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Effect of Oxaliplatin-Loaded Poly (d,l-Lactide-co-Glycolic Acid) (PLGA) Nanoparticles Combined with Retinoic Acid and Cholesterol on Apoptosis, Drug Resistance, and Metastasis Factors of Colorectal Cancer

Identifieur interne : 000166 ( an2020/Analysis ); précédent : 000165; suivant : 000167

Effect of Oxaliplatin-Loaded Poly (d,l-Lactide-co-Glycolic Acid) (PLGA) Nanoparticles Combined with Retinoic Acid and Cholesterol on Apoptosis, Drug Resistance, and Metastasis Factors of Colorectal Cancer

Auteurs : Ana Luiza C. De S. L. Oliveira ; Raimundo Fernandes De Araújo Júnior [Brésil] ; Thaís Gomes De Carvalho ; Alan B. Chan ; Timo Schomann ; Filippo Tamburini ; Lioe-Fee De Geus-Oei ; Luis J. Cruz

Source :

RBID : PMC:7076533

Abstract

Apoptosis signaling pathways, drug resistance, and metastasis are important targets to develop new cancer treatments. We developed cholesterol-coated Poly(d,l-Lactide-co-Glycolic Acid) (PLGA) nanoparticles for effective encapsulation and delivery of retinoic acid and oxaliplatin to analyze their antitumor activity in colorectal cancer. The cell viability and proliferation of tumoral cells lines (CT-26 and SW-480) decreased when compared to control in vitro after treatment with the nanoparticles. In addition, apoptosis of CT-26 cells increased. Importantly, cytoprotection of nontumor cells was detected. Expression of pro-apoptotic proteins was upregulated, while anti-apoptotic proteins were downregulated either in vitro or in vivo. In addition, drug resistance and metastasis factors were downregulated in vivo. Human colorectal tumors that highly expressed BCL-2 and Ki-67 had a greater tendency towards death within 60 months. Our results show that loading oxaliplatin combined with retinoic acid and cholesterol in a nanoparticle formulation enables determination of optimal antitumor activity and subsequent treatment efficacy.


Url:
DOI: 10.3390/pharmaceutics12020193
PubMed: 32102251
PubMed Central: 7076533


Affiliations:


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PMC:7076533

Le document en format XML

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<email>tambu.91@hotmail.it</email>
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<name sortKey="De Geus Oei, Lioe Fee" sort="De Geus Oei, Lioe Fee" uniqKey="De Geus Oei L" first="Lioe-Fee" last="De Geus-Oei">Lioe-Fee De Geus-Oei</name>
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<nlm:aff id="af5-pharmaceutics-12-00193">Nuclear Medicine, Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands;
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</nlm:aff>
</affiliation>
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<name sortKey="J Cruz, Luis" sort="J Cruz, Luis" uniqKey="J Cruz L" first="Luis" last="J. Cruz">Luis J. Cruz</name>
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<nlm:aff id="af2-pharmaceutics-12-00193">Translational Nanobiomaterials and Imaging, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands;
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<p>Apoptosis signaling pathways, drug resistance, and metastasis are important targets to develop new cancer treatments. We developed cholesterol-coated Poly(
<sc>d</sc>
,
<sc>l</sc>
-Lactide-
<italic>co</italic>
-Glycolic Acid) (PLGA) nanoparticles for effective encapsulation and delivery of retinoic acid and oxaliplatin to analyze their antitumor activity in colorectal cancer. The cell viability and proliferation of tumoral cells lines (CT-26 and SW-480) decreased when compared to control in vitro after treatment with the nanoparticles. In addition, apoptosis of CT-26 cells increased. Importantly, cytoprotection of nontumor cells was detected. Expression of pro-apoptotic proteins was upregulated, while anti-apoptotic proteins were downregulated either in vitro or in vivo. In addition, drug resistance and metastasis factors were downregulated in vivo. Human colorectal tumors that highly expressed BCL-2 and Ki-67 had a greater tendency towards death within 60 months. Our results show that loading oxaliplatin combined with retinoic acid and cholesterol in a nanoparticle formulation enables determination of optimal antitumor activity and subsequent treatment efficacy.</p>
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<affiliations>
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</affiliations>
</record>

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