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Tumor‐Microenvironment‐Adaptive Nanoparticles Codeliver Paclitaxel and siRNA to Inhibit Growth and Lung Metastasis of Breast Cancer
Author(s) -
Tang Shan,
Meng Qingshuo,
Sun Huiping,
Su Jinghan,
Yin Qi,
Zhang Zhiwen,
Yu Haijun,
Chen Lingli,
Chen Yi,
Gu Wangwen,
Li Yaping
Publication year - 2016
Publication title -
advanced functional materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.069
H-Index - 322
eISSN - 1616-3028
pISSN - 1616-301X
DOI - 10.1002/adfm.201601703
Subject(s) - tumor microenvironment , cancer research , materials science , paclitaxel , drug delivery , metastasis , doxorubicin , peg ratio , cancer , medicine , nanotechnology , chemotherapy , tumor cells , finance , economics
Prolonged circulation, specific and effective uptake by tumor cells, and rapid intracellular drug release are three main factors for the drug delivery systems to win the battle against metastatic breast cancer. In this work, a tumor microenvironment‐adaptive nanoparticle co‐loading paclitaxel (PTX) and the anti‐metastasis siRNA targeting Twist is prepared. The nanoparticle consists of a pH‐sensitive core, a cationic shell, and a matrix metalloproteinase (MMP)‐cleavable polyethylene glycol (PEG) corona conjugated via a peptide linker. PEG will be cut away by MMPs at the tumor site, which endows the nanoparticle with smaller particle size and higher positive charge, leading to more efficient cellular uptake in tumor cells and higher intra‐tumor accumulation of both PTX and siRNA in the 4T1 tumor‐bearing mice models compared to the nanoparticles with irremovable PEG. In addition, acid‐triggered drug release in endo/lysosomes is achieved through the pH‐sensitive core. As a result, the MMP/pH dual‐sensitive nanoparticles significantly inhibit tumor growth and pulmonary metastasis. Therefore, this tumor‐microenvironment‐adaptive nanoparticle can be a promising codelivery vector for effective therapy of metastatic breast cancer due to simultaneously satisfying the requirements of long circulating time, efficient tumor cell targeting, and fast intracellular drug release.