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用于类芬顿Mn/Fe递送的可注射水凝胶增强化学动力学疗法，可预防骨肉瘤复发并促进切除术后伤口愈合。

Injectable hydrogels for Fenton-like Mn/Fe delivery with enhanced chemodynamic therapy prevent osteosarcoma recurrence and promote wound healing after excision surgery.

作者信息

Wang Lutong, Guo Haoyu, Zhang Weiyue, Li Xingyin, Su Ziliang, Huang Xin

机构信息

Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

出版信息

Mater Today Bio. 2024 Oct 11;29:101297. doi: 10.1016/j.mtbio.2024.101297. eCollection 2024 Dec.

DOI:10.1016/j.mtbio.2024.101297
PMID:39493811
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11530760/
Abstract

Local recurrence of osteosarcoma and wound healing after excision surgery are major challenges in clinical research. The present anti-tumor treatments could inhibit normal tissues, resulting in difficulties in surgical wound healing. In this study, we constructed an injectable hydrogel as a platform to co-deliver MnO nanoparticles and ferrocene Fc, termed as (MnO/Fc)@PLGA for osteosarcoma treatment and wound healing after excision. By simple local injection, the hydrogel could form a protective barrier on the surgical wound after osteosarcoma excision, which could promote wound healing and steady release of MnO/Fc nanoparticles. The released MnO/Fc might undergo the Fenton reaction through Mn/Fe to inhibit osteosarcoma cells with chemodynamic therapy (CDT). Furthermore, MnO could catalyze endogenous HO to produce O, which eliminates the adverse effects of HO and remodels the hypoxic state in the local lesions. The increased O facilitated surgical wound healing and anti-tumor effects by regulating the hypoxia inducible factor-1 functions. In conclusion, (MnO/Fc)@PLGA hydrogel could effectively prevent local recurrence of osteosarcoma and promote wound healing after excision surgery, thereby providing a novel strategy for tumor treatment and tissue repair.

摘要

骨肉瘤的局部复发以及切除手术后的伤口愈合是临床研究中的重大挑战。目前的抗肿瘤治疗可能会抑制正常组织，导致手术伤口愈合困难。在本研究中，我们构建了一种可注射水凝胶作为平台，用于共同递送MnO纳米颗粒和二茂铁Fc，称为(MnO/Fc)@PLGA，用于骨肉瘤治疗和切除后的伤口愈合。通过简单的局部注射，水凝胶可在骨肉瘤切除后的手术伤口上形成保护屏障，促进伤口愈合并使MnO/Fc纳米颗粒稳定释放。释放的MnO/Fc可能通过Mn/Fe发生芬顿反应，以化学动力疗法(CDT)抑制骨肉瘤细胞。此外，MnO可催化内源性HO产生O，消除HO的不良影响并重塑局部病变中的缺氧状态。增加的O通过调节缺氧诱导因子-1的功能促进手术伤口愈合和抗肿瘤作用。总之，(MnO/Fc)@PLGA水凝胶可有效预防骨肉瘤的局部复发并促进切除手术后的伤口愈合，从而为肿瘤治疗和组织修复提供一种新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/854a/11530760/fdc2e341e189/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/854a/11530760/2337708cf616/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/854a/11530760/908e23268bf6/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/854a/11530760/95d8650e19d7/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/854a/11530760/e6eccc956692/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/854a/11530760/f7676649304f/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/854a/11530760/aca925777d0d/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/854a/11530760/83189836a2c3/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/854a/11530760/f6d9c05af5d5/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/854a/11530760/fdc2e341e189/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/854a/11530760/2337708cf616/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/854a/11530760/908e23268bf6/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/854a/11530760/95d8650e19d7/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/854a/11530760/e6eccc956692/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/854a/11530760/f7676649304f/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/854a/11530760/aca925777d0d/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/854a/11530760/83189836a2c3/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/854a/11530760/f6d9c05af5d5/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/854a/11530760/fdc2e341e189/gr8.jpg

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本文引用的文献

[1]
Nanocatalytic theranostics with intracellular mutual promotion for ferroptosis and chemo-photothermal therapy.

J Colloid Interface Sci. 2024-3

[2]
Overcoming T Cell Exhaustion in Tumor Microenvironment via Immune Checkpoint Modulation with Nano-Delivery Systems for Enhanced Immunotherapy.

Small Methods. 2024-8

[3]
Bioinspired nanovesicles released from injectable hydrogels facilitate diabetic wound healing by regulating macrophage polarization and endothelial cell dysfunction.

J Nanobiotechnology. 2023-10-3

[4]
Injectable, antibacterial, and oxygen-releasing chitosan-based hydrogel for multimodal healing of bacteria-infected wounds.

J Mater Chem B. 2023-8-24

[5]
Osteosarcoma.

Nat Rev Dis Primers. 2022-12-8

[6]
Dapagliflozin-Loaded Exosome Mimetics Facilitate Diabetic Wound Healing by HIF-1α-Mediated Enhancement of Angiogenesis.

Adv Healthc Mater. 2023-3

[7]
Macrophage membrane-coated nanovesicles for dual-targeted drug delivery to inhibit tumor and induce macrophage polarization.

Bioact Mater. 2022-11-9

[8]
Tumor Microenvironment-Adaptive Nanoplatform Synergistically Enhances Cascaded Chemodynamic Therapy.

Bioact Mater. 2022-10-7

[9]
Thermosensitive vancomycin@PLGA-PEG-PLGA/HA hydrogel as an all-in-one treatment for osteomyelitis.

Int J Pharm. 2022-11-5

[10]
Single-cell transcriptomics reveals the regulative roles of cancer associated fibroblasts in tumor immune microenvironment of recurrent osteosarcoma.

Theranostics. 2022

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