Self-propelled nanomotor reconstructs tumor microenvironment through synergistic hypoxia alleviation and glycolysis inhibition for promoted anti-metastasis
Solid tumors always exhibit local hypoxia, resulting in the high metastasis and inertness to chemotherapy. Reconstruction of hypoxic tumor microenvironment (TME) is considered a potential therapy compared to directly killing tumor cells. However, the insufficient oxygen delivery to deep tumor and th...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-09-01
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| Series: | Acta Pharmaceutica Sinica B |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383521001337 |
| _version_ | 1818736626510069760 |
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| author | Wenqi Yu Ruyi Lin Xueqin He Xiaotong Yang Huilin Zhang Chuan Hu Rui Liu Yuan Huang Yi Qin Huile Gao |
| author_facet | Wenqi Yu Ruyi Lin Xueqin He Xiaotong Yang Huilin Zhang Chuan Hu Rui Liu Yuan Huang Yi Qin Huile Gao |
| author_sort | Wenqi Yu |
| collection | DOAJ |
| description | Solid tumors always exhibit local hypoxia, resulting in the high metastasis and inertness to chemotherapy. Reconstruction of hypoxic tumor microenvironment (TME) is considered a potential therapy compared to directly killing tumor cells. However, the insufficient oxygen delivery to deep tumor and the confronting “Warburg effect” compromise the efficacy of hypoxia alleviation. Herein, we construct a cascade enzyme-powered nanomotor (NM-si), which can simultaneously provide sufficient oxygen in deep tumor and inhibit the aerobic glycolysis to potentiate anti-metastasis in chemotherapy. Catalase (Cat) and glucose oxidase (GOx) are co-adsorbed on our previously reported CAuNCs@HA to form self-propelled nanomotor (NM), with hexokinase-2 (HK-2) siRNA further condensed (NM-si). The persistent production of oxygen bubbles from the cascade enzymatic reaction propels NM-si to move forward autonomously and in a controllable direction along H2O2 gradient towards deep tumor, with hypoxia successfully alleviated in the meantime. The autonomous movement also facilitates NM-si with lysosome escaping for efficient HK-2 knockdown to inhibit glycolysis. In vivo results demonstrated a promising anti-metastasis effect of commercially available albumin-bound paclitaxel (PTX@HSA) after pre-treated with NM-si for TME reconstruction. This cascade enzyme-powered nanomotor provides a potential prospect in reversing the hypoxic TME and metabolic pathway for reinforced anti-metastasis of chemotherapy. |
| first_indexed | 2024-12-18T00:40:08Z |
| format | Article |
| id | doaj.art-6acda917ecbe40428fe0f5eb28f7f50c |
| institution | Directory Open Access Journal |
| issn | 2211-3835 |
| language | English |
| last_indexed | 2024-12-18T00:40:08Z |
| publishDate | 2021-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj.art-6acda917ecbe40428fe0f5eb28f7f50c2022-12-21T21:26:54ZengElsevierActa Pharmaceutica Sinica B2211-38352021-09-0111929242936Self-propelled nanomotor reconstructs tumor microenvironment through synergistic hypoxia alleviation and glycolysis inhibition for promoted anti-metastasisWenqi Yu0Ruyi Lin1Xueqin He2Xiaotong Yang3Huilin Zhang4Chuan Hu5Rui Liu6Yuan Huang7Yi Qin8Huile Gao9Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, ChinaKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, ChinaKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, ChinaKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, ChinaKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, ChinaKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, ChinaKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, ChinaKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, ChinaDepartment of Orthopedics, Zhuhai Hospital, Jinan University, Zhuhai People's Hospital, Guangdong 519000, China; Corresponding authors.Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China; Corresponding authors.Solid tumors always exhibit local hypoxia, resulting in the high metastasis and inertness to chemotherapy. Reconstruction of hypoxic tumor microenvironment (TME) is considered a potential therapy compared to directly killing tumor cells. However, the insufficient oxygen delivery to deep tumor and the confronting “Warburg effect” compromise the efficacy of hypoxia alleviation. Herein, we construct a cascade enzyme-powered nanomotor (NM-si), which can simultaneously provide sufficient oxygen in deep tumor and inhibit the aerobic glycolysis to potentiate anti-metastasis in chemotherapy. Catalase (Cat) and glucose oxidase (GOx) are co-adsorbed on our previously reported CAuNCs@HA to form self-propelled nanomotor (NM), with hexokinase-2 (HK-2) siRNA further condensed (NM-si). The persistent production of oxygen bubbles from the cascade enzymatic reaction propels NM-si to move forward autonomously and in a controllable direction along H2O2 gradient towards deep tumor, with hypoxia successfully alleviated in the meantime. The autonomous movement also facilitates NM-si with lysosome escaping for efficient HK-2 knockdown to inhibit glycolysis. In vivo results demonstrated a promising anti-metastasis effect of commercially available albumin-bound paclitaxel (PTX@HSA) after pre-treated with NM-si for TME reconstruction. This cascade enzyme-powered nanomotor provides a potential prospect in reversing the hypoxic TME and metabolic pathway for reinforced anti-metastasis of chemotherapy.http://www.sciencedirect.com/science/article/pii/S2211383521001337NanomotorMicroenvironment modulationHypoxiaAerobic glycolysisTriple negative breast cancerAnti-metastasis |
| spellingShingle | Wenqi Yu Ruyi Lin Xueqin He Xiaotong Yang Huilin Zhang Chuan Hu Rui Liu Yuan Huang Yi Qin Huile Gao Self-propelled nanomotor reconstructs tumor microenvironment through synergistic hypoxia alleviation and glycolysis inhibition for promoted anti-metastasis Acta Pharmaceutica Sinica B Nanomotor Microenvironment modulation Hypoxia Aerobic glycolysis Triple negative breast cancer Anti-metastasis |
| title | Self-propelled nanomotor reconstructs tumor microenvironment through synergistic hypoxia alleviation and glycolysis inhibition for promoted anti-metastasis |
| title_full | Self-propelled nanomotor reconstructs tumor microenvironment through synergistic hypoxia alleviation and glycolysis inhibition for promoted anti-metastasis |
| title_fullStr | Self-propelled nanomotor reconstructs tumor microenvironment through synergistic hypoxia alleviation and glycolysis inhibition for promoted anti-metastasis |
| title_full_unstemmed | Self-propelled nanomotor reconstructs tumor microenvironment through synergistic hypoxia alleviation and glycolysis inhibition for promoted anti-metastasis |
| title_short | Self-propelled nanomotor reconstructs tumor microenvironment through synergistic hypoxia alleviation and glycolysis inhibition for promoted anti-metastasis |
| title_sort | self propelled nanomotor reconstructs tumor microenvironment through synergistic hypoxia alleviation and glycolysis inhibition for promoted anti metastasis |
| topic | Nanomotor Microenvironment modulation Hypoxia Aerobic glycolysis Triple negative breast cancer Anti-metastasis |
| url | http://www.sciencedirect.com/science/article/pii/S2211383521001337 |
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