@misc{10481/85261,
year = {2023},
url = {https://hdl.handle.net/10481/85261},
abstract = {Introduction: Pancreatic cancer (PC) shows a very poor response to current treatments. Development of drug resistance is one of the
causes of the therapy failure, being PARP1 (poly ADP-ribose polymerase 1) a relevant protein in the resistance mechanism. In this
work, we have functionalized calcium phosphate-based nanoparticles (NPs) with Olaparib (OLA, a PARP-1 inhibitor) in combination
with ascorbic acid (AA), a pro-oxidative agent, to enhance their individual effects.
Methods: Amorphous Calcium Phosphate (ACP) NPs were synthesized through a biomimetic approach and then functionalized with
OLA and AA (NP-ACP-OLA-AA). After evaluation of the loading capacity and release kinetic, cytotoxicity, cell migration,
immunofluorescence, and gene expression assays were performed using pancreatic tumor cell lines. In vivo studies were carried out
on tumors derived from the PANC-1 line in NOD SCID gamma (NSG) mice.
Results: NP-ACP-OLA-AA was loaded with 13%wt of OLA (75% loading efficiency) and 1% of AA, respectively. The resulting dual
nanosystem exhibited a gradual release of OLA and AA, being the latter protected from degradation in solution. This ensured the
simultaneous availability of OLA and AA for a longer period, at least, during the entire time of in vitro cell experiments (72 hours). In
vitro studies indicated that NP-ACP-OLA-AA showed the best cytotoxic effect outperforming that of the free OLA and a higher
genotoxicity and apoptosis-mediated cytotoxic effect in human pancreatic ductal adenocarcinoma cell line. Interestingly, the in vivo
assays using immunosuppressed mice with PANC-1-induced tumors revealed that NP-ACP-OLA-AA produced a higher tumor volume
reduction (59.1%) compared to free OLA (28.3%) and increased the mice survival.
Conclusion: Calcium phosphate NPs, a highly biocompatible and biodegradable system, were an ideal vector for the OLA and AA
co-treatment in PC, inducing significant therapeutic benefits relative to free OLA, including cytotoxicity, induction of apoptosis,
inhibition of cell migration, tumor growth, and survival.},
organization = {Projects RYC2021-032734-I and PDC2022-133191-I00 (nanoSOP)},
organization = {Ministerio de Ciencia, Innovación y Universidades-Agencia Estatal de Investigación (MCIN/AEI/10.13039/ 501100011033)},
organization = {European Union NextGenerationEU/PRTR},
organization = {Project PMPTA22/00136 funded by the Instituto de Salud Carlos III (FEDER)},
organization = {University of Granada and the Spanish Ministry of Universities under the program “María Zambrano},
publisher = {Dove Medical Press LTD},
keywords = {Nanomedicine},
keywords = {Calcium phosphate nanocarriers},
keywords = {Olaparib},
keywords = {Ascorbic acid},
keywords = {Synergistic effect},
title = {Combining Olaparib and Ascorbic Acid on Nanoparticles to Enhance the Drug Toxic Effects in Pancreatic Cancer},
doi = {10.2147/IJN.S415631},
author = {Quiñonero Muñoz, Francisco José and Parra Torrejón, Belén and Ramírez Rodríguez, Gloria Belén and Garcés Robles, Víctor Jesús and Delgado López, José Manuel and Jiménez Luna, Cristina and Perazzoli, Gloria and Melguizo Alonso, Consolación and Prados Salazar, José Carlos and Ortiz Quesada, Raúl},
}