Intracellular microenvironment-responsive dendrimer-like mesoporous nanohybrids for traceable, effective, and safe gene delivery

Abstract

In order to create advanced functional nanocarriers for efficient gene therapy, novel intracellular microenvironment-sensitive fluorescence label-free nanostructured dendrimer-like silica hybrid nanocarriers are developed for traceable, effective, and safe gene delivery. Dendrimer-like mesoporous silica nanoparticles (DMSNs) with center-radial large pores are covalently modified with short polyethyleneimine (PEI) for efficient gene loading and binding. Autofluorescent and biodegradable PEI (AC-PEI) responsive to the intracellular microenvironment are then coated on the gene-loaded nanoparticles for inhibiting gene leakage from the carriers. Moreover, AC-PEI coating not only endows intracellular microenvironment-responsive gene release property, but also allows monitoring the gene delivery process in the absence of external labelling, owing to the pH- and GSH-responsive autofluorescence and biodegradability of AC-PEI. The resultant nanocarriers show high gene loading capacity, low cytotoxicity, stimuli-responsive gene release, label-free, and simultaneous fluorescence tracking, and high gene silencing capability. Thus, these developed nanocarriers hold substantial and promising potential as effective and safe gene-delivery carriers for future scientific investigation and practical implications in gene therapy.