Self-illuminating liposome-derived in situ triggerable photodynamic therapy combining radionuclide therapy for synergistic treatment of lung cancer.
10.1016/j.apsb.2025.06.026
- Author:
Chunsen YUAN
1
;
Taotao JIN
2
;
Hangke LEI
1
;
Juanjuan LIU
2
;
Wendan PU
2
;
Yang ZHANG
2
;
Chenwen LI
2
;
Dingde HUANG
1
;
Jianxiang ZHANG
2
;
Jiawei GUO
3
Author Information
1. Department of Nuclear Medicine, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China.
2. Department of Pharmaceutics, College of Pharmacy, Third Military Medical University (Army Medical University), Chongqing 400038, China.
3. Department of Pharmaceutical Analysis, College of Pharmacy, Third Military Medical University (Army Medical University), Chongqing 400038, China.
- Publication Type:Journal Article
- Keywords:
Antitumor;
Liposome;
Lung cancer;
Photodynamic therapy;
Radiopharmaceutical;
Reactive oxygen species
- From:
Acta Pharmaceutica Sinica B
2025;15(10):4973-4994
- CountryChina
- Language:English
-
Abstract:
The persistent high prevalence and poor survival outcomes of lung cancer underscore the urgent need for innovative therapeutic modalities. Here, we present a novel multifunctional delivery platform for the synergistic treatment of lung malignancies, combining in situ-triggerable photodynamic therapy (PDT) with radiotherapy. The new platform CLL was developed by loading a new reactive oxygen species (ROS)-triggerable photosensitizer, luminol-conjugated chlorin e6 (Ce6), into liposomes. CLL can be activated through the bioluminescence resonance energy transfer effect under oxidative stress, thereby producing singlet oxygen for targeted tumor treatment without external irradiation. In vitro studies showed significant cytotoxic effects of CLL in both 4T1 and A549 tumor cells. Furthermore, a PDT-radiopharmaceutical combination nanotherapy CLL-177Lu was engineered by incorporating the radionuclide 177Lu into CLL. CLL-177Lu demonstrated synergistic antitumor effects in 4T1 and A549 tumor cells, as well as in mouse models of 4T1 breast cancer lung metastasis or A549 tumor xenografts. Mechanistically, CLL-177Lu can induce singlet oxygen/ROS generation, enhance tumor cell apoptosis, and promote M1 macrophage-mediated immunotherapy. Preliminary assessments showed a favorable profile for CLL-177Lu, highlighting its potential as a promising nanotherapy for cancer treatment. Additionally, CLL can serve as a versatile platform for delivering a range of therapies to achieve synergistic antitumor effects.
