Advances in Applications of Polysaccharides and Polysaccharide-Based Materials

Polysaccharides, complex carbohydrates composed of long chains of residues of sugar molecules, have garnered significant attention in recent years due to their diverse applications across various industries [...

A two-photon fluorescent probe records the intracellular pH through 'OR' logic operation via internal calibration

status: publishe

Polysaccharides as Stabilizers for Polymeric Microcarriers Fabrication.

Biodegradable polymeric microparticles are widely used in drug delivery systems with prolonged-release profiles and/or cell microcarriers. Their fabrication via the oil/water emulsion solvent evaporation technique has normally required emulsifiers in the aqueous phase. The present work aims to evaluate the effectiveness of various polysaccharides, such as chitosan, hyaluronic acid, cellulose, arabinogalactan, guar and their derivatives, as an alternative to synthetic surfactants for polylactide microparticle stabilization during their fabrication. Targeted modification of the biopolymer's chemical structure was also tested as a tool to enhance polysaccharides' emulsifying ability. The transformation of biomacromolecules into a form of nanoparticle via bottom-up or top-down methods and their subsequent application for microparticle fabrication via the Pickering emulsion solvent evaporation technique was useful as a one-step approach towards the preparation of core/shell microparticles. The effect of polysaccharides' chemical structure and the form of their application on the polylactide microparticles' total yield, size distribution and morphology was evaluated. The application of polysaccharides has great potential in terms of the development of green chemistry and the biocompatibility of the formed microparticles, which is especially important in biomedicine application

New Insight into a Cancer Theranostic Probe: Efficient Cell-Specific Delivery of SN-38 Guided by Biotinylated Poly(vinyl alcohol)

An optically modulated “turn-on” theranostic prodrug <b>TP1</b> has been explored and formulated with biotinylated poly­(vinyl alcohol) (<b>biotinPVA</b>) to obtain desired pharmacokinetics. <b>TP1</b>, consisting of the antineoplastic camptothecin analogue SN-38, and the fluorescent dye rhodol green have been covalently conjugated through a disulfide bond. Glutathione triggering the release of drug and fluorophore has been well established by UV–vis measurements through mass spectral analysis in physiological conditions. The biocompatible <b>biotinPVA</b> formulated prodrug (<b>PTP1</b>) showed remarkably higher stability against blood serum and cell-specific activation in contrast to that of <b>TP1</b>. Significantly, <b>PTP1</b> permits monitoring of the delivery and release of well-known topoisomerase I inhibitor SN-38 by modulating fluorescence signal at λ_em 550 nm within intracellular milieus. Moreover, theranostic probe <b>PTP1</b> exhibited dose-dependent antiproliferative activity against receptor-positive HeLa cells, whereas it did not show such an effect against receptor-negative NIH3T3 cells. Finally, the cell-specific antiproliferative activity of <b>PTP1</b> via the apoptotic pathway is an efficient approach in cancer theranostics. Thus, futuristic <b>PTP1</b> could be a promising agent in which diagnostic and prognostic data will be monitored synergistically

Cu²⁺-Responsive Bimodal (Optical/MRI) Contrast Agent for Cellular Imaging

A water-soluble T₁ magnetic resonance imaging contrast agent (<b>1</b>) has been synthesized. The bimodal contrast agent <b>1</b> responds to the Cu²⁺ ion in living cells by enhancing the MRI modality signal whereas the optical signal gradually drops. This dual modality probe response depends on the cellular free copper ions in RAW 264.7 cells even at the micromolar level

Direct Fluorescence Monitoring of the Delivery and Cellular Uptake of a Cancer-Targeted RGD Peptide-Appended Naphthalimide Theragnostic Prodrug

Presented here is a multicomponent synthetic strategy that allows for the direct, fluorescence-based monitoring of the targeted cellular uptake and release of a conjugated therapeutic agent. Specifically, we report here the design, synthesis, spectroscopic characterization, and preliminary in vitro biological evaluation of a RGD peptide-appended naphthalimide pro-CPT (compound <b>1</b>). Compound <b>1</b> is a multifunctional molecule composed of a disulfide bond as a cleavable linker, a naphthalimide moiety as a fluorescent reporter, an RGD cyclic peptide as a cancer-targeting unit, and camptothecin (CPT) as a model active agent. Upon reaction with free thiols in aqueous media at pH 7.4, disulfide cleavage occurs. This leads to release of the free CPT active agent, as well as the production of a red-shifted fluorescence emission (λ_max = 535 nm). Confocal microscopic experiments reveal that <b>1</b> is preferentially taken up by U87 cells over C6 cells. On the basis of competition experiments involving okadaic acid, an inhibitor of endocytosis, it is concluded that uptake takes place via RGD-dependent endocytosis mechanisms. In U87 cells, the active CPT payload is released within the endoplasmic reticulum, as inferred from fluorescence-based colocalization studies using a known endoplasmic reticulum-selective dye. The present drug delivery system (DDS) could represent a new approach to so-called theragnostic agent development, wherein both a therapeutic effect and drug uptake-related imaging information are produced and can be readily monitored at the subcellular level. In due course, the strategy embodied in conjugate <b>1</b> could allow for more precise monitoring of dosage levels, as well as an improved understanding of cellular uptake and release mechanisms