The camouflage with cell membrane bestows nanoparticles with cell-like functions, such as specific recognition, long blood circulation, and immune escaping. For
cancer therapy, the nanoparticles camouflaged with
cancer cell membrane (CCM) from homologous cells show homotypic targeting delivery of small molecule compounds,
photosensitizers, or
enzymes to the
tumors. However, effective gene therapy encounters difficulties by this approach due to the properties of
nucleic acids. Herein, a
cancer cell-like gene delivery system is developed using an excellent
polymer poly(β-amino
ester) (PBAE) to condense
small interfering RNA (
siRNA) (targeting to Plk1 gene) into nanoparticles (PBAE/siPlk1) as the core, which is further camouflaged with CCM. These novel biomimetic nanoparticles CCM/PBAE/siPlk1 (CCMPP) demonstrate highly specific targeting to homotypic
cancer cells, effective downregulation of PLK1 level, and inducing apoptosis of
cancer cells. Based on the homotypic binding adhesion molecules on the CCM, the cellular internalization and homotypic-targeting accumulation to the
tumors are clearly improved. CCMPP induces highly efficient apoptosis of
cancer cells both in vitro and in vivo and results in significant
tumor inhibition. The artificial
cancer cells with homotypic properties can serve as a biomimetic delivery system for
cancer-targeted gene therapy.