RADIOLABELED NANOPARTICLES STRATEGIES FOR BREAST CANCER THERAGNOSIS

Introduction Nanomedicine offers an exciting new paradigm change for real medicine, which can be translated into a huge impact on health care. This is mainly due to the possibility of combination treatment strategies and... [ view full abstract ]

Introduction
Nanomedicine offers an exciting new paradigm change for real medicine, which can be translated into a huge impact on health care. This is mainly due to the possibility of combination treatment strategies and diagnostic techniques, known as theragnosis.
Objective
The objective of present work is to develop double functionalized PLGA nanoparticles for breast cancer theragnosis. PLGA nanoparticles were radiolabeled with 99mTc and particle surface were modified with a monoclonal antibody (MAb) against HER2+ cancer cells.
Materials and Methods
PLGA nanoparticles were prepared by nanoprecipitation method [1]. Loaded nanoparticles were prepared dissolving paclitaxel (a gift from PhytoBiotech, Canada) into polymer solution in acetone at 10 % w/w concentration.
Different radiolabeling strategies were carried out [2]:
(i) PLGA nanoparticles were surface modified with a MAb against HER2 + cancer cells using the carbodiimide strategy. Then, nanoparticles were radiolabeled with 99mTc directly using SnCl2.
(ii) Antibody was firstly reduced using a ß-mercaptoethanol. For this purpose, MAb was incubated for 30 min at room temperature. After purification (Amicon 30K) to eliminate the excess of ß-mercaptoethanol, the reduced antibody was labeled with 99mTc (10 mCi) via Sn2+ reduction of pertechnetate, using sodium pirophospate (Angiocis® 20mg) as a weak competing ligand.
MAb Conjugation Efficiency was evaluated by Bradford method.
Results and Discussion
We obtained paclitaxel-loaded PLGA nanoparticles 190 nm in diameter with a zeta potential around -20 mV. Encapsulation efficiency was 85% (determined by HPLC). After antibody conjugation particles diameter increases slightly up to 250 nm in diameter. ZP values were nearly neutrality which indicates the presence of MAb on particle surface. Antibody conjugation efficiency was around 90%. That means 30-35 g of MAb per gof nanoparticle.
Both radiolabeling strategies were highly effective (up to 98%).

References
[1] Fessi, H., Puisieux, F., Devissaguet, J.P., Ammoury, N., Benita, S. Int. J. Pharm. (1989) 55, R1-R4
[2] Psimadas D, Bouziotis P, Georgoulias P, Valotassiou V, Tsotakos T, Loudos G. Contrast Media Mol Imaging. (2013), 8(4):333-339


Acknowledgements
Authors are special grateful for the financial support from Fundación Progreso y Salud (Junta de Andalucía) and Janssen Pharmaceuticals. Authors also thanks PhytoBiotech (Canada) for paclitaxel supply