Dual-responsive supramolecular photodynamic nanomedicine with activatable immunomodulation for enhanced antitumor therapy.
10.1016/j.apsb.2023.10.006
- Author:
Siqin HE
1
;
Lulu WANG
1
;
Dongxu WU
2
;
Fan TONG
2
;
Huan ZHAO
3
;
Hanmei LI
4
;
Tao GONG
2
;
Huile GAO
2
;
Yang ZHOU
1
Author Information
1. Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570200, China.
2. Key Laboratory of Drug-Targeting and Drug Delivery System, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
3. Revvity Inc., Waltham, MA 02451, USA.
4. School of Food and Biological Engineering, Chengdu University, Chengdu 610106, China.
- Publication Type:Journal Article
- Keywords:
Checkpoint blockade;
Dual-responsive;
Immunomodulator;
Immunosuppressive microenvironment;
Photodynamic therapy;
Supramolecular assembly
- From:
Acta Pharmaceutica Sinica B
2024;14(2):765-780
- CountryChina
- Language:English
-
Abstract:
A major challenge facing photodynamic therapy (PDT) is that the activity of the immune-induced infiltrating CD8+ T cells is subject to the regulatory T lymphocytes (Tregs), leaving the tumor at risk of recurrence and metastasis after the initial ablation. To augment the antitumor response and reprogram the immunosuppressive tumor microenvironment (TME), a supramolecular photodynamic nanoparticle (DACss) is constructed by the host-guest interaction between demethylcantharidin-conjugated β-cyclodextrin (DMC-CD) and amantadine-terminated disulfide-conjugated FFVLGGGC peptide with chlorin e6 decoration (Ad-ss-pep-Ce6) to achieve intelligent delivery of photosensitizer and immunomodulator for breast cancer treatment. The acid-labile β-carboxamide bond of DMC-CD is hydrolyzed in response to the acidic TME, resulting in the localized release of DMC and subsequent inhibition of Tregs. The guest molecule Ad-ss-pep-Ce6 can be cleaved by a high level of intracellular GSH, reducing photosensitizer toxicity and increasing photosensitizer retention in the tumor. With a significant increase in the CTL/Treg ratio, the combination of Ce6-based PDT and DMC-mediated immunomodulation adequately achieved spatiotemporal regulation and remodeling of the TME, as well as improved primary tumor and in situ lung metastasis suppression with the aid of PD-1 antibody.
