Non-covalent surface integration: Optimizing a novel technique for preparing targeted polymeric nanoparticles for cancer therapeutics

Anindita Mukerjee, Amalendu Prakash Ranjan, Jamboor K. Vishwanatha, Lawrence Helson

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)676-685
Number of pages10
JournalInternational Journal of Nanotechnology
Volume11
Issue number5-8
DOIs
StatePublished - 1 Jan 2014

Fingerprint

cancer
antibodies
Antibodies
Nanoparticles
nanoparticles
spacers
attachment
Cells
conjugation
breast
drugs
Annexin A2
cytometry
Flow cytometry
blanks
cultured cells
Heterografts
Surface morphology
mice
Tumors

Keywords

  • Annexin A2
  • Breast cancer
  • Cancer therapeutics
  • Flow cytometry
  • Optimisation
  • PLGA nanoparticles
  • Targeted delivery

Cite this

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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.",
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AU - Helson, Lawrence

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