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Tumor Microenvironment Triggered the In Situ Synthesis of an Excellent Sonosensitizer in Tumor for Sonodynamic
Wei-Qiang Huang1,2, Ya-Qi Zhu3, Wei You2
1The Department of Pharmacy, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230026, China.
Abstract:
An ultrasound-triggered sonodynamic therapy has shown great promise for cancer therapy. However, its clinical applications are very limited because the traditional sonosensitizers tend to suffer from very poor efficiency combined with low retention in cancer cells and low tumor selectivity. Therefore, sonosensitizers with higher effectivity, higher tumor cell retention, and higher tumor cell specificity are highly required. Herein, we constructed a Ti2C(OH)X nanosheet, which was a poor sonosensitizer but had a long circulation in the blood system. However, it was very interesting to find that the tumor microenvironment could in situ turn Ti2C(OH)X nanosheet into a novel and excellent sonosensitizer with a nanofiber structure in tumors, exhibiting excellent ability to generate reactive oxygen species (ROS) under ultrasound. Moreover, the nanofiber structure made it very difficult to get out of cancer cells, highly enhancing the retention of the sonosensitizer in the tumor, thereby enabling it to effectively and selectively kill cancer cells in vivo. Our findings demonstrate that the strategy of the tumor microenvironment triggering the in situ synthesis of an effective sonosensitizer in tumor provided a promising means to simultaneously increase the efficiency, sonosensitizer retention in cancer cells, and cancer selectivity, thereby effectively killing cancer cells but causing little damage to healthy tissues via the sonodynamic therapy.
Insights
This study introduces a novel approach for cancer therapy using ultrasound-triggered sonodynamic therapy. A Ti2C(OH) nanosheet transforms in the tumor microenvironment into an effective sonosensitizer, enhancing cancer cell retention and selectivity for improved treatment outcomes.
Area of Science:
- Biomedical Engineering
- Materials Science
- Oncology
Background:
- Ultrasound-triggered sonodynamic therapy (SDT) shows promise for cancer treatment.
- Current SDT faces limitations due to poor sonosensitizer efficiency, low cancer cell retention, and lack of tumor selectivity.
- Development of highly effective, tumor-specific sonosensitizers with enhanced retention is crucial for clinical translation.
Purpose of the Study:
- To engineer a novel sonosensitizer system for enhanced cancer therapy.
- To leverage the tumor microenvironment for *in situ* activation and structural transformation of a sonosensitizer.
- To improve sonosensitizer efficiency, cancer cell retention, and tumor selectivity in sonodynamic therapy.
Main Methods:
- Construction of a Ti2C(OH) nanosheet with poor initial sonosensitizing properties but long blood circulation.
- Exploitation of the tumor microenvironment to induce *in situ* transformation of the nanosheet into a nanofiber-structured sonosensitizer.
- Evaluation of reactive oxygen species (ROS) generation under ultrasound, cancer cell retention, and *in vivo* anti-cancer efficacy.
Main Results:
- The Ti2C(OH) nanosheet was successfully transformed *in situ* within the tumor microenvironment into an efficient nanofiber-structured sonosensitizer.
- The transformed sonosensitizer exhibited enhanced reactive oxygen species (ROS) generation under ultrasound.
- The nanofiber structure significantly improved retention within cancer cells, leading to effective and selective tumor cell killing *in vivo*.
Conclusions:
- The tumor microenvironment can be utilized to trigger the *in situ* synthesis of potent sonosensitizers.
- This strategy simultaneously enhances SDT efficiency, sonosensitizer retention in cancer cells, and tumor selectivity.
- The developed approach offers a promising method for effective cancer cell killing with minimal damage to healthy tissues.
