靶向溶瘤、化疗和DC疫苗是有应用前景的肿瘤治疗策略。我们从热带内生真菌提取了乙酰基细胞松弛素D(aCD)并将其包裹于PEG脂质体，发现aCD位于非水性脂膜内层并有肿瘤靶向治疗活性，可以有效避免aCD的毒副作用。在此基础上，本研究利用病毒拯救技术将DC趋化因子MIP-3α构建于溶瘤作用的单纯疱疹病毒1(HSV1)中，获得重组HSV1-MIP3α病毒，使该重组病毒保留HSV1溶瘤特性的同时还具有分泌MIP-3α的作用。此后将重组病毒HSV1-MIP3α(位于水溶部位)连同aCD（位于内脂膜层）同时包裹于空间结构稳定的PEG脂质体中并与肿瘤血管生成相关的endoglin单抗(aEND)共轭偶合。通过PEG脂质体同时将aEND/aCD/HSV1/MIP3α结合于一体，这种脂质体作为药物就可能同时具有靶向、溶瘤、化疗和DC体内疫苗的多种功能活性。进行体内外实验研究其功能特性以及治疗肿瘤的作用和机理。

Many approaches have been well studied and accepted as potential strategies for treatment of cancers, including tumor target therapy, oncolytic therapy, chemotherapy, anti-angeogenesis and in vivo DC vaccine. Our research group has isolated an acetyl cytochalasin D(aCD) from a tropical plant Cephalotaxus hainanensis Li, which possess better cytotoxic effects than the conventional cytochalasin D. We have encapsulated aCD in the nonaqueous interior of PEG liposomes and proved this encapsulation has tumor-targeting ability in mouse tumor models, which has been published on Eur J Cancer. In addition, study results have demonstrated that endoglin is overexpressed and up-regulated in tumor-associated angiogenic vasculature. Herpes simplex virus type 1 (HSV1) is one of the most effective oncolytic virus, which can especially kill tumor cells without damaging normal cells. MIP-3α is a special chemokine of DC and we have used it to prepare in vivo DC vaccine in previous studies. In this study, we conceive a new combinatorial strategy that will reach the purpose of combination of targeting therapy, oncolytic therapy, chemotherapy, anti-angeogenesis and in vivo DC vaccine via a PEG liposome structure. In this study, we will construct a recombinant MIP-3α HSV1 (rHSV1-MIP3α) and encapsulate it in the aqueous interior of PEG liposomes which still keep aCD in nonaqueous interior (HSV1-MIP3α/aCDPL). Thereafter, we conjugate with a monoclonal antibody (mAb) against endoglin (aEND/HSV1-MIP3α/aCDPL) as a model anticancer drug. Because the anti-endolgin mAb on the aEND/HSV1-MIP3α/aCDPL can target the endoglin expressed on the tumor endothelial cells, recombinant rHSV1-MIP3α virus cause oncolysis and express MIP-3α, and aCD directly damage tumor cells. Thus, aEND/HSV1-MIP3α/aCDPL will possess muti-functions, inducing tumor-cell lysis, immune killing of tumror cells, anti-angiogenesis and cytotoxic to tumor cells. In this study, we will apply in vitro tests such as MTT and TUNEL based immunological assays to acknowledge the capabilities of aEND/HSV1-MIP3α/aCDPL in inhibition of tumor cell proliferation and induction of tumor cell apoptosis in comparison with the control liposomes. High-performance liquid chromatography will be used to observe the biodistribution of the aEND/HSV1-MIP3α/aCDPL in tumor-bearing mice. The antitumor activities of the aEND/HSV1-MIP3α/aCDPL will be investigated in several murine tumor models. Tumor cell apoptosis and angiogenesis will be observed in tumor tissues and mice treated with aEND/HSV1-MIP3α/aCDPL by immunohistological and alginate-encapsulated tumor-cell assays. In addition, Western blto and ELISA will be used to prove whether aEND/HSV1-MIP3α/aCDPL cause cellular and humoral immunity in the treated mice. Our study will potentially provide a new combinatorial approach and facilitate the widely acceptation of aCD as cytotoxic agents for tumor therapy.