Co-Delivery of Metabolic Modulators Leads to Simultaneous Lactate Metabolism Inhibition and Intracellular Acidification for Synergistic Cancer Therapy

Co-Delivery of Metabolic Modulators Leads to Simultaneous Lactate Metabolism Inhibition and Intracellular Acidification for Synergistic Cancer Therapy

© 2023 Wiley-VCH GmbH.

Bibliographische Detailangaben
Veröffentlicht in:Advanced materials (Deerfield Beach, Fla.). - 1998. - 35(2023), 46 vom: 27. Nov., Seite e2305512
1. Verfasser: Lee, Bowon (VerfasserIn)
Weitere Verfasser: Park, Ok Kyu, Pan, Limin, Kim, Kang, Kang, Taegyu, Kim, Hyunjoong, Lee, Nohyun, Choi, Seung Hong, Hyeon, Taeghwan
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2023
Zugriff auf das übergeordnete Werk:Advanced materials (Deerfield Beach, Fla.)
Schlagworte:Journal Article ATP depletion cancer treatment combination therapy lactate metabolism large-pore mesoporous silica nanoparticles metabolic therapy Glucose Oxidase EC 1.1.3.4 Monocarboxylic Acid Transporters mehr... Glucose IY9XDZ35W2 Adenosine Triphosphate 8L70Q75FXE Albumins Silicon Dioxide 7631-86-9 Drug Carriers
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520 |a Simultaneous lactate metabolism inhibition and intracellular acidification (LIIA) is a promising approach for inducing tumor regression by depleting ATP. However, given the limited efficacy of individual metabolic modulators, a combination of various modulators is required for highly efficient LIIA. Herein, a co-delivery system that combines lactate transporter inhibitor, glucose oxidase, and O2 -evolving nanoparticles is proposed. As a vehicle, a facile room-temperature synthetic method for large-pore mesoporous silica nanoparticles (L-MSNs) is developed. O2 -evolving nanoparticles are then conjugated onto L-MSNs, followed by immobilizing the lactate transporter inhibitor and glucose oxidase inside the pores of L-MSNs. To load the lactate transporter inhibitor, which is too small to be directly loaded into the large pores, it is encapsulated in albumin by controlling the albumin conformation before being loaded into L-MSNs. Notably, inhibiting lactate efflux shifts the glucose consumption mechanism from lactate metabolism to glucose oxidase reaction, which eliminates glucose and produces acid. This leads to synergistic LIIA and subsequent ATP depletion in cancer cells. Consequently, L-MSN-based co-delivery of modulators for LIIA shows high anticancer efficacy in several mouse tumor models without toxicity in normal tissues. This study provides new insights into co-delivery of small-molecule drugs, proteins, and nanoparticles for synergistic metabolic modulation in tumors 
650 4 |a Journal Article 
650 4 |a ATP depletion 
650 4 |a cancer treatment 
650 4 |a combination therapy 
650 4 |a lactate metabolism 
650 4 |a large-pore mesoporous silica nanoparticles 
650 4 |a metabolic therapy 
650 7 |a Glucose Oxidase  |2 NLM 
650 7 |a EC 1.1.3.4  |2 NLM 
650 7 |a Monocarboxylic Acid Transporters  |2 NLM 
650 7 |a Glucose  |2 NLM 
650 7 |a IY9XDZ35W2  |2 NLM 
650 7 |a Adenosine Triphosphate  |2 NLM 
650 7 |a 8L70Q75FXE  |2 NLM 
650 7 |a Albumins  |2 NLM 
650 7 |a Silicon Dioxide  |2 NLM 
650 7 |a 7631-86-9  |2 NLM 
650 7 |a Drug Carriers  |2 NLM 
700 1 |a Park, Ok Kyu  |e verfasserin  |4 aut 
700 1 |a Pan, Limin  |e verfasserin  |4 aut 
700 1 |a Kim, Kang  |e verfasserin  |4 aut 
700 1 |a Kang, Taegyu  |e verfasserin  |4 aut 
700 1 |a Kim, Hyunjoong  |e verfasserin  |4 aut 
700 1 |a Lee, Nohyun  |e verfasserin  |4 aut 
700 1 |a Choi, Seung Hong  |e verfasserin  |4 aut 
700 1 |a Hyeon, Taeghwan  |e verfasserin  |4 aut 
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773 1 8 |g volume:35  |g year:2023  |g number:46  |g day:27  |g month:11  |g pages:e2305512 
856 4 0 |u http://dx.doi.org/10.1002/adma.202305512  |3 Volltext 
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