Sequentially Responsive Shell-Stacked Nanoparticles for Deep Penetration into Solid Tumors

Jinjin Chen, Jianxun Ding, Yucai Wang, Jianjun Cheng, Shengxiang Ji, Xiuli Zhuang, Xuesi Chen

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article number1701170
JournalAdvanced Materials
Issue number32
StatePublished - Aug 25 2017


  • cancer therapy
  • charge reversal
  • nanomedicine
  • sequential responsiveness
  • size reduction

ASJC Scopus subject areas

  • Materials Science(all)
  • Mechanics of Materials
  • Mechanical Engineering


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