The study is aimed
to develop a versatile reticular polyethylenimine
(PEI) derivative eprosartan-g-PEI (ESP) conjugate-mediated
targeted drug and gene codelivery system for tumor therapy. Eprosartan
(ES), an angiotensin II type 1 receptor blocker (ARB), which has been
proven to exert beneficial effects on tumor progression, vascularization,
and metastasis as the conventional antihypertensive drug, was conjugated
with PEI-1.8K chains into ESP via a bis-amide bond of pH-sensitivity
to overcome high cytotoxicity and nontargeted gene delivery of PEI-25K.
P53 gene was encapsulated in the ESP to form the codelivery system
of ESP/p53 complexes, and this system was comprehensively characterized. In vitro ESP/p53 complexes had a significant effect on inhibiting
angiogenesis by reducing the expression and secretion of VEGF. In vivo the effective antitumor activity of ESP/p53 complexes
was observed on nude mice bearing PANC-1 xenografts, and the microvessel
density (MVD) examination demonstrated that ESP/p53 complex-produced
antitumor efficacy was closely correlated with the efficient angiogenesis
repression. These findings disclosed that the multifunctional ESP/p53
complexes might be a promising dual anticancer drug and gene codelivery
system.