%0 Journal Article
%T Aptamer Functionalized Hypoxia-potentiating Agent and Hypoxia-inducible Factor Inhibitor Combined with Hypoxia-activated Prodrug for Enhanced Tumor Therapy.
%A Ma Y
%A Zhang H
%A Shen X
%A Yang X
%A Deng Y
%A Tian Y
%A Chen Z
%A Pan Y
%A Luo H
%A Zhong C
%A Yu S
%A Lu A
%A Zhang B
%A Tang T
%A Zhang G
%J Cancer Lett
%V 0
%N 0
%D 2024 Jul 3
%M 38969157
%F 9.756
%R 10.1016/j.canlet.2024.217102
%X 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.