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...
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2021-09-01T00:00:00Z.
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LEADER | 00000 am a22000003u 4500 | ||
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001 | doaj_6acda917ecbe40428fe0f5eb28f7f50c | ||
042 | |a dc | ||
100 | 1 | 0 | |a Wenqi Yu |e author |
700 | 1 | 0 | |a Ruyi Lin |e author |
700 | 1 | 0 | |a Xueqin He |e author |
700 | 1 | 0 | |a Xiaotong Yang |e author |
700 | 1 | 0 | |a Huilin Zhang |e author |
700 | 1 | 0 | |a Chuan Hu |e author |
700 | 1 | 0 | |a Rui Liu |e author |
700 | 1 | 0 | |a Yuan Huang |e author |
700 | 1 | 0 | |a Yi Qin |e author |
700 | 1 | 0 | |a Huile Gao |e author |
245 | 0 | 0 | |a Self-propelled nanomotor reconstructs tumor microenvironment through synergistic hypoxia alleviation and glycolysis inhibition for promoted anti-metastasis |
260 | |b Elsevier, |c 2021-09-01T00:00:00Z. | ||
500 | |a 2211-3835 | ||
500 | |a 10.1016/j.apsb.2021.04.006 | ||
520 | |a 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. | ||
546 | |a EN | ||
690 | |a Nanomotor | ||
690 | |a Microenvironment modulation | ||
690 | |a Hypoxia | ||
690 | |a Aerobic glycolysis | ||
690 | |a Triple negative breast cancer | ||
690 | |a Anti-metastasis | ||
690 | |a Therapeutics. Pharmacology | ||
690 | |a RM1-950 | ||
655 | 7 | |a article |2 local | |
786 | 0 | |n Acta Pharmaceutica Sinica B, Vol 11, Iss 9, Pp 2924-2936 (2021) | |
787 | 0 | |n http://www.sciencedirect.com/science/article/pii/S2211383521001337 | |
787 | 0 | |n https://doaj.org/toc/2211-3835 | |
856 | 4 | 1 | |u https://doaj.org/article/6acda917ecbe40428fe0f5eb28f7f50c |z Connect to this object online. |