Unraveling mechanism and enhancing selectivity of a RuII‐bis‐bipyridyl‐morphocumin complex with RAFT‐generated glycopolymer exploiting Warburg effect in cancer DOI
Arindam Mukherjee, Souryadip Roy, Soumya Paul

et al.

Chemistry - A European Journal, Journal Year: 2024, Volume and Issue: 31(8)

Published: Nov. 30, 2024

The Warburg effect, which generates increased demand of glucose in cancer cells is a relatively underexplored phenomenon existing commercial drugs to enhance uptake cells. Here, we present chemotherapeutic strategy employing Ru(II)-bis-bipyridyl-morphocumin complex (2) encapsulated self-assembling glucose-functionalized copolymer P(G-EMA-co-MMA) (where G=glucose; MMA=methyl methacrylate; EMA=ethyl methacrylate), designed exploit this effect for enhanced selectivity treatment. polymer, synthesized via reversible-addition fragmentation chain transfer (RAFT) polymerization, has number average molecular weight (Mn,NMR) 8000 g/mol. Complex 2, stable aqueous media, selectively releases cytotoxic, lysosome-targeting compound, morphocumin, the presence excess hydrogen peroxide (H₂O₂), reactive oxygen species (ROS) prevalent tumor microenvironments. Additionally, 2 promotes ROS accumulation, may further morphocumin release through synergistic domino effect. Comparative studies reveal that outperforms its curcumin Ru(II) (1) analog solution stability, organelle specificity, and cellular mechanisms. Both 1 exhibit phototherapeutic effects under low-intensity visible light, but their chemotoxicity significantly increases with incubation time dark, highlighting superior efficacy O,O-coordinating ternary polypyridyl complexes. induces apoptosis intrinsic pathway shows 9-fold increase pancreatic (MIA PaCa-2) over non-cancerous HEK293 when glucose-conjugated polymer (DP@2). Glucose deprivation culture medium enhances drug by an additional 5-fold. This work underscores potential polymers ROS-responsive complexes targeted therapy.

Language: Английский

Designing Nano-Hemin for Ferroptosis-Mediated Cell Death via Enzymatic Hemin Digestion DOI
Abu Raihan Sarkar,

Nayana Mukherjee,

Ankan Kumar Sarkar

et al.

ACS Applied Materials & Interfaces, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 18, 2024

Hemin is a protoporphyrin complex of ferric ion which catalyzes H

Language: Английский

Citations

0
Precision-engineered PROTACs minimize off-tissue effects in cancer therapy DOI Creative Commons

Jianghua Shi,

Luo Wang,

Xuanwei Zeng

et al.

Frontiers in Molecular Biosciences, Journal Year: 2024, Volume and Issue: 11

Published: Nov. 22, 2024

Proteolysis-targeting chimeras (PROTACs) offer a groundbreaking approach to selectively degrade disease-related proteins by utilizing the ubiquitin-proteasome system. While this strategy shows great potential in preclinical and clinical settings, off-tissue effects remain major challenge, leading toxicity healthy tissues. This review explores recent advancements aimed at improving PROTAC specificity, including tumor-specific ligand-directed PROTACs, pro-PROTACs activated tumor environments, E3 ligase overexpression strategies. Innovations such as PEGylation nanotechnology also play role optimizing efficacy. These developments hold promise for safer, more effective cancer therapies, though challenges translation.

Language: Английский

Citations

0
Unraveling mechanism and enhancing selectivity of a RuII‐bis‐bipyridyl‐morphocumin complex with RAFT‐generated glycopolymer exploiting Warburg effect in cancer DOI
Arindam Mukherjee, Souryadip Roy, Soumya Paul

et al.

Chemistry - A European Journal, Journal Year: 2024, Volume and Issue: 31(8)

Published: Nov. 30, 2024

The Warburg effect, which generates increased demand of glucose in cancer cells is a relatively underexplored phenomenon existing commercial drugs to enhance uptake cells. Here, we present chemotherapeutic strategy employing Ru(II)-bis-bipyridyl-morphocumin complex (2) encapsulated self-assembling glucose-functionalized copolymer P(G-EMA-co-MMA) (where G=glucose; MMA=methyl methacrylate; EMA=ethyl methacrylate), designed exploit this effect for enhanced selectivity treatment. polymer, synthesized via reversible-addition fragmentation chain transfer (RAFT) polymerization, has number average molecular weight (Mn,NMR) 8000 g/mol. Complex 2, stable aqueous media, selectively releases cytotoxic, lysosome-targeting compound, morphocumin, the presence excess hydrogen peroxide (H₂O₂), reactive oxygen species (ROS) prevalent tumor microenvironments. Additionally, 2 promotes ROS accumulation, may further morphocumin release through synergistic domino effect. Comparative studies reveal that outperforms its curcumin Ru(II) (1) analog solution stability, organelle specificity, and cellular mechanisms. Both 1 exhibit phototherapeutic effects under low-intensity visible light, but their chemotoxicity significantly increases with incubation time dark, highlighting superior efficacy O,O-coordinating ternary polypyridyl complexes. induces apoptosis intrinsic pathway shows 9-fold increase pancreatic (MIA PaCa-2) over non-cancerous HEK293 when glucose-conjugated polymer (DP@2). Glucose deprivation culture medium enhances drug by an additional 5-fold. This work underscores potential polymers ROS-responsive complexes targeted therapy.

Language: Английский

Citations

0