"Clickable" polymer-caged nanobins as a modular drug delivery platform

Sang Min Lee, Haimei Chen, Thomas V. O'Halloran, Son Binh T. Nguyen

Research output: Contribution to journalArticlepeer-review

83 Scopus citations

Abstract

Modularly clickable polymer-caged nanobins (PCNs) were prepared from liposome templates using a drop-in cholesterol-modified poly(acrylic acid) reagent followed by cross-linking with alkynefunctionalized diamine linker that allows for the conjugation of azide-modified targeting ligands via click ligation. These PCNs possess pH-responsive characteristics that can be used to trigger the release of encapsulated doxorubicin (DXR) payload inside the liposomal core under mild acidic conditions. After click-conjugation with azide-modified folate as an active targeting ligand, the resulting folate-conjugated, DXR-loaded PCNs (f-PCNDXR) demonstrated enhanced potency to folate receptor (FR)-positive tumor cells such as KB and OvCa432 over FR-negative MCF7 cells. f-PCNDXR can readily discriminate FR-positive tumor cells as a function of the level of cellular FR-expression, showing different degrees of potentiation in each cell. With both targeting functionalities and pH-sensitive drug-releasing triggers, f-PCNDXR was fifty-times more potent than the untargeted agent toward cancer cells that overexpress the folate target receptors.

Original languageEnglish (US)
Pages (from-to)9311-9320
Number of pages10
JournalJournal of the American Chemical Society
Volume131
Issue number26
DOIs
StatePublished - Jul 8 2009

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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