Anti-HER2 Immunoliposomes: Antitumor Efficacy Attributable to Targeted Delivery of Anthraquinone-Fused Enediyne.
Adv Sci (Weinh)
; 11(17): e2307865, 2024 May.
Article
in En
| MEDLINE
| ID: mdl-38355309
ABSTRACT
Although natural products are essential sources of small-molecule antitumor drugs, some can exert substantial toxicities, limiting their clinical utility. Anthraquinone-fused enediyne natural products are remarkably potent antitumor drug candidates, and uncialamycin and tiancimycin (TNM) A are under development as antibody-drug conjugates. Herein, a novel drug delivery system is introduced for TNM A using anti-human epidermal growth factor receptor 2 (HER2) immunoliposomes (ILs). Trastuzumab-coated TNM A-loaded ILs (HER2-TNM A-ILs) is engineered with an average particle size of 182.8 ± 2.1 nm and a zeta potential of 1.75 ± 0.12 mV. Compared with liposomes lacking trastuzumab, HER2-TNM A-ILs exhibited selective toxicity against HER2-positive KPL-4 and SKBR3 cells. Coumarin-6, a fluorescent TNM A surrogate, is encapsulated within anti-HER2 ILs; the resultant ILs have enhanced cellular uptake in KPL-4 and SKBR3 cells when compared with control liposomes. Furthermore, ILs loaded with more Cy5.5 accumulated in KPL-4 mouse tumors. A single HER2-TNM A-IL dose (0.02 mg kg-1) suppressed the growth of HER2-positive KPL-4 mouse tumors without apparent toxicity. This study not only provides a straightforward method for the effective delivery of TNM A against HER2-positive breast tumors but also underscores the potential of IL-based drug delivery systems when employing highly potent cytotoxins as payloads.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Anthraquinones
/
Drug Delivery Systems
/
Receptor, ErbB-2
/
Enediynes
/
Liposomes
/
Antineoplastic Agents
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Adv Sci (Weinh)
Year:
2024
Type:
Article
Affiliation country:
China