G. Mann, A. Kaul, M. Thirumal, A.K. Mishra, A. Datta
University of Delhi,
Keywords: mesoporous silica nanoparticles, ER+ breast cancer, theranostics, SPECT, estrogen receptor
Summary:Synthesis of Target Responsive Nanoparticles with Theranostic Properties Garima Mann1,2, Ankur Kaul1, M. Thirumal2, A.K. Mishra1, Anupama Datta1* 1Institute of Nuclear Medicine and Allied Sciences, DRDO, Delhi, 110054, India 2Department of Chemistry, University of Delhi, Delhi, 110007 *email@example.com, firstname.lastname@example.org INTRODUCTION: About 80% of all breast cancers are “ER-positive”. These are estrogen receptor specific with Tamoxifen, a selective estrogen receptor modulator (SERM), as the recommended mode of therapy. Combining these properties with diagnostic imaging modality such as SPECT provides a useful and effective theranostic approach for curating cancer therapy. To amalgamate target specificity with therapy and diagnostics, mesoporous silica nanoparticles were utilized as nanocarriers. Mesoporous silica nanoparticles display excellent in vivo stability, large surface area and ease of surface functionalization. These properties make them ideal for targeted drug delivery; the drugs are encapsulated in the pores while the surface can be modified to make the nanoparticles target specific. AIM: The work being presented here focusses on developing functionalized mesoporous silica nanoparticles with ER+ breast cancer as the target. The pores were utilized for drug encapsulation while the surface was dually functionalized to make the nanoparticles target specific as well as attach a SPECT imaging probe. MATERIALS AND METHODS: Synthesis followed the modified Stober synthesis process with co-condensation of azido silane to give azide functionalized MCM-41 mesoporous silica nanoparticles which were further functionalized with amine. The estrogen target was attached by a facile and clean ‘click’ chemistry synthesis. The surface amine groups were further modified to attach DTPA chelator to bind the 99mTc radioactive ion for scintigraphy purposes. The pores were loaded with Tamoxifen molecule and capped to avoid drug leeching. RESULT AND CONCLUSIONS: Dual functionalised spherical mesoporous silica nanoparticles were successfully synthesised, and all the steps were characterised using IR and TGA analysis. The surface of MSNs was functionalised with chelator DTPA and targeting estrogen receptor by ‘click chemistry’. Acetylated dextran molecule served as pore capping agent after conjugation to azide functional group present on silica surface. SEM and TEM confirmed the spherical morphology and ̴120nm particle size while pore size of 4nm was confirmed using BET. Radiolabelling studies with 99mTc and drug loading capacity studies are underway. Further in vitro and in vivo studies on tumour bearing mice will be carried out to establish the efficacy of these nanoparticles for targeting ER+ breast cancer.