Detail
Article
Online article
FT
Medvik - BMC
  • Something wrong with this record ?

One-Step Synthesis of Nanoliposomal Copper Diethyldithiocarbamate and Its Assessment for Cancer Therapy

RA. Paun, DC. Dumut, A. Centorame, T. Thuraisingam, M. Hajduch, M. Mistrik, P. Dzubak, JB. De Sanctis, D. Radzioch, M. Tabrizian

. 2022 ; 14 (3) : . [pub] 20220314

Language English Country Switzerland

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc22009792

Grant support
TIPS- CRC-232667 Canada Research Chairs

The metal complex copper diethyldithiocarbamate (CuET) induces cancer cell death by inhibiting protein degradation and induces proteotoxic stress, making CuET a promising cancer therapeutic. However, no clinical formulation of CuET exists to date as the drug is insoluble in water and exhibits poor bioavailability. To develop a scalable formulation, nanoliposomal (LP) CuET was synthesized using ethanol injection as a facile one-step method that is suitable for large-scale manufacturing. The nanoparticles are monodispersed, colloidally stable, and approximately 100 nm in diameter with an encapsulation efficiency of over 80%. LP-CuET demonstrates excellent stability in plasma, minimal size change, and little drug release after six-month storage at various temperatures. Additionally, melanoma cell lines exhibit significant sensitivity to LP-CuET and cellular uptake occurs predominantly through endocytosis in YUMM 1.7 cancer cells. Intracellular drug delivery is mediated by vesicle acidification with more nanoparticles being internalized by melanoma cells compared with RAW 264.7 macrophages. Additionally, the nanoparticles preferentially accumulate in YUMM 1.7 tumors where they induce cancer cell death in vivo. The development and characterization of a stable and scalable CuET formulation illustrated in this study fulfils the requirements needed for a potent clinical grade formulation.

