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ACS Nano

ACS Nano

IF: 15.8
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Metabolic Nanoregulators Induce Ferroptosis and Change Metabolite Flow to Reverse Immunosuppressive Tumor Microenvironment

Published:12 December 2024 DOI: 10.1021/acsnano.4c13425
Yu Wang, Qinjun Chen, Yifan Luo, Yangqi Qu, Xuwen Li, Haolin Song, Chufeng Li, Yiwen Zhang, Tao Sun, Chen Jiang

Abstract

Aberrant energy and substance metabolic pathways of tumor cells critically support tumor cell proliferation by hijacking the resources from nonmalignant cells, thereby establishing a metabolite flow favorable to tumor progression. This metabolic adaptation of tumor cells further modulates the immune landscape, ultimately creating a tumor microenvironment characterized by drug resistance and immunosuppression. The synergistic regulation of energy and substance metabolic pathways might be a good antitumor therapeutic paradigm. However, due to the metabolic convergence, it is crucial to selectively modulate the aberrant metabolism of tumor cells without compromising the functionality of other cells. Small-molecule drugs have the ability to target a wide range of biomolecules for antitumor therapy, but their application is limited by undesirable toxicities. Constructing nanodrug delivery systems can improve their properties and allow for the inclusion of multiple drugs, thereby exerting synergistic antitumor effects. In this study, we developed a two-drug codelivery system using drugs-conjugated multibranched polymers to modulate tumor cell metabolism by exploiting synthetic lethal pathways for safe and effective antitumor therapy. By delivery of adapalene and erastin simultaneously through nanoparticles, the material and energy metabolism of tumor cells can be regulated. This nanoparticle construction achieves tumor tissue targeting and responsive drug release, alters metabolite flow within tumor cells, and effectively kills tumor cells. Additionally, the nanoparticles can reverse the tumor immunosuppressive microenvironment, starting from single-cell regulation to whole-lesion control.

Substances (9)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Ascorbic Acid 50-81-7 C6H8O6 1630 suppliers $6.00-$2170.00
Ethylene glycol 107-21-1 C2H6O2 1403 suppliers $10.00-$908.54
Potassium carbonate 584-08-7 K2CO3 1286 suppliers $5.00-$7200.00
4-Dimethylaminopyridine 1122-58-3 C7H10N2 1240 suppliers $6.00-$5370.00
Pyridine 110-86-1 C5H5N 930 suppliers $9.00-$16860.00
Colchicine 64-86-8 C22H25NO6 729 suppliers $16.00-$3980.00
Adapalene 106685-40-9 C28H28O3 699 suppliers $6.00-$1504.50
2-[1-[4-[2-(4-Chlorophenoxy)acetyl]-1-piperazinyl]ethyl]-3-(2-ethoxyphenyl)-4(3H)-Quinazolinone 571203-78-6 C30H31ClN4O4 158 suppliers $44.00-$2691.10
1,1'-DIOCTADECYL-3,3,3',3'-TETRAMETHYLINDODICARBOCYANINE PERCHLORATE 127274-91-3 C61H99ClN2O4 85 suppliers $37.00-$600.00

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