Small molecule inhibitors against protein geranylgeranyltransferase-I such as P61A6 have been shown to inhibit proliferation of a variety of @entity1 @entity5 cells and exhibit antitumor activity in @entity19 models. Development of these inhibitors could be dramatically accelerated by conferring @entity5 targeting and controlled release capability. As a first step towards this goal, we have encapsulated P61A6 into a new type of liposomes that open and release cargos only under low pH condition. These low pH-release type liposomes were prepared by adjusting the ratio of two types of phospholipid derivatives. Loading of @entity68882 ( @entity68882 ) generated liposomes with average diameter of 50-100 nm. @entity68882 release in solution was sharply dependent on pH values, only showing release at pH lower than 6. Release of cargos in a pH-dependent manner inside the cell was demonstrated by the use of a proton pump inhibitor @entity7999 that Increased lysosomal pH and inhibited the release of a dye carried in the pH-liposome. Delivery of @entity68882 to @entity1 @entity788 cells was demonstrated by the inhibition of protein geranylgeranylation inside the cell and this effect was blocked by @entity7999 . In addition, @entity68882 delivered by pH-liposomes induced proliferation inhibition, G1 cell cycle arrest that is associated with the expression of cell cycle regulator @entity994 / @entity994 . Proliferation inhibition was also observed with @entity2 cell lines. Availability of nanoformulated @entity68882 opens up the possibility to combine with other types of inhibitors. To demonstrate this point, we combined the liposomal- @entity68882 with farnesyltransferase inhibitor (FTI) to inhibit @entity984 signaling in @entity788 cells. Our results show that the activated @entity984 signaling in these cells can be effectively inhibited and that synergistic effect of the two drugs is observed. Our results suggest a new direction in the use of @entity68882 for @entity5 therapy.

Nanoformulation of Geranylgeranyltransferase-I Inhibitors for XXXX Therapy: Liposomal Encapsulation and pH-Dependent @entity5 Cells.

@entity1 :: ('9606', 'Species') :: ['human'] @entity994 :: ('1026', 'Gene') :: ['p21CIP1', 'WAF1'] @entity788 :: ('MESH:D010190', 'Disease') :: ['pancreatic cancer'] @entity19 :: ('10090', 'Species') :: ['mouse'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'cancer'] @entity984 :: ('3845', 'Gene') :: ['K-Ras'] @entity2 :: ('MESH:D008175', 'Disease') :: ['various lung cancer'] @entity68882 :: ('5229', 'Gene') :: ['GGTI', 'geranylgeranyltransferase-I inhibitor'] @entity7999 :: ('MESH:C040929', 'Chemical') :: ['Bafilomycin A1']
@entity5 :: (MESH:D009369,Disease) :: ['Cancer']