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc22009792
003      
CZ-PrNML
005      
20220425131552.0
007      
ta
008      
220420s2022 sz f 000 0|eng||
009      
AR
024    7_
$a 10.3390/pharmaceutics14030640 $2 doi
035    __
$a (PubMed)35336014
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a sz
100    1_
$a Paun, Radu A $u Department of Biomedical Engineering, Faculty of Medicine and Health Sciences, McGill University, 3775 Rue University, Montreal, QC H3A 2B6, Canada $u Research Institute of the McGill University Health Centre, 1001 Decarie Blvd, Montreal, QC H4A 3J1, Canada $1 https://orcid.org/0000000345608995
245    10
$a One-Step Synthesis of Nanoliposomal Copper Diethyldithiocarbamate and Its Assessment for Cancer Therapy / $c RA. Paun, DC. Dumut, A. Centorame, T. Thuraisingam, M. Hajduch, M. Mistrik, P. Dzubak, JB. De Sanctis, D. Radzioch, M. Tabrizian
520    9_
$a The metal complex copper diethyldithiocarbamate (CuET) induces cancer cell death by inhibiting protein degradation and induces proteotoxic stress, making CuET a promising cancer therapeutic. However, no clinical formulation of CuET exists to date as the drug is insoluble in water and exhibits poor bioavailability. To develop a scalable formulation, nanoliposomal (LP) CuET was synthesized using ethanol injection as a facile one-step method that is suitable for large-scale manufacturing. The nanoparticles are monodispersed, colloidally stable, and approximately 100 nm in diameter with an encapsulation efficiency of over 80%. LP-CuET demonstrates excellent stability in plasma, minimal size change, and little drug release after six-month storage at various temperatures. Additionally, melanoma cell lines exhibit significant sensitivity to LP-CuET and cellular uptake occurs predominantly through endocytosis in YUMM 1.7 cancer cells. Intracellular drug delivery is mediated by vesicle acidification with more nanoparticles being internalized by melanoma cells compared with RAW 264.7 macrophages. Additionally, the nanoparticles preferentially accumulate in YUMM 1.7 tumors where they induce cancer cell death in vivo. The development and characterization of a stable and scalable CuET formulation illustrated in this study fulfils the requirements needed for a potent clinical grade formulation.
655    _2
$a časopisecké články $7 D016428
700    1_
$a Dumut, Daciana C $u Research Institute of the McGill University Health Centre, 1001 Decarie Blvd, Montreal, QC H4A 3J1, Canada $u Division of Experimental Medicine, Faculty of Medicine and Health Sciences, McGill University, 1001 Decarie Blvd, Montreal, QC H4A 3J1, Canada
700    1_
$a Centorame, Amanda $u Research Institute of the McGill University Health Centre, 1001 Decarie Blvd, Montreal, QC H4A 3J1, Canada $u Division of Experimental Medicine, Faculty of Medicine and Health Sciences, McGill University, 1001 Decarie Blvd, Montreal, QC H4A 3J1, Canada
700    1_
$a Thuraisingam, Thusanth $u Division of Dermatology, Department of Medicine, Jewish General Hospital, McGill University, 3755 Cote Ste-Catherine, Montreal, QC H3T 1E2, Canada $u Division of Dermatology, Department of Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, ON K1H 8M5, Canada
700    1_
$a Hajduch, Marian $u Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, Hnevotinska 1333/5, 77900 Olomouc, Czech Republic $u Czech Advanced Technology and Research Institute, Palacky University Olomouc, Krizkovskeho 511/8, 77900 Olomouc, Czech Republic $1 https://orcid.org/000000024834908X $7 xx0050218
700    1_
$a Mistrik, Martin $u Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, Hnevotinska 1333/5, 77900 Olomouc, Czech Republic $u Czech Advanced Technology and Research Institute, Palacky University Olomouc, Krizkovskeho 511/8, 77900 Olomouc, Czech Republic $1 https://orcid.org/0000000223210348
700    1_
$a Dzubak, Petr $u Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, Hnevotinska 1333/5, 77900 Olomouc, Czech Republic $u Czech Advanced Technology and Research Institute, Palacky University Olomouc, Krizkovskeho 511/8, 77900 Olomouc, Czech Republic $1 https://orcid.org/0000000230985969 $7 xx0080445
700    1_
$a De Sanctis, Juan B $u Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, Hnevotinska 1333/5, 77900 Olomouc, Czech Republic $u Czech Advanced Technology and Research Institute, Palacky University Olomouc, Krizkovskeho 511/8, 77900 Olomouc, Czech Republic
700    1_
$a Radzioch, Danuta $u Research Institute of the McGill University Health Centre, 1001 Decarie Blvd, Montreal, QC H4A 3J1, Canada $u Division of Experimental Medicine, Faculty of Medicine and Health Sciences, McGill University, 1001 Decarie Blvd, Montreal, QC H4A 3J1, Canada
700    1_
$a Tabrizian, Maryam $u Department of Biomedical Engineering, Faculty of Medicine and Health Sciences, McGill University, 3775 Rue University, Montreal, QC H3A 2B6, Canada $u Faculty of Dentistry and Oral Health Sciences, McGill University, 3640 Rue University, Montreal, QC H3A 0C7, Canada
773    0_
$w MED00186380 $t Pharmaceutics $x 1999-4923 $g Roč. 14, č. 3 (2022)
856    41
$u https://pubmed.ncbi.nlm.nih.gov/35336014 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y - $z 0
990    __
$a 20220420 $b ABA008
991    __
$a 20220425131550 $b ABA008
999    __
$a ind $b bmc $g 1784397 $s 1160990
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2022 $b 14 $c 3 $e 20220314 $i 1999-4923 $m Pharmaceutics $n Pharmaceutics $x MED00186380
GRA    __
$a TIPS- CRC-232667 $p Canada Research Chairs
LZP    __
$a Pubmed-20220420

Find record

Citation metrics

Archiving options