Protoporphyrin IX-loaded albumin nanoparticles reverse cancer chemoresistance by enhancing intracellular reactive oxygen species

Xiaolin Xu; Chenglong Wang; Wencai Guan; Fanchen Wang; Xin Li; Jia Yuan; Guoxiong Xu

doi:10.1016/j.nano.2023.102688

Protoporphyrin IX-loaded albumin nanoparticles reverse cancer chemoresistance by enhancing intracellular reactive oxygen species

Nanomedicine. 2023 Jul:51:102688. doi: 10.1016/j.nano.2023.102688. Epub 2023 Apr 28.

Authors

Xiaolin Xu¹, Chenglong Wang², Wencai Guan³, Fanchen Wang¹, Xin Li¹, Jia Yuan¹, Guoxiong Xu⁴

Affiliations

¹ Research Center for Clinical Medicine, Jinshan Hospital, Fudan University, Shanghai 201508, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
² Research Center for Clinical Medicine, Jinshan Hospital, Fudan University, Shanghai 201508, China. Electronic address: aaron-wang@alumni.sjtu.edu.cn.
³ Research Center for Clinical Medicine, Jinshan Hospital, Fudan University, Shanghai 201508, China.
⁴ Research Center for Clinical Medicine, Jinshan Hospital, Fudan University, Shanghai 201508, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China. Electronic address: guoxiong.xu@fudan.edu.cn.

PMID: 37121460
DOI: 10.1016/j.nano.2023.102688

Abstract

Chemoresistance is the main cause of chemotherapy failure in ovarian cancer (OC). The enhanced scavenging of reactive oxygen species (ROS) by the thioredoxin system resulted in insufficient intracellular concentrations of effective ROS, leading to chemoresistance. To induce OC cell apoptosis by enhancing intracellular ROS levels, protoporphyrin IX (PpIX) and albumin-bound PTX nanoparticles (APNP) were utilized to fabricate APNP-PpIX nanoparticles. APNP-PpIX effectively generated ROS and increased the effective ROS concentration in chemoresistant cancer cells. The in vitro and in vivo experiments confirmed the effective inhibition of APNP-PpIX on chemoresistant OC cell proliferation and tumor formation. APNP-PpIX significantly improved the effectiveness of chemotherapy and photodynamic therapy, thus providing a new approach for the clinical treatment of chemoresistant OC.

Keywords: Chemoresistance; Nanoparticle; Ovarian cancer; Protoporphyrin; Thioredoxin.

MeSH terms

Cell Line, Tumor
Drug Resistance, Neoplasm
Humans
Nanoparticles*
Neoplasms*
Photochemotherapy* / methods
Photosensitizing Agents / pharmacology
Reactive Oxygen Species

Substances

Photosensitizing Agents
Reactive Oxygen Species
protoporphyrin IX