Robust and low cytotoxic betaine-based colorimetric pH sensors suitable for cancer cell discrimination

- Zwitterionic betaines being as reversibly and sensitively colorimetric pH sensors.
- The betaines show sharp absorbance and color changes in physiological pH range.
- The colorimetric responses work efficiently in prostate cancer cell extract.
- The betaines feature excellent water solubility and low cytotoxicity.
- A new concept to discriminate cancer cells for diagnostics and targeted therapeutics.

The local pH level in tumor microenvironment usually turns to an acidic range of 5.5-7.0 from the healthy level of 7.4. For this pH change, robust sensors with high sensitivity, water solubility and biocompatibility are highly desirable. Herein, novel zwitterionic betaines were designed and synthesized for the first time as sensitively colorimetric pH sensors which featured low cytotoxicity, excellent water solubility and reversibility. When the solution pH was changed from 5.0 to 7.2, new absorption bands appeared with gradually increased absorbance and were accompanied by naked-eye-visible color changes from yellow to green, indicating a new approach to detect pH changes by a simple ratiometric method. Moreover, these zwitterionic betaine sensors showed promising applications for biological and pathological samples due to their low cytotoxicity. In the pathological samples of prostate cancer cell extract solutions, they displayed sensitively colorimetric responses and strong anti-interference ability to pH changes. Therefore, it is promising for them to be as colorimetric indicators to pH changes in pathological samples for diagnostic and targeted therapeutic purposes.

Novel zwitterionic betaines have been designed and synthesized as colorimetric pH sensors, which feature excellent water solubility, low cytotoxicity, reversibility, sensitivity and suitable for the cancer cell discrimination in the tumor microenvironment.111