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Direct Nucleus‐Targeted Drug Delivery Using Cascade pH e /Photo Dual‐Sensitive Polymeric Nanocarrier for Cancer Therapy
Author(s) -
Cao Ziyang,
Li Dongdong,
Wang Junxia,
Xiong Menghua,
Yang Xianzhu
Publication year - 2019
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.201902022
Subject(s) - nanocarriers , drug delivery , nanotechnology , cancer therapy , dual (grammatical number) , anticancer drug , materials science , drug , chemistry , cancer , pharmacology , medicine , art , literature
The 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 (pH e )‐sensitive transactivator of transcription (TAT) peptide (DA‐masked TAT‐decorating reactive oxygen species (ROS)‐sensitive Ce6/DOX‐loaded hyperbranched nanoparticles ( D TRCD)) are explored for cascade nucleus‐targeted drug delivery. Following administration, D TRCD 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 reactivating the TAT targeting capability in tumor tissue. Subsequently, ROS generated by D TRCD under 660 nm laser not only disrupts the nuclear membrane to allow entry into the nuclei but also triggers intracellular release of the payload in the nuclei. As evidenced by in vivo experiments, such pH e /photo dual‐sensitive polymeric nanocarriers offer remarkable therapeutic effects, efficiently suppressing tumor growth. This multistage cascade nucleus‐targeted drug delivery concept provides new avenues to develop nucleus‐targeted drug delivery systems.