Abstract
The peptide-receptor radionuclide therapy (PRRT) is a successful approach for selectively delivering radiation within tumor sites through specific recognition of radiolabeled peptides by overexpressed receptors on cancer cell surfaces. The efficacy of PRRT could be improved by using polymeric radio- and drug- therapy nanoparticles for a concomitant therapeutic effect on malignant cells. This research aimed to prepare and evaluate, a novel drug and radiation delivery nanosystem based on the 177Lu-labeled polyamidoamine (PAMAM) dendrimer (DN) loaded with paclitaxel (PTX) and functionalized on the surface with the Lys1Lys3(DOTA)-bombesin (BN) peptide for specific targeting to gastrin-releasing peptide receptors (GRPr) overexpressed on breast cancer cells. DN was first conjugated covalently to BN and DOTA (chemical moiety for lutetium-177 complexing) and subsequently loaded with PTX. The characterization by microscopic and spectroscopic techniques, in-vitro drug delivery tests as well as in in-vitro and in-vivo cellular uptake of 177Lu-DOTA-DN(PTX)-BN by T47D breast cancer cells (GRPr-positive), indicated the formation of an improved delivery nanosystem with target-specific recognition by GRPr. Results of the 177Lu-DOTA-DN(PTX)-BN effect on T47D cell viability (1.3%, compared with 10.9% of 177Lu-DOTA-DN-BN and 14.0% of DOTA-DN-(PTX)-BN) demonstrated the concomitant radiotherapeutic and chemotherapeutic properties of the polymeric nanosystem as a potential agent for the treatment of GRPr-positive tumors.
Highlights
In cases of metastatic or inoperable malignant diseases, the peptide-receptor radionuclide therapy (PRRT) is a viable option for selective delivering of radiation in tumors through specific recognition of radiolabeled peptides by receptors overexpressed on cancer cell surfaces [1].Beta emitting radionuclides, such as lutetium-177 (T1/2 = 6.7 d, βmax emission of 497 keV, γ-emission of 113 and 208 keV), are widely used in PRRT due to their relatively long-range in tissues (12 mm), which allows a cross-fire effect with the surrounding cells into the tumor.Polymers 2019, 11, 1572; doi:10.3390/polym11101572 www.mdpi.com/journal/polymersGastrin-releasing peptide receptors (GRPr) are overexpressed in breast, prostate, gastric, colon, and pancreatic tumors [2]
Lys1 Lys3 (DOTA)-bombesin (BN) peptide for specific targeting to gastrin-releasing peptide receptors (GRPr) overexpressed on breast cancer cells
Discussion have extensively been reported as drug delivery systems for carrying therapeutic and diagnostic agents, but their capacity for concomitant applications of chemotherapy dendrimers have(177 extensively been reportedmultifunctional as drug delivery systemshas for not carrying (Paclitaxel)
Summary
In cases of metastatic or inoperable malignant diseases, the peptide-receptor radionuclide therapy (PRRT) is a viable option for selective delivering of radiation in tumors through specific recognition of radiolabeled peptides by receptors overexpressed on cancer cell surfaces [1]. Beta emitting radionuclides, such as lutetium-177 (T1/2 = 6.7 d, βmax emission of 497 keV, γ-emission of 113 and 208 keV), are widely used in PRRT due to their relatively long-range in tissues (12 mm), which allows a cross-fire effect with the surrounding cells into the tumor. The nanoparticles designed as drug delivery systems can improve the bioavailability and selective accumulation of drugs at the pathological site, overcoming the challenges faced by potent anticancer medicines related to the systemic side effects and multi-drug resistance [6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
