Non-covalent surface integration: optimising a novel technique for preparing targeted polymeric nanoparticles for cancer therapeutics
by Anindita Mukerjee; Amalendu P. Ranjan; Jamboor K. Vishwanatha; Lawrence Helson
International Journal of Nanotechnology (IJNT), Vol. 11, No. 5/6/7/8, 2014

Abstract: Targeting anticancer drugs to their specific molecular targets is a major challenge in cancer therapy. However, advances in biomedical and protein engineering have led to novel nanoparticle targeting approaches. In this study, we used a novel non-covalent insertion of a homo-bifunctional spacer for targeted delivery of drugs to various cancer cells. Functionalised blank nanoparticles for antibody (targeting agent) conjugation were prepared using different cross-linking spacers (bis[sulphosuccinimidyl] suberate (BS3), Disuccinimidyl glutarate (DSG) and sulpho-N-[ε-maleimidocaproyloxy] sulphosuccinimide ester (s-EMCS)). The concentration of the spacers and the concentration of antibody used for conjugation were optimised using flow cytometry. The optimised and functionalised nanoparticles thus obtained were characterised for percent yield, mean particle size, surface morphology and percent antibody attachment. Our studies showed the formation of smooth and spherical functionalised poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles which could be successfully conjugated to an antibody, Anti-Annexin A2, for targeting to breast cancer cells. The functionalisation of PLGA nanoparticles for antibody attachment was effectively optimised leading to high percent attachments of 92.8% achieved with BS3. Antibody conjugated PLGA nanoparticles were then evaluated for their targeting potential. Robust intra-cellular uptake of the targeted nanoparticles was observed in breast cancer cell line and in mouse xenograft tumour studies. Our results thus validate that such a novel technique of surface integration may be used for preparing targeted polymeric nanoparticles for cancer therapeutics.

Online publication date: Tue, 16-Dec-2014

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