The invention belongs to the field of pharmaceutic preparations, and relates to a targeted ligand-PEG (
polyethylene glycol)-
cholesterol /
tocopherol derivative, and a preparation method and an application of the derivative, in particular to an application of the derivative in a composite mechanism mediate
tumor targeted drug delivery system. According to the derivative, the preparation method and the application, a
drug delivery system consisting of the targeted ligand-PEG-
cholesterol /
tocopherol derivative with a targeting function, a
long circulating function and a pH (power of
hydrogen) sensitive function as a functional material, a cation
liposome and a
drug can simultaneously carry anticancer polypeptide and
gene /
chemotherapy drugs. According to the
system, different drugs are jointly entrapped into the lipid
nano drug delivery system and delivered into a targeted
cell by utilizing a physicochemical property difference between components or by in-vivo specific targeted recognition,
signal conduction blocking and pH triggering PEG chain breaking charge reversion methods, so that a targeted tumor
therapeutic effect is improved. According to the derivative, the preparation method and the application, the advantages of the
system in directional delivery, co-delivery and the like are proved by in-vivo and in-vitro activity evaluation, the anticancer activity is improved significantly, and definite synergic therapeutic and
immunity effects are provided.