Lipo/TK-CDN/TPP/Y6 nanoparticles inhibit cutaneous melanoma formation.
J Drug Target
; 32(8): 931-940, 2024 Sep.
Article
in En
| MEDLINE
| ID: mdl-38838039
ABSTRACT
Stimulation of the innate immune stimulator of interferon genes (STING) pathway has been shown to boost anti-tumour immunity. Nevertheless, the systemic delivery of STING agonists to the tumour presents challenges. Therefore, we designed a cyclic dinucleotide (CDN)-based drug delivery system (DDS) combined photothermal therapy (PTT)/photodynamic therapy (PDT)/immunotherapy for cutaneous melanoma. We coencapsulated a reactive oxygen species (ROS)-responsive prodrug thioketone-linked CDN (TK-CDN), and photoresponsive agents chlorin E6 (Y6) within mitochondria-targeting reagent triphenylphosphonium (TPP)-modified liposomes (Lipo/TK-CDN/TPP/Y6). Lipo/TK-CDN/TPP/Y6 exhibited a photothermal effect similar to Y6, along with a superior cellular uptake rate. Upon endocytosis by B16F10 cells, Lipo/TK-CDN/TPP/Y6 generated large amounts of ROS under laser irradiation for PDT. Mice bearing B16F10 tumours were intravenously injected with Lipo/TK-CDN/TPP/Y6 and exposed to irradiation, resulting in a substantial inhibition of tumour growth. Exploration of the mechanism of anti-tumour action showed that Lipo/TK-CDN/TPP/Y6 had a stronger stimulation of STING activation and anti-tumour immune cell infiltration compared to other groups. Hence, the Lipo/TK-CDN/TPP/Y6 nanoparticles offer great potential as a DDS for targeted and on-demand drug release at tumour sites. These nanoparticles exhibit promise as a candidate for precise and controllable combination therapy in the treatment of tumours.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Photochemotherapy
/
Porphyrins
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Skin Neoplasms
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Melanoma, Experimental
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Prodrugs
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Chlorophyllides
/
Reactive Oxygen Species
/
Nanoparticles
/
Liposomes
Limits:
Animals
/
Humans
Language:
En
Journal:
J Drug Target
Journal subject:
FARMACOLOGIA
Year:
2024
Document type:
Article
Affiliation country:
China