Assessment of Tumor Antigen-Loaded Solid Lipid Nanoparticles as An Efficient Delivery System for Dendritic Cell Engineering

Abstract

Aim: The work attempts to overcome tumor-associated immune tolerance using a surface-modified solid lipid nanoparticle (SLNP) delivery system for dendritic cell (DC) immunotherapy. Materials & methods: Different formulations of SLNPs (SLNPs-alone, cationic SLNPs and mannosylated SLNPs) were prepared using tumor cell lysates. Prepared nanoparticles were characterized and their ability to activate DCs to induce a tumor cell-specific response was assessed. Results: SLNPs induced a strong phagocytic signal to DCs without any significant toxicity. Comparatively, mannosylated SLNPs evoked an optimum and effective cell-mediated immune response with no significant toxicity. Conclusion: Surface-modified SLNPs may play a pivotal role in designing a clinically translatable DC-based immunotherapy for gastrointestinal malignancies. This novel approach may also facilitate the treatment of residual disease, following standard therapy.

Original submitted 9 February 2012; Revised submitted 19 August 2012; Published online 14 January 2013

Keywords::

• cancer immunotherapy
• gastrointestinal cancer
• immune tolerance
• nanomedicine
• translational oncology

Author contributions

PK Mishra conceived and designed the studies; A Bhargava performed the majority of experiments; D Mishra prepared and characterized the nanoparticles; and S Khan assisted in flow-cytometric analysis. SK Varshney and S Banerjee helped in sample collection and data analysis; and PK Mishra and A Bhargava wrote the paper.

Financial & competing interests disclosure

The investigations were partly supported by the Council of Scientific and Industrial Research and the Department of Biotechnology, Government of India (New Delhi, India). 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

The investigations were partly supported by the Council of Scientific and Industrial Research and the Department of Biotechnology, Government of India (New Delhi, India). 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.