Targeted Delivery of Circular Single-Stranded DNA Encoding IL-12 for the Treatment of Triple-Negative Breast Cancer.
Adv Healthc Mater
; : e2401376, 2024 Sep 03.
Article
in En
| MEDLINE
| ID: mdl-39226527
ABSTRACT
Interleukin-12 (IL-12) is a critical cytokine with notable anticancer properties, including enhancing T-cell-mediated cancer cell killing, and curbing tumor angiogenesis. To date, many approaches are evaluated to achieve in situ overexpression of IL-12, minimizing leakage and the ensuing toxicity. Here, it is focused on circular single-stranded DNA (Css DNA), a type of DNA characterized by its unique structure, which could be expressed in mammals. It is discovered that Css DNA can induce sustained luciferase expression for half a year by intramuscular injection and showed effective antitumor results by intratumoral injection. Motivated by these findings, a folate-modified LNP system is now developed for the delivery of Css DNA expressing IL-12 for the therapy of 4T1 triple-negative breast cancer (TNBC). This delivery system effectively activates anti-cancer immune responses, slows tumor growth, significantly prolongs survival in animal models, and prevents tumor recurrence. After 6 months of long-term observation, the elevated level of IL-12 is still detectable in the lymph nodes and serum of the cured mice. This study highlights the long-term sustained expression capacity of Css DNA and its ability to inhibit recurrence, and the potential of tumor-targeted LNPs for Css DNA-based cancer therapy, providing a new insight into gene overexpression strategy.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Adv Healthc Mater
/
Adv. healthc. mater
/
Advanced healthcare materials (Print)
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
Germany