PMID- 38176243
OWN - NLM
STAT- MEDLINE
DCOM- 20240130
LR  - 20240131
IS  - 1095-7103 (Electronic)
IS  - 0021-9797 (Linking)
VI  - 659
DP  - 2024 Apr
TI  - Enhancing pancreatic ductal adenocarcinoma (PDAC) therapy with targeted carbon 
      nano-onion (CNO)-mediated delivery of gemcitabine (GEM)-derived prodrugs.
PG  - 339-354
LID - S0021-9797(23)02509-2 [pii]
LID - 10.1016/j.jcis.2023.12.166 [doi]
AB  - Nanotechnology's potential in revolutionising cancer treatments is evident in 
      targeted drug delivery systems (DDSs) engineered to optimise therapeutic efficacy 
      and minimise toxicity. This study examines a novel nanocarrier constructed with 
      carbon nano-onions (CNOs), engineered and evaluated for its ability to 
      selectively target cancer cells overexpressing the hyaluronic acid receptor; 
      CD44. Our results highlighted that the CNO-based nanocarrier coupled with 
      hyaluronic acid as the targeting agent demonstrated effective uptake by 
      CD44+ PANC-1 and MIA PaCa-2 cells, while avoiding CD44- Capan-1 cells. The 
      CNO-based nanocarrier also exhibited excellent biocompatibility in all tested 
      pancreatic ductal adenocarcinoma (PDAC) cells, as well as healthy cells. Notably, 
      the CNO-based nanocarrier was successfully loaded with chemotherapeutic 
      4-(N)-acyl- sidechain-containing prodrugs derived from gemcitabine (GEM). These 
      prodrugs alone exhibited remarkable efficacy in killing PDAC cells which are 
      known to be GEM resistant, and their efficacy was amplified when combined with 
      the CNO-based nanocarrier, particularly in targeting GEM-resistant CD44+ PDAC 
      cells. These findings demonstrate the potential of CNOs as promising scaffolds in 
      advancing targeted DDSs, signifying the translational potential of carbon 
      nanoparticles for cancer therapy.
CI  - Copyright (c) 2023 Elsevier Inc. All rights reserved.
FAU - Bartkowski, Michal
AU  - Bartkowski M
AD  - School of Chemical Sciences, Dublin City University, Glasnevin, Dublin 9, 
      Ireland.
FAU - Bincoletto, Valeria
AU  - Bincoletto V
AD  - Department of Drug Science and Technology, University of Torino, Via P. Giuria 9, 
      Torino, Italy.
FAU - Salaroglio, Iris Chiara
AU  - Salaroglio IC
AD  - Department of Oncology, University of Torino, Via Nizza 44, Torino, Italy.
FAU - Ceccone, Giacomo
AU  - Ceccone G
AD  - European Commission, Joint Research Centre, Ispra, Italy.
FAU - Arenal, Raul
AU  - Arenal R
AD  - Instituto de Nanociencia y Materiales de Aragon (INMA), CSIC-U. de Zaragoza, 
      50009 Zaragoza, Spain; Laboratorio de Microscopias Avanzadas (LMA), Universidad 
      de Zaragoza, 50018 Zaragoza, Spain; ARAID Foundation, 50018 Zaragoza, Spain.
FAU - Nervo, Sara
AU  - Nervo S
AD  - Department of Drug Science and Technology, University of Torino, Via P. Giuria 9, 
      Torino, Italy.
FAU - Rolando, Barbara
AU  - Rolando B
AD  - Department of Drug Science and Technology, University of Torino, Via P. Giuria 9, 
      Torino, Italy.
FAU - Riganti, Chiara
AU  - Riganti C
AD  - Department of Oncology, University of Torino, Via Nizza 44, Torino, Italy; 
      Molecular Biotechnology Center "Guido Tarone", University of Torino, Italy.
FAU - Arpicco, Silvia
AU  - Arpicco S
AD  - Department of Drug Science and Technology, University of Torino, Via P. Giuria 9, 
      Torino, Italy.
FAU - Giordani, Silvia
AU  - Giordani S
AD  - School of Chemical Sciences, Dublin City University, Glasnevin, Dublin 9, 
      Ireland. Electronic address: silvia.giordani@dcu.ie.
LA  - eng
PT  - Journal Article
DEP - 20231230
PL  - United States
TA  - J Colloid Interface Sci
JT  - Journal of colloid and interface science
JID - 0043125
RN  - 0 (Gemcitabine)
RN  - 0 (Prodrugs)
RN  - 0W860991D6 (Deoxycytidine)
RN  - 9004-61-9 (Hyaluronic Acid)
SB  - IM
MH  - Humans
MH  - Gemcitabine
MH  - *Prodrugs
MH  - Deoxycytidine/pharmacology/therapeutic use
MH  - Onions
MH  - Hyaluronic Acid
MH  - *Carcinoma, Pancreatic Ductal/drug therapy
MH  - *Pancreatic Neoplasms/drug therapy
MH  - Cell Line, Tumor
OTO - NOTNLM
OT  - CD44 receptor
OT  - Cancer therapy
OT  - Carbon nano-onions (CNOs)
OT  - Drug delivery systems (DDSs)
OT  - Gemcitabine (GEM)-derived prodrugs
OT  - Nanocarriers
OT  - Nanotechnology
OT  - Pancreatic adenocarcinoma (PDAC)
OT  - Targeted drug delivery
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2024/01/05 00:42
MHDA- 2024/01/30 12:43
CRDT- 2024/01/04 18:10
PHST- 2023/12/01 00:00 [received]
PHST- 2023/12/20 00:00 [revised]
PHST- 2023/12/28 00:00 [accepted]
PHST- 2024/01/30 12:43 [medline]
PHST- 2024/01/05 00:42 [pubmed]
PHST- 2024/01/04 18:10 [entrez]
AID - S0021-9797(23)02509-2 [pii]
AID - 10.1016/j.jcis.2023.12.166 [doi]
PST - ppublish
SO  - J Colloid Interface Sci. 2024 Apr;659:339-354. doi: 10.1016/j.jcis.2023.12.166. 
      Epub 2023 Dec 30.