Anticancer prodrugs have been extensively investigated to lower toxic side effects of common chemotherapeutic agents in biomedical fields. To illustrate the activation mechanism of anticancer prodrugs, fluorescent dyes or single-emission intensity alteration-based approaches have been widely used. However, fluorescent dyes often suffer from poor photostability and chemical stability, and single-emission intensity alteration-based methods cannot avoid the influence from uncontrolled microenvironment changes in living samples. To overcome these obstacles, herein, a fluorescence resonance energy transfer (FRET)-based ratiometric approach was successfully developed for real-time monitoring of anticancer prodrug activation. Excitation-wavelength-dependent and full-color-emissive carbon dots (CDs) were used as drug nanocarriers and FRET donor, and a cisplatin(IV) prodrug was selected as the model drug and the linker to load the Dabsyl quencher on the surface of CDs. Owing to the FRET effect, the blue fluorescence of CDs was effectively quenched by the Dabsyl unit. Under reductive conditions in solution or in living cells for the reduction of cisplatin(IV) prodrug to Pt(II) species, the blue fluorescence of CDs increased over time, without apparent intensity change for green or red fluorescence. Thus, the gradually enhanced intensity ratio of blue-to-green or blue-to-red fluorescence could be indicative of the real-time reduction of the cisplatin(IV) prodrug to cytotoxic Pt(II) species. This ratiometric method could exclude the influence from complex biological microenvironments by using green or red fluorescence of CDs as an internal reference, which provides new insights into the activation of the cisplatin(IV) prodrug and offers a great opportunity to design safe and effective anticancer therapeutics.
Chemotherapeutic DNA‐modifying cisplatin and topoisomerase II (TOP2)‐inhibiting doxorubicin (DOX) were co‐administrated by full‐color emissive carbon dots (CDs−Pt(IV)−DOX) through tumor intracellular environment responsive covalent bonds to successfully reverse the resistance of cisplatin in cancer therapy. Cisplatin was loaded in the form of cisplatin(IV) prodrug and DOX was conjugated via a pH‐sensitive hydrazone bond. The internalization process of CDs−Pt(IV)−DOX by cancer cells could be monitored through multicolor emission from CDs and DOX. Upon uptake, cisplatin(IV) prodrug was activated to cytotoxic cisplatin under intracellular reductive condition, and the hydrazone bond was hydrolyzed to release DOX in intracellular weakly acidic environment. The released cisplatin and DOX exhibited combined anticancer effects via different mechanisms of action. Fluorescence imaging, a cytotoxicity study, and an apoptosis assay using CDs−Pt(IV)−DOX were performed to demonstrate the effective uptake and potent therapeutic efficacy toward A2780 and A2780cis cancer cells with cisplatin resistance. The developed CDs−Pt(IV)−DOX offers a promising fluorescent CD‐based co‐administration system for combating cisplatin resistance in cancer treatment.
With the ongoing Flint and Newark water crises, heavy metal ions (HMIs) detection is imperative to safeguard against its detrimental effects. Some conventional methods to detect HMIs include optical emission spectroscopy (OES) and atomic absorption spectroscopy (AAS). However, these techniques are considered to be time-consuming, labour-intensive, costly, and require specialized technical personnel to operate complex instrumentation. Moreover, it is not amenable to on-site HMIs analysis in remote locations due to the centralized nature of these methods. As such, colorimetric sensors have gained traction due to its ease of operation, cost-effectiveness, and are readily deployable as its operation can be decentralized. Herein, we employ ZnS sensor-on-paper for colorimetric detection of HMIs and harness the synergistic concepts of superhydrophobicity and chalcogenide activation to enhance the sensor's analytical response. Characterization of the sensor before and after exposure to HMIs, selectivity studies and practical applications of our sensor-on-paper device would also be discussed. The LOD achieved by the sensor was determined to be 1 μM (for Pb 2+ , Cu 2+ , and Hg 2+ ) and 10 μM (for Ag + ). This challenging journey would not be possible without the support of this team of people God has blessed me with. Firstly, I would like to express my sincere gratitude to my supervisor, Assistant Professor Lee Hiang Kwee, for his unwavering support and insightful guidance in my research journey. Thank you for graciously accepting me as a transfer student, helping me transition seamlessly into the group, encouraging me to challenge the status quo, and guiding me to gain my own footing in the project. Thank you for introducing me to the vibrant and intriguing world of colorimetric chemistry. It has certainly added many colours into my life. The project would not be possible without your immeasurable and upbeat encouragement to keep going after encountering the numerous standstills, defeats, and seemingly dead ends. Under your tutelage, I've grown immensely.I would like to convey my utmost appreciation to my greatest pillar of support: my dear family members for their kind support and understanding. Special thanks to my past and present counsellors, Mr Zeb Lim Kai Kok and Ms Monica Christine Fernando, for always watching out for me and kind concern for my well-being. I'd also like to thank Dr Deblin Jana and Le Hong Tho for kindly teaching me XPS so that I can run XPS independently and confidently.Lastly, I owe a huge debt of gratitude to my biggest cheerleader, intellectual lodestar, and muse outside of school, Tigger, who convinced me that age is not a stumbling block in graduate school and helping me see that having left school for a couple of years to work in the industry would not be as much of a major handicap as I initially thought it to be. Thank you for offering me fresh perspectives to take the leap of faith to get started in the first place, convincing me that there is always light at the end of the tunnel when ev...
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