Hyperbranched polymer drug delivery treatment for lung metastasis of salivary adenoid cystic carcinoma in nude mice

Abstract Salivary adenoid cystic carcinoma (SACC) is associated with a high rate of lung metastasis. When lung metastasis occurs, the effects of traditional chemotherapy on SACC are poor. Hyperbranched polymer drug delivery (degradable hyperbranched polyglycerols, dHPGs) can be used as a strategy to load several drugs, and obtain beneficial effects on SACC lung metastasis through enhanced permeability and retention. In the present study, hydroxycamptothecin (HPT)-conjugated dHPG (dHPG-HPT) was synthesized and its effects on SACC xenografts in the lungs of nude mice were evaluated. SACC cells with a high potential for pulmonary metastasis (SACC-LM cells) were injected into the tail vein of mice, establishing a nude mouse model. The mice were randomly divided into the three following groups: Control, HPT and dHPG-HPT. Saline (control), HPT or dHPG-HPT were injected into the mice. After two weeks, the mice were euthanized and their lungs were removed. The lungs were paraffin-embedded for hematoxylin and eosin, and immunohistochemical staining analyses. Primary antibodies directed against vascular endothelial growth factor (VEGF), cluster of differentiation 34 (CD34), proliferating cell nuclear antigen (PCNA) and matrix metalloproteinase 9 (MMP9) were used. Gross observation demonstrated that the volumes of SACC lung metastasis nodules were significantly decreased in the dHPG-HPT group compared with the control and HPT groups. Immunohistochemical analysis revealed a lower expression of VEGF, CD34, PCNA and MMP9 in the dHPG-HPT group. The results of the current study suggest that dHPG-HPT can suppress the growth of SACC xenografts in nude mice, providing a theoretical basis for macromolecular drug delivery-based treatment of SACC. Keywords: EPR effect, hyperbranched polymers, lung metastasis, salivary adenoid cystic carcinoma