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A Multifunctional Micellar Nanoplatform with pH‐Triggered Cell Penetration and Nuclear Targeting for Effective Cancer Therapy and Inhibition to Lung Metastasis
Author(s) -
Jing Yuting,
Xiong Xiang,
Ming Yang,
Zhao Jingya,
Guo Xing,
Yang Guang,
Zhou Shaobing
Publication year - 2018
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.201700974
Subject(s) - nanocarriers , internalization , endocytosis , in vivo , ethylene glycol , cytotoxicity , cancer research , chemistry , micelle , biophysics , materials science , cell , pharmacology , nanoparticle , nanotechnology , medicine , in vitro , biochemistry , biology , organic chemistry , microbiology and biotechnology , aqueous solution
The enhancement of cellular internalization and subsequent achievement of a nuclear targeting of nanocarriers play an important role in maximizing the therapeutic potency and minimizing the side effects of encapsulated drugs. Herein, a multifunctional micellar nanoplatform simultaneously with high cell penetration and nuclear targeting through pH‐triggered surface charge reversal is presented. The miscellar system is constructed from poly(ethylene glycol)‐poly(ε‐caprolactone) with 2,3‐dimethylmaleic anhydride‐Tat decoration (PECL/DA‐Tat). DA groups are used to mask the positive charge of Tat to prolong blood circulation of the nanocarriers. In the mildly acidic environment of tumor tissue, the system exhibits ultrasensitive negative to positive charge reversal, facilitating the cell internalization and subsequent nuclear targeting. The chemotherapeutic 10‐hydroxycamptothecin conjugated to methoxy polyethylene glycol, which is loaded in this micelle, obviously enhances cytotoxicity against tumor cells. The in vivo therapy in mice bearing 4T1 breast tumor reveals that the system has a significant enhancement of both the endocytosis and nuclear enrichment, showing a highly effective antitumor efficacy and inhibition to lung metastasis.