A novel therapeutic approach to hemangiomas: Combining photothermal therapy and ferroptosis in a microneedle delivery system

Infantile Hemangioma (IH) is the most common benign vascular tumor occurred in infants and young children. The larger hemangiomas or lesions located in specific areas can cause severe complications, such as disfigurement, obstruction, or ulceration, increasing the risk of functional impairment. Prop...

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Main Authors: Yiming Geng, Cancan Meng, Hanzhi Zhang, Chuan Ma, Xiao Fu, Haiwei Wu
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Materials Today Bio
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Online Access:http://www.sciencedirect.com/science/article/pii/S2590006425003072
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author Yiming Geng
Cancan Meng
Hanzhi Zhang
Chuan Ma
Xiao Fu
Haiwei Wu
author_facet Yiming Geng
Cancan Meng
Hanzhi Zhang
Chuan Ma
Xiao Fu
Haiwei Wu
author_sort Yiming Geng
collection DOAJ
description Infantile Hemangioma (IH) is the most common benign vascular tumor occurred in infants and young children. The larger hemangiomas or lesions located in specific areas can cause severe complications, such as disfigurement, obstruction, or ulceration, increasing the risk of functional impairment. Propranolol, serving as the first‐line drug for IH treatment, still poses various challenges. Certain patients exhibit low sensitivity to propranolol therapy or face recurrence, which become the leading reason for the failure of IH treatment. Additionally, the requirement for frequent daily medication can also complicate adherence for patients. Hence, developing novel IH therapy methods or drug administration routes is significantly important to enhance therapeutic effect and reduce side effects. Accordingly, in this study, we introduced an innovative photothermal, dissolving microneedles (MNs) patch designed specifically for IH therapy. Firstly, a pH responsive self-assembly nanoplatform with photothermal effect is designed by encapsulating propranolol (PRN) into zeolitic imidazolate framework-8 (ZIF-8) NPs and modifying with TA/Fe nanocomplexes. The fabricated PRN@ZIF-8@TA/Fe (PZ@TA/Fe) NPs exhibited good biocompatibility, pH-responsive degradation, photothermal conversion efficiency inside hemangioma endothelial cells (HemECs). Importantly, TA/Fe surface modification led to intracellular iron overload, which subsequently induced the Fenton reaction and triggered ferroptosis process. The combination of photothermal therapy and ferroptosis therapy exhibited a superior synergistic effect in damaging HemECs and vascular structures. The PZ@TA/Fe NPs loaded in MNs patch further ensured targeted delivery to lesion areas and achieved precise and maximal release of the PZ@TA/Fe NPs, while reducing systemic side effects to normal vasculature or tissue. The PZ@TA/Fe@MNs showed remarkable anti-angiogenic effect against IH in mice model. This study first investigates the potential of ferroptosis therapy in IH treatment, and highlights the substantial therapeutic effect of combining photothermal therapy and ferroptosis effects against IH proliferation. This approach can also become a more effective and safer treatment method for other diseases characterized by abnormal angiogenesis.
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spelling doaj-art-5400c2b49346449ea0716142b4f8e10e2025-08-20T02:12:08ZengElsevierMaterials Today Bio2590-00642025-06-013210174810.1016/j.mtbio.2025.101748A novel therapeutic approach to hemangiomas: Combining photothermal therapy and ferroptosis in a microneedle delivery systemYiming Geng0Cancan Meng1Hanzhi Zhang2Chuan Ma3Xiao Fu4Haiwei Wu5Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, ChinaDepartment of Oral and Maxillofacial Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, ChinaDepartment of Oral and Maxillofacial Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China; School of Stomatology, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, ChinaDepartment of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, China; Corresponding author. Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, China, No.44-1 Wenhua Road West, 250012, Jinan, Shandong, China.Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China; School of Stomatology, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, China; Corresponding author. Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwu Road, Jinan, 250021, China.Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China; Corresponding author. Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwu Road, Jinan, 250021, China.Infantile Hemangioma (IH) is the most common benign vascular tumor occurred in infants and young children. The larger hemangiomas or lesions located in specific areas can cause severe complications, such as disfigurement, obstruction, or ulceration, increasing the risk of functional impairment. Propranolol, serving as the first‐line drug for IH treatment, still poses various challenges. Certain patients exhibit low sensitivity to propranolol therapy or face recurrence, which become the leading reason for the failure of IH treatment. Additionally, the requirement for frequent daily medication can also complicate adherence for patients. Hence, developing novel IH therapy methods or drug administration routes is significantly important to enhance therapeutic effect and reduce side effects. Accordingly, in this study, we introduced an innovative photothermal, dissolving microneedles (MNs) patch designed specifically for IH therapy. Firstly, a pH responsive self-assembly nanoplatform with photothermal effect is designed by encapsulating propranolol (PRN) into zeolitic imidazolate framework-8 (ZIF-8) NPs and modifying with TA/Fe nanocomplexes. The fabricated PRN@ZIF-8@TA/Fe (PZ@TA/Fe) NPs exhibited good biocompatibility, pH-responsive degradation, photothermal conversion efficiency inside hemangioma endothelial cells (HemECs). Importantly, TA/Fe surface modification led to intracellular iron overload, which subsequently induced the Fenton reaction and triggered ferroptosis process. The combination of photothermal therapy and ferroptosis therapy exhibited a superior synergistic effect in damaging HemECs and vascular structures. The PZ@TA/Fe NPs loaded in MNs patch further ensured targeted delivery to lesion areas and achieved precise and maximal release of the PZ@TA/Fe NPs, while reducing systemic side effects to normal vasculature or tissue. The PZ@TA/Fe@MNs showed remarkable anti-angiogenic effect against IH in mice model. This study first investigates the potential of ferroptosis therapy in IH treatment, and highlights the substantial therapeutic effect of combining photothermal therapy and ferroptosis effects against IH proliferation. This approach can also become a more effective and safer treatment method for other diseases characterized by abnormal angiogenesis.http://www.sciencedirect.com/science/article/pii/S2590006425003072HemangiomaAnti-angiogenesisMicroneedle patchFerroptosis therapyPhotothermal effect
spellingShingle Yiming Geng
Cancan Meng
Hanzhi Zhang
Chuan Ma
Xiao Fu
Haiwei Wu
A novel therapeutic approach to hemangiomas: Combining photothermal therapy and ferroptosis in a microneedle delivery system
Materials Today Bio
Hemangioma
Anti-angiogenesis
Microneedle patch
Ferroptosis therapy
Photothermal effect
title A novel therapeutic approach to hemangiomas: Combining photothermal therapy and ferroptosis in a microneedle delivery system
title_full A novel therapeutic approach to hemangiomas: Combining photothermal therapy and ferroptosis in a microneedle delivery system
title_fullStr A novel therapeutic approach to hemangiomas: Combining photothermal therapy and ferroptosis in a microneedle delivery system
title_full_unstemmed A novel therapeutic approach to hemangiomas: Combining photothermal therapy and ferroptosis in a microneedle delivery system
title_short A novel therapeutic approach to hemangiomas: Combining photothermal therapy and ferroptosis in a microneedle delivery system
title_sort novel therapeutic approach to hemangiomas combining photothermal therapy and ferroptosis in a microneedle delivery system
topic Hemangioma
Anti-angiogenesis
Microneedle patch
Ferroptosis therapy
Photothermal effect
url http://www.sciencedirect.com/science/article/pii/S2590006425003072
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