Direct Nucleus ‐Targeted Drug Delivery Using Cascade pHe/Photo Dual‐Sensitive Polymeric Nanocarrier for Cancer Therapy

Cascade pHe/photo dual ‐sensitive 2,3‐dimethylmaleic anhydride‐masked transactivator of transcription (TAT)‐decorating reactive oxygen species (ROS)‐sensitive Ce6/doxorubicin‐loaded hyperbranched nanoparticles (DTRCD) are explored for direct nucleus ‐targeted drug delivery. The TAT targeting effect ofDTRCD is masked to prolonged circulation and reactivated at tumor tissue to enhance cell uptake and translocation into the perinuclear region. Subsequently,DTRCD generates ROS under illumination to disrupt the nuclear membrane to allow nanoparticle entry and trigger intranuclear drug release. AbstractThe cell nucleus ‐targeted delivery of therapeutic agents plays a critical role in cancer therapy, since the biological target of many anticancer therapeutics is the cell nucleus. However, multiple physiological barriers limit the delivery efficiency of free drugs, resulting in unsatisfactory therapeutic effects. Herein, thioketal crosslinked polyphosphoester‐based nanoparticles with a tumor acidity (pHe) ‐sensitive transactivator of transcription (TAT) peptide (DA‐masked TAT‐decorating reactive oxygen species (ROS)‐sensitive Ce6/DOX‐loaded hyperbranched nanoparticles (DTRCD)) are explored for cascade nucleus ‐targeted drug delivery. Following administration,DTRCD experiences prolonged circulation by masking the targeting effect of its TAT peptide and then achieves enhanced tumor cell uptake and improved translocation into the perinuclear region by react...

Source: Small - July 17, 2019 Category: Nanotechnology Authors: Ziyang Cao, Dongdong Li, Junxia Wang, Menghua Xiong, Xianzhu Yang Tags: Full Paper Source Type: research