As such, the lipid bilayer prevented gemcitabine leakage, si-HIF1α degradation, and nanoparticle aggregation in serum. An equally important finding is that the hybrid structure of CSHNs ensured the prolonged lifespan of entrapped Gemcitabine in the bloodstream and enhanced the release of the drug in tumour tissues by enhancing the effect of tumour vasculature. As a result, CSHNs could effectively suppress HIF1α expression both in vitro and in vivo, and the therapeutic agents exhibited synergistic antitumor effects in the orthotopic tumour model .