Distribution and Clearance of PEG-Single-Walled Carbon Nanotube Cancer Drug Delivery Vehicles in Mice

Abstract

Aims: To study the distribution and clearance of polyethylene glycol (PEG)-ylated single-walled carbon nanotube (SWCNTs) as drug delivery vehicles for the anticancer drug cisplatin in mice. Materials & methods: PEG layers were attached to SWCNTs and dispersed in aqueous media and characterized using dynamic light scattering, scanning transmission electron microscopy and Raman spectroscopy. Cytotoxicity was assessed in vitro using Annexin-V assay, and the distribution and clearance pathways in mice were studied by histological staining and Raman spectroscopy. Efficacy of PEG-SWCNT–cisplatin for tumor growth inhibition was studied in mice. Results & discussion: PEG-SWCNTs were efficiently dispersed in aqueous media compared with controls, and did not induce apoptosis in vitro. Hematoxylin and eosin staining, and Raman bands for SWCNTs in tissues from several vital organs from mice injected intravenously with nanotube bioconjugates revealed that control SWCNTs were lodged in lung tissue as large aggregates compared with the PEG-SWCNTs, which showed little or no accumulation. Characteristic SWCNT Raman bands in feces revealed the presence of bilary or renal excretion routes. Attachment of cisplatin on bioconjugates was visualized with Z-contrast scanning transmission electron microscopy. PEG-SWCNT–cisplatin with the attached targeting ligand EGF successfully inhibited growth of head and neck tumor xenografts in mice. Conclusions: PEG-SWCNTs, as opposed to control SWCNTs, form more highly dispersed delivery vehicles that, when loaded with both cisplatin and EGF, inhibit growth of squamous cell tumors.

Keywords::

• biodistribution
• cancer
• carbon nanotube
• cisplatin
• clearance
• drug delivery
• dynamic light scattering
• growth factor
• H & E staining
• polyethylene glycol
• Raman spectroscopy
• STEM

Financial & competing interests disclosure

This research was supported by the Intramural Programs of the National Institute of Dental and Craniofacial Research and the National Institute of Biomedical Imaging and Bioengineering, NIH, and in part by PHS grant ES013557 from NIEHS/NIH to JFR, University of Connecticut. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This research was supported by the Intramural Programs of the National Institute of Dental and Craniofacial Research and the National Institute of Biomedical Imaging and Bioengineering, NIH, and in part by PHS grant ES013557 from NIEHS/NIH to JFR, University of Connecticut. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.