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

Abstract

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 Cu 2+ 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 Cu 2+ ions), and the results are mesmerizing. Moreover, the FL quenching phenomena of HoCDGNPs in the presence of Cu 2+ 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.

Fabrication of a Vitamin B12-Loaded Carbon Dot/Mixed-Ligand Metal Organic Framework Encapsulated within the Gelatin Microsphere for pH Sensing and In Vitro Wound Healing Assessment

“…The maximum FL intensity of FMOF@MS is noted at pH 8; at this pH, deprotonation of the surface carboxylic groups of the CD increases the scope of formation of the delocalized π bonds and “n” electron; as a result, a new surface state with a low band gap is formed, and sharp FL intensity is recorded. , FL emission intensity significantly diminished when the pH decreased from 6 to 4 and in the basic pH medium (pH 9). This drop in FL intensity in the pH range of 6–4 might be the effective energy transfer process induced by the proton saturation of NH 3 + of gelatin which does not allow additional protons in the nitrogen atoms. , At pH 9, the reduced FL intensity could be credited to the improved energy transfer process mediated by the donor–acceptor interaction between the gelatin scaffold and the FMOF. , Besides, in the basic medium, the concentration of OH – ions served as an FL quencher and contributed to FL intensity reduction at this pH . The change in normalized FL intensity with pH variation from 5 to 8 (inset of Figure b) was well fitted in a linear fitting curve ( R 2 = 0.96) and is presented by the following equation normalp normalH = ( F L + 1.21 ) / 0.27 …”

“…Furthermore, observation dictates a single crystalline nature of the CD with a 2.1 Å lattice spacing value, consistent with the inter-planar lattice distance of the graphitic carbon from the (100) plane. 18,19 The microstructure of the FMOF and MOF is also observed by TEM, and a cubic crystal-like structure is found for both samples (Figure S3b,c). The structure of the FMOF is slightly distorted upon incorporating CDs, which is in good agreement with FESEM and PXRD data.…”

“…Although the exact reason behind the emission of CDs and their conjugated system is still not fully clear, in our view, this emission probably comes from the π−π* transition of C�C groups. 19 After the incorporation of the CD into the MOF, intensity fell drastically, and the emission wavelength slightly blue-shifted (438 nm). In contrast, the pristine MOF remained indifferent and did not respond upon excitation at 350 nm (as shown in Figure 3a).…”

“…This drop in FL intensity in the pH range of 6−4 might be the effective energy transfer process induced by the proton saturation of NH 3 + of gelatin which does not allow additional protons in the nitrogen atoms. 19,33 At pH 9, the reduced FL intensity could be credited to the improved energy transfer process mediated by the donor−acceptor interaction between the gelatin scaffold and the FMOF. 18,35 Besides, in the basic medium, the concentration of OH − ions served as an FL quencher and contributed to FL intensity reduction at this pH.…”

“…12,13,16,17 Moreover, our previous work also explored the pH sensitivity of CDs. 18,19 The deprotonation and protonation of the surface functional groups depending upon the medium pH are mainly responsible for the pH-dependent fluorescence (FL) emission. This pH sensing ability is exploited here for monitoring wound pH alteration.…”