A new paper by Wang et al. reports the facile synthesis of dispersed polyacrylic acid (PAA)/calcium carbonate nanoparticles which show ultrahigh loading capacity for the liver cancer drug doxorubin (DOX), in addition to its pH sensitive release.
While calcium carbonate particles are attractive potential drug delivery vehicles due to their biocompatibility and pH sensitivity, previously synthesised particles have been micrometer sized and show only limited drug uptake, both of which present barriers to their use. These issues have now been overcome. Using PAA-sodium salt as a template, PAA/calcium carbonate particles were produced with an average size of 120 nm by ion exchange followed by heating in carbon dioxide (see diagram below).
The presence of carboxylate groups in PAA is the root of the new nanoparticles’ high uptake of positively charged molecules such as DOX– up to 98 % loading efficiency was observed. Release of DOX was shown to be faster in mildly acidic conditions like that in extracellular cancer cells, allowing targeting of these cells.
The anti-cancer activity of DOX-loaded PAA/calcium carbonate particles in vitro was compared to DOX-free particles and free DOX using the standard MTT assay. Cytotoxicity of free DOX was similar to that of the DOX-loaded particles, while the DOX-free particles showed no cytotoxicity. The performance of free-DOX was also compared to DOX-loaded nanoparticles in vivo. Compared to the control, the group treated with DOX-loaded nanoparticles showed a 76 % reduction in liver tumour size, while the group treated with free DOX showed a 41 % reduction. In addition, there were no toxic effects observed for DOX-loaded particles.
These results demonstrate the potential application of PAA/calcium carbonate nanoparticles as delivery vehicles for doxorubin. Further studies are being carried out to investigate the inclusion of magnetic and/or fluorescent compounds to produce multifunctional materials for simultaneous cancer diagnostic and therapeutic application.
For more information, see the full paper at:
Designed preparation of polyacrylic acid/calcium carbonate nanoparticles with high doxorubicin payload for liver cancer chemotherapy
Hanzhu Shi, Lu Li, Lingyu Zhang, Tingting Wang, Chungang Wang, Dongxia Zhu and Zhongmin Su
CrystEngComm, 2015, Advance Article
DOI: 10.1039/C5CE00708A
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Gwenda Kyd has a PhD in metallocarborane chemistry from the University of Edinburgh. Other research work includes the spectroscopic study of the structure of glasses and organometallic electron-transfer reactions and the preparation of new inorganic phosphors. She has recently published a book on chemicals from plants.
