Electrical and fluorescence in situ monitoring of tumor microenvironment-based pH-responsive polymer dot coated...

A boronate-ester structure forming a pH-responsive polymer dot (Plu-PD) coated biosensor between carbonized-sp² rich dopamine-alginate [PD(Alg)] and boronic acid-grafted Pluronic (BA-Pluronic) was developed for the electrochemical and fluorescence detection of cancer cells. The reduced fluorescence (FL) resulting from fluorescence resonance energy transfer (FRET) mediated by π-π interactions within Plu-PD was successfully reinvigorated through the specific cleavage of the boronate-ester bond, triggered by the acidic conditions prevailing in the cancer microenvironment. The anomalous variations in extracellular pH levels observed in cancer (pH ∼6.8), as opposed to the normal cellular pH range of approximately 7.4, serve as robust indicators for discerning cancer cells from their healthy counterparts. Moreover, the Plu-PD coated surface demonstrated remarkable adaptability in modulating its surface structure, concurrently exhibiting tunable electroconductivity under reduced pH conditions, thereby imparting selective responsiveness to cancer cells. The pH-modulated conductivity change was validated by a reduction in resistance from 211 ± 9.7 kΩ at pH 7.4 to 73.9 ± 9.4 kΩ and 61.5 ± 11.5 kΩ at pH 6.8 and 6.0, respectively. The controllable electrochemical characteristics were corroborated through in vitro treatment of cancer cells (HeLa, B16F10, and SNU-C2A) via LED experiments and wireless output analysis. In contrast, identical treatments yielded a limited response in normal cell line (CHO-K1). Notably, the Plu-PD coated surface can be seamlessly integrated with a wireless system to facilitate real-time monitoring of the sensing performance in the presence of cancer and normal cells, enabling rapid and accurate cancer diagnosis using a smartphone.