Hydrophobicity-Adaptive Nanogels for Programmed Anticancer Drug Delivery

Hao Yang, Qin Wang, Zifu Li, Fuying Li, Di Wu, Man Fan, Anbi Zheng, Bo Huang, Lu Gan, Yuliang Zhao, Xiangliang Yang

Research output: Contribution to journalArticlepeer-review

73 Scopus citations


Reconciling the conflicting needs for a prolonged circulation time, enhanced cellular uptake by bulk tumor cells and cancer stem cells (CSCs), and extensive tumor tissue penetration remains a major challenge for current nano drug delivery systems. Here we describe smart poly(N-isopropylacrylamide)-based nanogels with a fast adaptive hydrophobicity to solve these contradictory requirements for enhanced cancer chemotherapy. The nanogels are hydrophilic in the blood to prolong their circulation time. Once they accumulate at tumor sites, they rapidly become hydrophobic in response to tumor extracellular acidity. The adaptive hydrophobicity of the nanogels facilitates tumor accumulation, deep tumor penetration, and efficient uptake by bulk tumor cells and CSCs, resulting in a greater in vivo enrichment in tumor cells and side population cells. Together with lysosomal pH-regulated charge reversal and redox-responsive intracellular drug release, the nanogels escape from lysosomes and release their cargo doxorubicin. Thus, the nanogels significantly improve the in vivo anticancer efficacy and decrease side effects of doxorubicin. Strikingly, the ratio of CSCs is greatly decreased after treatment with the nanogels loaded with doxorubicin. Our current study provides new insights into designing effective anticancer drug delivery systems.

Original languageEnglish (US)
Pages (from-to)7909-7918
Number of pages10
JournalNano Letters
Issue number12
StatePublished - Dec 12 2018


  • Hydrophobicity-adaptive nanogels
  • cancer chemotherapy
  • pH-responsiveness
  • tumor penetration

ASJC Scopus subject areas

  • Bioengineering
  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics
  • Mechanical Engineering


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