Ho3+-Doped Carbon Dot/Gelatin Nanoparticles for pH-Responsive Anticancer Drug Delivery and Intracellular Cu2+ Ion Sensing

Accurate diagnosis with secure and target-specific drug delivery improves the success rate in cancer treatment and patient survival outcomes. The development of stimuli-responsive theranostic with the molecular computing ability could address all these criteria at a time. This work attempts to design a multifunctional biocomputing agent that can serve as a secure and target-specific drug carrier and simultaneously act as a molecular logic device. Hence, we developed holmium-doped carbon dot-gelatin nanoparticles (HoCDGNPs) by two-step desolvation methods and used them as fluorescence (FL) imaging and MRI contrast agents with effective pH and Cu2+ ion sensing ability. Furthermore, Boolean algebraic operations (NOR, OR, IMP, and NIMP) are executed on the HoCDGNP system using the FL/magnetic resonance (MR) response in the presence of different inputs (H+, OH-, and Cu2+ ions), and the results are mesmerizing. Moreover, the FL quenching phenomena of HoCDGNPs in the presence of Cu2+ ions by cupricamine or cupric-carboxylate coordination formation are also exploited in the living HeLa cells. Finally, the resulting system is used for pH-responsive drug delivery of a model anticancer drug (5-fluorouracil), and the release profile is found selective and sustained over the pH range 6-7.4. Thus, it counters the shortcomings associated with the 5-fluorouracil drug administration (short lifetime and poor specificity at high doses). The cellular uptake and cell viability assessment are also accomplished in cancerous and noncancerous cell lines to ensure the acceptability of this multifunctional biocomputing system, and the results are pretty satisfactory.

Automated summary

This study presents the design of a multifunctional biocomputing agent that acts as a secure and target-specific drug carrier while also serving as a molecular logic device. By utilizing fluorescence/magnetic resonance response for Boolean algebraic operations and pH-responsive drug delivery, this system overcomes the limitations of traditional drug administration.