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Sequentially Responsive Shell‐Stacked Nanoparticles for Deep Penetration into Solid Tumors
Author(s) -
Chen Jinjin,
Ding Jianxun,
Wang Yucai,
Cheng Jianjun,
Ji Shengxiang,
Zhuang Xiuli,
Chen Xuesi
Publication year - 2017
Publication title -
advanced materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 10.707
H-Index - 527
eISSN - 1521-4095
pISSN - 0935-9648
DOI - 10.1002/adma.201701170
Subject(s) - nanomedicine , penetration (warfare) , materials science , nanoparticle , nanotechnology , doxorubicin , biophysics , surface charge , penetration depth , disulfide bond , particle size , drug delivery , biomedical engineering , chemical engineering , chemistry , chemotherapy , medicine , biochemistry , surgery , biology , optics , physics , operations research , engineering
Nanomedicine to overcome both systemic and tumor tissue barriers ideally should have a transformable size and surface, maintaining a certain size and negative surface charge for prolonged circulation, while reducing to a smaller size and switching to a positive surface charge for efficient penetration to and retention in the interstitial space throughout the tumor tissue. However, the design of such size and charge dual‐transformable nanomedicine is rarely reported. Here, the design of a shell‐stacked nanoparticle (SNP) is reported, which can undergo remarkable size reduction from about 145 to 40 nm, and surface charge reversal from −7.4 to 8.2 mV at acidic tumor tissue, for enhanced tumor penetration and uptake by cells in deep tumor tissue. The disulfide‐cross‐linked core maintains the stability of the particle and prevents undesired premature drug release until the shedding of the shell, which accelerates the cleavage of more exposed disulfide bond sand intracellular drug release. SNP penetrates about 1 mm into xenografted A549 lung carcinoma, which is about four times penetration depth of the nontransformable one. The doxorubicin (DOX)‐loaded SNP (SNP/DOX) shows significant antitumor efficacy and nearly eradicates the tumor, substantiating the importance of the design of size and charge dual‐transformable nanomedicine.