Antibody-Engineered Nanoparticles Selectively Inhibit Mesenchymal Cells Isolated from Patients with Chronic Lung Allograft Dysfunction

Abstract

Aims: Chronic lung allograft dysfunction represents the main cause of death after lung transplantation, and so far there is no effective therapy. Mesenchymal cells (MCs) are primarily responsible for fibrous obliteration of small airways typical of chronic lung allograft dysfunction. Here, we engineered gold nanoparticles containing a drug in the hydrophobic section to inhibit MCs, and exposing on the outer hydrophilic surface a monoclonal antibody targeting a MC-specific marker (half-chain gold nanoparticles with everolimus). Materials & methods: Half-chain gold nanoparticles with everolimus have been synthesized and incubated with MCs to evaluate the effect on proliferation and apoptosis. Results & discussion: Drug-loaded gold nanoparticles coated with the specific antibody were able to inhibit proliferation and induce apoptosis without stimulating an inflammatory response, as assessed by in vitro experiments. Conclusion: These findings demonstrate the effectiveness of our nanoparticles in inhibiting MCs and open new perspectives for a local treatment of chronic lung allograft dysfunction.

Original submitted 24 July 2013; Revised submitted 15 October 2013

Keywords::

• antifibrotic agent
• bronchiolitis obliterans syndrome
• chronic lung allograft dysfunction
• mesenchymal cell
• targeted drug-loaded nanoparticle

Acknowledgements

The authors thank R Allevi (Centro di microscopia elettronica per lo studio) for transmission electron microscope images, M Agozzino for immunohistochemistry advice and the facility Grandi Strumenti of the University of Pavia (Italy), particularly P Vaghi for her helpful assistance.

Financial & competing interests disclosure

M Colombo acknowledges the research fellowships of the Centro di microscopia elettronica per lo studio (University of Milan, Italy). This work was partly supported by Fondazione Regionale per la Ricerca Biomedica and NanoMeDia Project. 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

M Colombo acknowledges the research fellowships of the Centro di microscopia elettronica per lo studio (University of Milan, Italy). This work was partly supported by Fondazione Regionale per la Ricerca Biomedica and NanoMeDia Project. 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.