Aptamer functionalized hypoxia-potentiating agent and hypoxia-inducible factor inhibitor combined with hypoxia-activated prodrug for enhanced tumor therapy.
Cancer Lett
; 598: 217102, 2024 Aug 28.
Article
in En
| MEDLINE
| ID: mdl-38969157
ABSTRACT
Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer. Hypoxia-activated prodrugs (HAPs) have shown promise as potential therapeutic agents for TNBC. While increasing hypoxia levels may promote the HAP activation, it raises concerns regarding HIF1α-dependent drug resistance. It is desirable to develop a targeted approach that enhances tumor hypoxia for HAP activation without promoting HIF1α-dependent drug resistance in TNBC treatment. Herein, we proposed a multi-responsive carrier-free self-assembled nanomedicine named AQ4N@CA4T1ASO. This nanomedicine first targeted tumors by the TNBC-targeting aptamers (T1), and then disassembled in the reductive and acidic conditions within tumors. The released Combretastatin 4 (CA4) could exacerbate hypoxia, thereby promoting the conversion of inactive Banoxantrone (AQ4N) to its active form, AQ4. Simultaneously, the released antisense oligonucleotide (ASO) could attenuate hypoxia-induced HIF1α mRNA expression, thereby sensitizing the tumor to chemotherapy. Overall, this smart nanomedicine represents a profound targeted therapy strategy, combining "hypoxia-potentiating, hypoxia-activated, chemo-sensitization" approaches for TNBC treatment. In vivo study demonstrated significant suppression of tumor growth, highlighting the promising potential of this nanomedicine for future clinical translation.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Prodrugs
/
Hypoxia-Inducible Factor 1, alpha Subunit
/
Aptamers, Nucleotide
/
Triple Negative Breast Neoplasms
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Cancer Lett
Year:
2024
Type:
Article
Affiliation country:
China