PH-induced transformation of biodegradable multilamellar nanovectors for enhanced tumor penetration

Shoupeng Cao, Loai K.E.A. Abdelmohsen, Jingxin Shao, Joep van den Dikkenberg, Enrico Mastrobattista, David S. Williams, Jan C.M. van Hest

Research output: Contribution to journalArticleAcademicpeer-review

16 Citations (Scopus)
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Abstract

Herein we describe biodegradable nanovectors comprised of block copolymers of poly(ethylene glycol) and poly(trimethylene carbonate) (PEG-PTMC) that change their morphology and surface charge when exposed to tumor environment conditions. Well-defined, drug-loaded nanovectors were prepared via direct hydration using liquid oligo(ethylene glycol) as a dispersant. Systematic introduction of basic imidazole-functional TMC derivatives, through modular polymerization, resulted in polymers that self-assembled in multilamellar nanoparticles (at neutral pH) and that were loaded with hydrophobic drugs. The resultant multilamellar nanovectors demonstrated a significant size reduction and charge reversal at pH ≈ 6.5, which yielded cationic nanovectors that were tailored for tumor penetration. In vitro studies using 3D heterospheroids demonstrate that this platform has excellent potential to promote enhanced tumor penetration under physiological conditions.

Original languageEnglish
Pages (from-to)1394-1399
Number of pages6
JournalACS Macro Letters
Volume7
Issue number11
DOIs
Publication statusPublished - 20 Nov 2018

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