Exploiting nanoscale cooperativity for precision medicine

Jonathan Wilhelm, Zhaohui Wang, Baran D. Sumer, Jinming Gao

Research output: Contribution to journalReview articlepeer-review

15 Scopus citations


Precise spatiotemporal control of molecular transport is vital to functional physiological systems. Nature evolved to apply macromolecular cooperativity to achieve precision over systemic delivery of important molecules. In drug delivery, conventional nanocarriers employ inert materials and rely on passive accumulation for tissue targeting and diffusion for drug release. Early clinical studies show these nanodrugs have not delivered the anticipated impact on therapy. Inspired by nature, we propose a design principle that incorporates nanoscale cooperativity and phase transition to sense and amplify physiological signals to improve the therapeutic outcome. Using ultra-pH-sensitive (UPS) nanoparticles as an example, we demonstrate how all-or-nothing protonation cooperativity during micelle assembly/disassembly can be exploited to increase dose accumulation and achieve rapid drug release in acidic microenvironments. In a separate study, we show the effectiveness of a single polymer composition to accomplish cytosolic delivery of tumor antigens with activation of stimulator of interferon genes (STING) in lymph node-resident dendritic cells for cancer immunotherapy. Molecular cooperativity is a hallmark of nanobiology that offers a valuable strategy to functionalize nanomedicine systems to achieve precision medicine.

Original languageEnglish (US)
Pages (from-to)63-72
Number of pages10
JournalAdvanced Drug Delivery Reviews
StatePublished - Jan 2020


  • All-or-nothing protonation
  • Cancer immunotherapy
  • Phase transition
  • Tumor-targeted drug delivery
  • Ultra-pH sensitive micelles
  • pH-activatable drug release

ASJC Scopus subject areas

  • Pharmaceutical Science


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