Histone H2A-peptide-hybrided upconversion mesoporous silica nanoparticles for bortezomib/p53 delivery and apoptosis induction

Abstract

The design and development of advanced gene/drug codelivery nanocarrier with good biocompatibility for cancer gene therapy is desirable. Herein, we reported a gene delivery nanoplatform to synergized bortezomib (BTZ) for cancer treatment with histone H2A-hybrided, upconversion luminescence (UCL)-guided mesoporous silica nanoparticles [UCNPs(BTZ)@mSiO2-H2A]. The functionalization of H2A on the surface of UCNPs(BTZ)@mSiO2 nanoparticles realized the improvement of biocompatibility and enhancement of gene encapsulation and transfection efficiency. More importantly, then UCNPs(BTZ)@mSiO2-H2A/p53 induced specific and efficient apoptotic cell death in p53-null cancer cells and restored the functional activity of tumor suppressor p53 by the success of co-delivery of BTZ/p53. Moreover, the transfection with UCNPs(BTZ)@mSiO2-H2A/p53 in p53-deficient non-small cell lung cancer cells changed the status of p53 and substantially enhanced the p53-mediated sensitivity of encapsulated BTZ inside the UCNPs(BTZ)@mSiO2/p53. Meanwhile, core-shell structured mesoporous silica nanoparticles UCNPs@mSiO2 as an UCL agent can detect the real-time interaction of nanoparticles with cells and uptake/penetration processes. The results here suggested that the as-developed UCNPs(BTZ)@mSiO2-H2A/p53 nanoplatform with coordinating biocompatibility, UCL image, and sustained release manner might be desirable gene/drug codelivery nanocarrier for clinical cancer therapy.