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Direct Readout Hypoxia Tumor Suppression In Vivo through NIR-Theranostic Activation
Yu-Qiang Zhao1, Shayeri Biswas2, Qiuling Chen1
1College of Chemical Science and Technology, Yunnan University, Kunming 650091, P. R. China.
Abstract:
Urgency in finding a suitable therapy in tumor hypoxia strives to develop hypoxia-targeted activatable theranostic. A strategic theranostic prodrug (Azo-M) has been synthesized. Its azo-linker scission under the hypoxia condition has released an near-infrared (NIR)-reporter to determine the extent of chemotherapeutic (melphalan analogue) activation. Under an artificial hypoxia condition, a large shift from 520 to 590 nm in UV absorption was observed in Azo-M. Alongside, the emission maxima had appeared at 625 nm under the said condition. The Azo-M post-incubated HeLa cells have shown upregulation of various apoptotic factors under oxygen deprivation (3%) condition. Azo-M has shown antiproliferative activity under hypoxia conditions in various cancer cells. An ex-vivo biodistribution study indicated that theranostic Azo-M only activated in tumor tissue and to some extent in the liver. The therapeutic activity study in vivo indicated that Azo-M effectively reduced the tumor size and volume (about 2-fold) without the change of bodyweight of mice. The theranostic Azo-M can be a cornerstone to suppress tumor hypoxia and tracking its extent of suppression.
Insights
A novel hypoxia-activated theranostic prodrug, Azo-M, releases a near-infrared reporter and a chemotherapy agent specifically in tumor environments. This targeted approach effectively suppresses tumor hypoxia and reduces tumor size in vivo.
Area of Science:
- Biomedical Engineering
- Cancer Therapy
- Molecular Imaging
Background:
- Tumor hypoxia poses a significant challenge in cancer therapy, necessitating the development of targeted therapeutic strategies.
- Hypoxia-activated theranostics offer a promising approach to simultaneously diagnose and treat tumors under low-oxygen conditions.
Purpose of the Study:
- To synthesize and characterize a novel hypoxia-activatable theranostic prodrug, Azo-M, for targeted cancer therapy.
- To evaluate the drug release, imaging capabilities, and therapeutic efficacy of Azo-M under hypoxic conditions.
Main Methods:
- Synthesis and characterization of the Azo-M theranostic prodrug.
- In vitro studies using HeLa cells to assess drug activation, apoptosis induction, and antiproliferative activity under hypoxia.
- Ex vivo biodistribution and in vivo therapeutic efficacy studies in a mouse model.
Main Results:
- Azo-M demonstrated a distinct spectral shift (520 to 590 nm UV absorption, 625 nm emission) under hypoxia, indicating successful activation.
- Azo-M induced apoptosis in HeLa cells and exhibited antiproliferative effects in various cancer cells under hypoxic conditions.
- In vivo studies showed selective activation in tumor tissue, significant tumor size reduction (2-fold), and no adverse effects on body weight.
Conclusions:
- Azo-M functions as an effective hypoxia-targeted theranostic prodrug, enabling the visualization and suppression of tumor hypoxia.
- The selective activation and therapeutic efficacy of Azo-M suggest its potential as a cornerstone therapy for hypoxic tumors.
