Suppression of ovarian cancer growth via systemic administration with liposome-encapsulated adenovirus-encoding endostatin

Abstract

Gene therapy using adenoviral vector containing the endostatin gene is a promising strategy for advanced cancers. However, host immune response to adenovirus and the lack of the requisite coxsackie-adenovirus receptor (CAR) in many primary cells limit the in vivo application. Liposome-complexed adenoviral vectors have proven to be useful for enhancing gene delivery in target cells that lack adenoviral receptors and avoiding a neutralizing antibody response. Here, we investigated antitumor effects of intravenous administration with PEG-PE cationic liposome-encapsulated recombinant human endostatin adenovirus (Ad-hEndo) on CAR-negative ovarian cancer. Electron micrography (EM) showed that these liposomes efficiently encapsulated the vectors, allowing CAR-independent adenovector transduction. The results showed that the complex enhanced transfection efficiency of recombinant adenovirus. Prolonged systemic administration was performed in immunocompetent mice and did not induce significant antibody response. The antitumor effect with PEG-PE cationic liposome encapsulated with Ad-hE (Ad-hE/lipo) was evaluated in the human ovarian cancer model. Systemic administration was well tolerated and resulted in marked suppression of tumor growth in an established ovarian cancer model, which was associated with a decreased number of micro-vessels and increased apoptosis of tumor cells. Our study shows that PEG-PE cationic liposome-encapsulated Ad-hE (Ad-hE/Lipo) can be administrated intravenously and lastingly to inhibit angiogenesis, thus showing promising clinical application.

Systemically administered liposome-encapsulated Ad-PEDF potentiates the anti-cancer effects in mouse lung metastasis melanoma

“…Neutralizing antibodies of Ad vector was prepared as before [31]. After obtained the neutralizing antibodies, complexes of Ad-GFP and DOTAP and cholesterol cationic liposomes were used to infect B16-F10 melanoma cells with or without the serum containing the neutralizing antibody at 37°C for 4 h. Then, cells were washed with phosphate-buffered saline to remove the complexes.…”

Comparison of two kinds of nanomedicine for targeted gene therapy: premodified or postmodified gene delivery systems

“…32 A series of PEG-PE conjugates has been used for the modification of various vehicles to create active targeting nanocarriers capable of spontaneous accumulation at specific sites. [33][34][35][36] In this research, novel conjugated mannan-containing PEG-PE ligands were synthesized and MN-PEG-PEmodified SLN were investigated. Here, mannan is the target moiety which can bind to the mannose receptor in the macrophage, and PEG-PE is the spacer linked onto the surface of the SLN.…”

Update on oncolytic viral therapy – targeting angiogenesis

“…The endostatin gene has been engineered to be expressed by oncolytic adenovirus, adeno-associated virus and HSV,86–93 showing better efficacy than control or nonreplicating viruses expressing endostatin.…”