This study focuses on designing hybrid theranostic nanosystems, utilizing gadolinium-doped carbon nanodots decorated with bioreducible amphoteric polyamidoamines (PAAs). The objective is to synergize the exceptional theranostic properties of gadolinium-doped carbon nanodots (CDs) with the siRNA complexation capabilities of PAAs. Linear copolymeric polyamidoamines, based on N,N'-bis(acryloyl)cystamine, arginine, and agmatine, were synthesized, resulting in three distinct amphoteric copolymers. Notably, sulfur bridges within the PAA repeating units confer pronounced susceptibility to glutathione-mediated degradation─a key attribute in the tumor microenvironment. This pathway enables controlled and stimuli-responsive siRNA release, theoretically providing precise spatiotemporal control over therapeutic interventions. The selected PAA, conjugated with CDs using the redox-sensitive spacer cystamine, formed the CDs-Cys-PAA conjugate with superior siRNA complexing capacity. Stable against polyanion exchange, the CDs-Cys-PAA/siRNA complex released siRNA in the presence of GSH. In vitro studies assessed cytocompatibility, internalization, and gene silencing efficacy on HeLa, MCF-7, and 16HBE cell lines.

Drago, S.E., Utzeri, M.A., Mauro, N., Cavallaro, G. (2024). Polyamidoamine-Carbon Nanodot Conjugates with Bioreducible Building Blocks: Smart Theranostic Platforms for Targeted siRNA Delivery. BIOMACROMOLECULES, 25(2), 1191-1204 [10.1021/acs.biomac.3c01185].

Polyamidoamine-Carbon Nanodot Conjugates with Bioreducible Building Blocks: Smart Theranostic Platforms for Targeted siRNA Delivery

Drago, Salvatore Emanuele
Primo
;
Utzeri, Mara Andrea
Secondo
;
Mauro, Nicolò
Penultimo
;
Cavallaro, Gennara
Ultimo
2024-02-12

Abstract

This study focuses on designing hybrid theranostic nanosystems, utilizing gadolinium-doped carbon nanodots decorated with bioreducible amphoteric polyamidoamines (PAAs). The objective is to synergize the exceptional theranostic properties of gadolinium-doped carbon nanodots (CDs) with the siRNA complexation capabilities of PAAs. Linear copolymeric polyamidoamines, based on N,N'-bis(acryloyl)cystamine, arginine, and agmatine, were synthesized, resulting in three distinct amphoteric copolymers. Notably, sulfur bridges within the PAA repeating units confer pronounced susceptibility to glutathione-mediated degradation─a key attribute in the tumor microenvironment. This pathway enables controlled and stimuli-responsive siRNA release, theoretically providing precise spatiotemporal control over therapeutic interventions. The selected PAA, conjugated with CDs using the redox-sensitive spacer cystamine, formed the CDs-Cys-PAA conjugate with superior siRNA complexing capacity. Stable against polyanion exchange, the CDs-Cys-PAA/siRNA complex released siRNA in the presence of GSH. In vitro studies assessed cytocompatibility, internalization, and gene silencing efficacy on HeLa, MCF-7, and 16HBE cell lines.
12-feb-2024
Settore CHIM/09 - Farmaceutico Tecnologico Applicativo
Drago, S.E., Utzeri, M.A., Mauro, N., Cavallaro, G. (2024). Polyamidoamine-Carbon Nanodot Conjugates with Bioreducible Building Blocks: Smart Theranostic Platforms for Targeted siRNA Delivery. BIOMACROMOLECULES, 25(2), 1191-1204 [10.1021/acs.biomac.3c01185].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10447/624535
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