Emerging natural polymer-based architectured nanotherapeutics for the treatment of cancer

Kuna, Krishna; Baddam, Sudhakar Reddy; Kalagara, Sudhakar; Akkiraju, Pavan C.; Tade, Rahul S.; Enaganti, Sreenivas

doi:10.1016/j.ijbiomac.2024.129434

Cited by 5 publications

(1 citation statement)

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“…Solid tumors are characterized by a heterogeneous population of neoplastic cells supplied by an irregular and discontinuous endothelium with large gaps between the endothelial cells and abnormally thick or thin-basement membranes, 28 and often they are easily targeted with nanoparticles (NPs)-based drug-delivery systems. 29 Indeed, immunoliposomes or liposomes decorated with monoclonal antibodies or variable monovalent fragments (Fab) promote active targeting 30 or covalently linked to an inhibitor of the extracellular matrix (ECM)-related enzyme, lysyl oxidase 1 (LOX), that inhibits the cross-linking of elastin and collagen fibers. This system once loaded with epirubicin chemotherapeutic exhibited greater inhibition of triple negative breast cancer (TNBC) cell growth.…”

Section: Introductionmentioning

confidence: 99%

PEGylated SOCS3 Mimetics Encapsulated into PLGA-NPs as Selective Inhibitors of JAK/STAT Pathway in TNBC Cells

La Manna,

Cugudda,

Mercurio

et al. 2024

IJN

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Introduction SOCS3 (suppressor of cytokine signaling 3) protein is a crucial regulator of cytokine-induced inflammation, and its administration has been shown to have therapeutic effects. Recently, we designed a chimeric proteomimetic of SOCS3, mimicking the interfacing regions of a ternary complex composed of SOCS3, JAK2 (Janus kinase 2) and gp130 (glycoprotein 130) proteins. The derived chimeric peptide, KIRCONG chim, demonstrated limited mimetic function owing to its poor water solubility. Methods We report investigations concerning a PEGylated variant of KIRCONG mimetic, named KIRCONG chim, bearing a PEG (Polyethylene glycol) moiety as a linker of noncontiguous SOCS3 regions. Its ability to bind to the catalytic domain of JAK2 was evaluated through MST (MicroScale Thermophoresis), as well as its stability in biological serum assays. The structural features of the cyclic compounds were investigated by CD (circular dichroism), nuclear magnetic resonance (NMR), and molecular dynamic (MD) studies. To evaluate the cellular effects, we employed a PLGA-nanoparticle as a delivery system after characterization using DLS and SEM techniques. Results KIRCONG chim PEG-revealed selective penetration into triple-negative breast cancer (TNBC) MDA-MB-231 cells with respect to the human breast epithelial cell line (MCF10A), acting as a potent inhibitor of STAT3 phosphorylation. Discussion Overall, the data indicated that miniaturization of the SOCS3 protein is a promising therapeutic approach for aberrant dysregulation of JAK/STAT during cancer progression.

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Section: Introductionmentioning

confidence: 99%