MON@CQ/CHCA@HA. Under 980 nm laser irradiation, upconverted red light from UCNPs excited Ce6 to produce a large amount of singlet oxygen (O-1(2)), thus achieving efficient PDT. The loaded CQ and CHCA in MON achieved multichannel enhancement of PDT. Specifically, CQ blocked the autophagy process of tumor cells, and CHCA inhibited the uptake of lactic acid by tumor cells. In addition, the coated MON consumed a high level of intracellular GSH. In this way, these three functions complemented each other, just as the "three musketeers" punctured ROS resistance in tumors from multiple angles, and both in vitro and in vivo experiments had demonstrated the elevated PDT efficacy of nanomaterials.

rare earth upconversion nanoparticles ROS resistance photodynamic therapy autophagyinhibition

SCI ; EI

英语

通讯

National Natural Science Foundation of China["52250077","52272156","52202175"] ; National Natural Science Foundation of China[ts20190911] ; Taishan Scholars Project[2022A1515010461] ; Guangdong Basic and Applied Basic Research Foundation[2021ZDZX2049] ; Guangdong Education Department[ZR2022QE044]

Science & Technology - Other Topics ; Materials Science

Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary

WOS:001225236200001

AMER CHEMICAL SOC

Web of Science

1.Shandong Univ, Shenzhen Res Inst, Shenzhen 518057, Guangdong, Peoples R China
2.Shandong Univ, Inst Frontier Chem, Sch Chem & Chem Engn, Qingdao 266237, Shandong, Peoples R China
3.Southern Univ Sci & Technol SUSTech, Dept Chem, Shenzhen 518055, Guangdong, Peoples R China

Xu, Wencheng,Qian, Yanrong,Qiao, Luying,et al. "Three Musketeers" Enhances Photodynamic Effects by Reducing Tumor Reactive Oxygen Species Resistance[J]. ACS APPLIED MATERIALS & INTERFACES,2024,16(20).

Xu, Wencheng.,Qian, Yanrong.,Qiao, Luying.,Li, Lei.,Xie, Yulin.,...&Li, Chunxia.(2024)."Three Musketeers" Enhances Photodynamic Effects by Reducing Tumor Reactive Oxygen Species Resistance.ACS APPLIED MATERIALS & INTERFACES,16(20).

Xu, Wencheng,et al.""Three Musketeers" Enhances Photodynamic Effects by Reducing Tumor Reactive Oxygen Species Resistance".ACS APPLIED MATERIALS & INTERFACES 16.20(2024).