Abstract
The most common tumors in children are infantile hemangiomas which could cause morbidity and severe complications. The development of novel alternative drugs to treat infantile hemangiomas is necessary, since Hemangeol is the only US Food and Drug Administration-approved drug for infantile hemangiomas. However, Hemangeol has several disadvantages, including a high frequency of administration and adverse effects. Rapamycin is a well‑established antiangiogenic drug, and we have previously developed rapamycin lipid polymer nanoparticles (R‑PLNPs) as a local sustained‑release drug delivery system to achieve controlled rapamycin release and to decrease the frequency of administration and side effects of rapamycin. To improve the targeting of R‑PLNPs to infantile hemangiomas in the present study, R‑PLNPs were modified to include an antibody against vascular endothelial growth factor receptor (VEGF). The characteristics, and the anti‑hemangioma activity of the resulting R‑PLNPs coupled with the anti‑VEGFR2 antibody (named R‑PLNPs‑V) were examined invitro and invivo. R‑PLNPs‑V possessed a small size (115nm) and sustained drug release for 6days. The anti‑VEGFR2 antibody promoted the targeting and cytotoxic effect of R‑PLNPs‑V to human hemangioma endothelial cells and human umbilical vein endothelial cells. Using a subcutaneous infantile hemangioma xenograft in mice, the invivo therapeutic effect (evaluated with hemangioma weight, volume, and microvessel density) of R‑PLNPs‑V was demonstrated to be superior compared with rapamycin alone and other non‑targeted nanoparticles, without any total body weight loss. In summary, R‑PLNPs‑V could facilitate targeted delivery and sustained release of rapamycin to infantile hemangiomas, and thus may represent a promising candidate treatment for infantile hemangiomas.
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