Quaternary Ammonium Palmitoyl Glycol Chitosan (GCPQ) Loaded with Platinum-Based Anticancer Agents—A Novel Polymer Formulation for Anticancer Therapy

Author(s)

Yvonne Lerchbammer-Kreith, Michaela Hejl, Nadine S. Sommerfeld, Xian Weng-Jiang, Uchechukwu Odunze, Ryan D. Mellor, David G. Workman, Michael A. Jakupec, Andreas G. Schätzlein, Ijeoma F. Uchegbu, Mathea S. Galanski, Bernhard K. Keppler

Abstract

Quaternary ammonium palmitoyl glycol chitosan (GCPQ) has already shown beneficial drug delivery properties and has been studied as a carrier for anticancer agents. Consequently, we synthesised cytotoxic platinum(IV) conjugates of cisplatin, carboplatin and oxaliplatin by coupling via amide bonds to five GCPQ polymers differing in their degree of palmitoylation and quaternisation. The conjugates were characterised by ¹H and ¹⁹⁵Pt NMR spectroscopy as well as inductively coupled plasma mass spectrometry (ICP-MS), the latter to determine the amount of platinum(IV) units per GCPQ polymer. Cytotoxicity was evaluated by the MTT assay in three human cancer cell lines (A549, non-small-cell lung carcinoma; CH1/PA-1, ovarian teratocarcinoma; SW480, colon adenocarcinoma). All conjugates displayed a high increase in their cytotoxic activity by factors of up to 286 times compared to their corresponding platinum(IV) complexes and mostly outperformed the respective platinum(II) counterparts by factors of up to 20 times, also taking into account the respective loading of platinum(IV) units per GCPQ polymer. Finally, a biodistribution experiment was performed with an oxaliplatin-based GCPQ conjugate in non-tumour-bearing BALB/c mice revealing an increased accumulation in lung tissue. These findings open promising opportunities for further tumouricidal activity studies especially focusing on lung tissue.

Organisation(s)

Department of Inorganic Chemistry, NMR Centre

External organisation(s)

University College London, Research Cluster Translational Cancer Therapy Research

Journal

Pharmaceuticals

Volume

16

DOI

https://doi.org/10.3390/ph16071027

Publication date

07-2023

Peer reviewed

Yes

Austrian Fields of Science 2012

301207 Pharmaceutical chemistry, 301904 Cancer research

Keywords

ASJC Scopus subject areas

Molecular Medicine, Pharmaceutical Science, Drug Discovery

Sustainable Development Goals

SDG 3 - Good Health and Well-being

Portal url

https://ucrisportal.univie.ac.at/en/publications/f68bcbe9-0d8e-497b-82cf-83a1e30c0bc8