TY - JOUR
T1 - Anti-LDLR modified TPZ@Ce6-PEG complexes for tumor hypoxia-Targeting chemo-/radio-/photodynamic/photothermal therapy
AU - Song, Chuanhui
AU - Xu, Wenguang
AU - Wei, Zheng
AU - Ou, Changjin
AU - Wu, Jinhui
AU - Tong, Jinlong
AU - Cai, Yu
AU - Dong, Xiaochen
AU - Han, Wei
N1 - Publisher Copyright:
This journal is © The Royal Society of Chemistry.
PY - 2020
Y1 - 2020
N2 - Hypoxia, a state of low oxygen tension in solid tumors, is not only closely correlated with resistance to both radiotherapy and chemotherapy, but also associated with poor prognosis of tumors and regional lymph node status. Herein, based on the analysis of cell samples from tumor patients, low-density lipoprotein receptor (LDLR) was found to be overexpressed on the surface of hypoxic tumor cell membranes, and confirmed to be an effective hypoxia marker through specific binding with anti-LDLR antibody in solid tumors. In addition, using the special therapeutic microenvironment of hypoxia, tirapazamine (TPZ, which can be used as both a hypoxia-Activated chemotherapy prodrug and radiotherapy sensitizer) was integrated with PEGylated photosensitizer chlorin e6 (Ce6-PEG) by self-Assembly, and anti-LDLR was then modified on the surface to form tumor hypoxia-Targeting multifunctional nanoparticles (CPTA). CPTA possesses a multimodal antitumor effect via a simultaneous photothermal therapy (PTT)/photodynamic therapy (PDT) effect generated by Ce6, and chemotherapy/radiotherapy actions sensitized by TPZ. It is noteworthy that tumor oxygen was consumed in the process of PDT and the hypoxia was subsequently exacerbated, which can greatly increase the TPZ-sensitized chemotherapy and lead to a synergistic antitumor effect. Both in vitro and in vivo experiments demonstrated that CPTA possesses an excellent therapeutic effect through PTT, PDT, and TPZ sensitized radiotherapy and chemotherapy. This hypoxic tumor targeting synergetic therapeutic strategy has great potential for future clinical transformation.
AB - Hypoxia, a state of low oxygen tension in solid tumors, is not only closely correlated with resistance to both radiotherapy and chemotherapy, but also associated with poor prognosis of tumors and regional lymph node status. Herein, based on the analysis of cell samples from tumor patients, low-density lipoprotein receptor (LDLR) was found to be overexpressed on the surface of hypoxic tumor cell membranes, and confirmed to be an effective hypoxia marker through specific binding with anti-LDLR antibody in solid tumors. In addition, using the special therapeutic microenvironment of hypoxia, tirapazamine (TPZ, which can be used as both a hypoxia-Activated chemotherapy prodrug and radiotherapy sensitizer) was integrated with PEGylated photosensitizer chlorin e6 (Ce6-PEG) by self-Assembly, and anti-LDLR was then modified on the surface to form tumor hypoxia-Targeting multifunctional nanoparticles (CPTA). CPTA possesses a multimodal antitumor effect via a simultaneous photothermal therapy (PTT)/photodynamic therapy (PDT) effect generated by Ce6, and chemotherapy/radiotherapy actions sensitized by TPZ. It is noteworthy that tumor oxygen was consumed in the process of PDT and the hypoxia was subsequently exacerbated, which can greatly increase the TPZ-sensitized chemotherapy and lead to a synergistic antitumor effect. Both in vitro and in vivo experiments demonstrated that CPTA possesses an excellent therapeutic effect through PTT, PDT, and TPZ sensitized radiotherapy and chemotherapy. This hypoxic tumor targeting synergetic therapeutic strategy has great potential for future clinical transformation.
UR - http://www.scopus.com/inward/record.url?scp=85078685249&partnerID=8YFLogxK
U2 - 10.1039/c9tb02248a
DO - 10.1039/c9tb02248a
M3 - 文章
C2 - 31898718
AN - SCOPUS:85078685249
SN - 2050-750X
VL - 8
SP - 648
EP - 654
JO - Journal of Materials Chemistry B
JF - Journal of Materials Chemistry B
IS - 4
ER -