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Amplification of reactive oxygen species (ROS) generation through covalent conjugation of bovine serum albumin (BSA) with newly synthesized, ROS-producing carbon dots (CDs) upon visible light irradiation is reported for the first time. Derivatization of surface carboxyl functional groups of Anthrarufin-derived, green-emitting CD with the amine functionality of BSA ushers distinct changes in the photophysics of CD including an unprecedented ∼50 nm shift in its excitation maxima, decrease in fluorescence lifetime, and concomitant increase in ROS generation. Substantial conformational changes of BSA were witnessed upon conjugation with CD, rendering the BSA-CD conjugate resistant to pepsinolysis. A protease-proof nanoassembly was derived from the BSA-CD conjugate through desolvation that simultaneously hosts a prototype antibiotic and generates ROS with excellent efficiency, making it an attractive platform for antibacterial photodynamic therapy (A-PDT) applications. Systemic annihilation of both Gram-positive and -negative bacteria was achieved with the BSA-CD nanoassembly and envisioned as alternatives to traditional photosensitizers.

BackgroundAmphotericin B (AmB) as a liposomal formulation of AmBisome is the first line of treatment for the disease, visceral leishmaniasis, caused by the parasite Leishmania donovani. However, nephrotoxicity is very common due to poor water solubility and aggregation of AmB. This study aimed to develop a water-soluble covalent conjugate of gold nanoparticle (GNP) with AmB for improved antileishmanial efficacy and reduced cytotoxicity.MethodsCitrate-reduced GNPs (~39 nm) were functionalized with lipoic acid (LA), and the product GNP-LA (GL ~46 nm) was covalently conjugated with AmB using carboxyl-to-amine coupling chemistry to produce GNP-LA-AmB (GL-AmB ~48 nm). The nanoparticles were characterized by dynamic light scattering, transmission electron microscopy (TEM), and spectroscopic (ultraviolet–visible and infrared) methods. Experiments on AmB uptake of macrophages, ergosterol depletion of drug-treated parasites, cytokine ELISA, fluorescence anisotropy, flow cytometry, and gene expression studies established efficacy of GL-AmB over standard AmB.ResultsInfrared spectroscopy confirmed the presence of a covalent amide bond in the conjugate. TEM images showed uniform size with smooth surfaces of GL-AmB nanoparticles. Efficiency of AmB conjugation was ~78%. Incubation in serum for 72 h showed <7% AmB release, indicating high stability of conjugate GL-AmB. GL-AmB with AmB equivalents showed ~5-fold enhanced antileishmanial activity compared with AmB against parasite-infected macrophages ex vivo. Macrophages treated with GL-AmB showed increased immunostimulatory Th1 (IL-12 and interferon-γ) response compared with standard AmB. In parallel, AmB uptake was ~5.5 and ~3.7-fold higher for GL-AmB-treated (P<0.001) macrophages within 1 and 2 h of treatment, respectively. The ergosterol content in GL-AmB-treated parasites was ~2-fold reduced compared with AmB-treated parasites. Moreover, GL-AmB was significantly less cytotoxic and hemolytic than AmB (P<0.01).ConclusionGNP-based delivery of AmB can be a better, cheaper, and safer alternative than available AmB formulations.

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A two-step methodology for simultaneous conjugation of DNA and poly(vinylpyrrolidone) (PVP) polymer to a single carbon quantum dot (CD) is demonstrated for the first time to fabricate a pH-responsive DNA−CD−PVP hybrid hydrogel. Cross-linking in the hydrogel was achieved using CD as the common nucleus through the formation of DNA I-motif conformation at neutral to acidic pH and noncovalent interaction of PVP that infuse self-healing and shape memory properties in the hydrogel. The hydrogel is capable of loading and sustained delivery of drugs for more than 2 weeks as demonstrated using a model drug, Hemin. The quenching of fluorescence of CD by Hemin was trackable even through simple visual monitoring, which showed that Hemin can diffuse from the loaded part to the unloaded part of the hydrogel during the self-healing process. Most significantly, the chosen CD generates reactive oxygen species (ROS) upon visible light irradiation, armoring the hydrogel with worthy antimicrobial activity. Biocompatibility of the DNA−CD−PVP hydrogel was established on human fibroblast cells, indicating their potential use in biomedical area pertaining to wound healing.

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Factual failure in decimating global concerns related to toxic heavy metal ions even after a decent amount of research, calls forth an inexpensive, intelligent sensing platform for fast, accurate, and...