Preparation, characterization and evaluation of two controlled release therapeutic radiopharmaceuticals based on polymeric nano systems

Currently, cancer is one of the main causes of mortality on a global scale. The urgent need for the availability of systems, which would allow successful therapy, has encouraged the development of multifunctional nano systems that combine pharmacological therapeutic alternatives aimed at specific sites and tracking strategies to monitor the evolution of the pathology. Polymeric nano structures have been widely described as drug carrier systems that, through active targeting, favor the delivery of antineoplastic therapies to the tumor site and not healthy tissues. Additionally, the administration of gamma-emitting radionuclides, allow the monitoring of the disease in time and space, through the acquisition of molecular images in real time. Recently, polymeric nano structures conjugated to chelating agents as means for anchoring radionuclides which possess theranostics (therapy and diagnosis) capabilities, have been proposed. Nanoparticles based on poly (lactic-co-glycolic acid) (PLGA) and dendrimers based on poly (amidoamine) (PAMAM) have been widely used due to their biocompatibility characteristics, in combination with Paclitaxel, in order to produce an enhanced therapeutic effect; currently, research concerning the effect of combined chemotherapy/radiotherapy modalities, is limited. Therefore, in the present work, the use of the ¹⁷⁷Lu radionuclide is proposed, using 1,4,7,10-tetraaza cyclododecane-N , N ', N' ', N' '' – tetraacetic acid (DOTA) as a chelator and bombesin as a targeting linker to the gastrin-releasing peptide, so that, conjugated to the polymeric structures of PLGA or PAMAM and loaded with Paclitaxel, an effective and specific therapy for cancers positive for gastrin-releasing peptide receptors is obtained. (author)