Urea immunoliposome inhibits human vascular endothelial cell proliferation for hemangioma treatment

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WORLD JOURNAL OF SURGICAL ONCOLOGY

RESEARCH

Open Access

Urea immunoliposome inhibits human vascular endothelial cell proliferation for hemangioma treatment Zhiliang Wang, Jie Li, Xin Xu, Xianglong Duan and Gang Cao*

Abstract Background: Urea injection has been used in hemangioma treatment as sclerotherapy. It shrinks vascular endothelial cells and induces degeneration, necrosis, and fibrosis. However, this treatment still has disadvantages, such as lacking targeting and difficulty in controlling the urea dosage. Thus, we designed a urea immunoliposome to improve the efficiency of treatment. Methods: The urea liposome was prepared by reverse phase evaporation. Furthermore, the urea immunoliposome was generated by coupling the urea liposome with a vascular endothelial growth factor receptor (VEGFR) monoclonal antibody using the glutaraldehyde cross-linking method. The influence of the urea immunoliposome on cultured human hemangioma vascular endothelial cells was observed preliminarily. Results: Urea immunoliposomes showed typical liposome morphology under a transmission electron microscope, with an encapsulation percentage of 54.4% and a coupling rate of 36.84% for anti-VEGFR. Treatment with the urea immunoliposome significantly inhibited the proliferation of hemangioma vascular endothelial cells (HVECs) in a time- and dose-dependent manner. Conclusions: The urea immunoliposome that we developed distinctly and persistently inhibited the proliferation of HVECs and is expected to be used in clinical hemangioma treatment. Keywords: Anti-VEGFR, HVECs, Hemangioma, Immunoliposome, Targeted therapy, Urea

Background Hemangioma is the most common benign tumor of infancy and is characterized by vascular endothelial cell proliferation. Because its predilection sites are always on the body surface, especially in the maxillofacial region, hemangioma seriously affects patients’ appearance and physiological function, and even induces mental stress and psychological disorders [1,2]. Urea injection has long been used in the treatment of hemangioma in our hospital as a type of sclerotherapy, particularly in refractory and recurrent cases [3-5]. Urea can shrink hemangioma endothelial cells to induce degeneration, necrosis, and fibrosis. This treatment has shown obvious therapeutic effects, even cures. However, it still presents several disadvantages: urea injection is not targeted, and its dosage * Correspondence: [email protected] Department of General Surgery, The Second Affiliated Hospital of Medical College, Xi’an Jiaotong University, Xi’an 710004, China

is difficult to control: too high a dose would induce local necrosis, ulceration, and infection, ultimately inducing scars and developmental disorders; too low a dose would not induce an obvious effect and would prolong the treatment cycle. Inappropriately high local urea doses have also induced other complications [3]. Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) have been reported to be crucial in vasculogenesis and angiogenesis. They are closely rela