PMID- 36850263
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230301
IS  - 2073-4360 (Electronic)
IS  - 2073-4360 (Linking)
VI  - 15
IP  - 4
DP  - 2023 Feb 16
TI  - WZB117 Decorated Metformin-Carboxymethyl Chitosan Nanoparticles for Targeting 
      Breast Cancer Metabolism.
LID - 10.3390/polym15040976 [doi]
LID - 976
AB  - The "Warburg effect" provides a novel method for treating cancer cell metabolism. 
      Overexpression of glucose transporter 1 (GLUT1), activation of AMP-activated 
      protein kinase (AMPK), and downregulation of mammalian target of rapamycin (mTOR) 
      have been identified as biomarkers of abnormal cancer cell metabolism. Metformin 
      (MET) is an effective therapy for breast cancer (BC), but its efficacy is largely 
      reliant on the concentration of glucose at the tumor site. We propose a WZB117 (a 
      GLUT1 inhibitor)-OCMC (O-carboxymethyl-chitosan)-MET combo strategy for 
      simultaneous GLUT1 and mTOR targeting for alteration of BC metabolism. WZB117 
      conjugated polymeric nanoparticles were 225.67 +/- 11.5 nm in size, with a PDI of 
      0.113 +/- 0.16, and an encapsulation of 72.78 6.4%. OCMC pH-dependently and 
      selectively releases MET at the tumor site. MET targets the mTOR pathway in 
      cancer cells, and WZB117 targets BCL2 to alter GLUT1 at the cancer site. 
      WZB117-OCMC-MET overcomes the limitations of MET monotherapy by targeting mTOR 
      and BCL2 synergistically. WZB117-OCMC-MET activates AMPK and suppresses mTOR in a 
      Western blot experiment, indicating growth-inhibitory and apoptotic 
      characteristics. AO/EB and the cell cycle enhance cellular internalization as 
      compared to MET alone. WZB117-OCMC-MET affects cancer cells' metabolism and is a 
      promising BC therapeutic strategy.
FAU - De, Anindita
AU  - De A
AUID- ORCID: 0000-0002-0838-9474
AD  - College of Pharmacy, Gachon Institute of Pharmaceutical Science, Gachon 
      University, Incheon 21936, Republic of Korea.
FAU - Wadhwani, Ashish
AU  - Wadhwani A
AUID- ORCID: 0000-0001-8102-9486
AD  - Faculty of Health Sciences, School of Pharmacy, JSS Academy of Higher Education 
      and Research, Mauritius, Droopnath Ramphul St, Vacoas-Phoenix 73304, Mauritius.
FAU - Sauraj
AU  - Sauraj
AD  - College of Pharmacy, Gachon Institute of Pharmaceutical Science, Gachon 
      University, Incheon 21936, Republic of Korea.
FAU - Roychowdhury, Parikshit
AU  - Roychowdhury P
AD  - Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher 
      Education and Research, Ooty 643001, Tamil Nadu, India.
FAU - Kang, Ji Hee
AU  - Kang JH
AD  - College of Pharmacy, Gachon Institute of Pharmaceutical Science, Gachon 
      University, Incheon 21936, Republic of Korea.
FAU - Ko, Young Tag
AU  - Ko YT
AUID- ORCID: 0000-0002-6389-2507
AD  - College of Pharmacy, Gachon Institute of Pharmaceutical Science, Gachon 
      University, Incheon 21936, Republic of Korea.
FAU - Kuppusamy, Gowthamarajan
AU  - Kuppusamy G
AD  - Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher 
      Education and Research, Ooty 643001, Tamil Nadu, India.
LA  - eng
PT  - Journal Article
DEP - 20230216
PL  - Switzerland
TA  - Polymers (Basel)
JT  - Polymers
JID - 101545357
PMC - PMC9962472
OTO - NOTNLM
OT  - WZB117
OT  - breast cancer metabolism
OT  - conjugation
OT  - in vitro cancer efficacy
OT  - metformin
COIS- The authors declare no conflict of interest.
EDAT- 2023/03/01 06:00
MHDA- 2023/03/01 06:01
PMCR- 2023/02/16
CRDT- 2023/02/28 01:12
PHST- 2023/01/04 00:00 [received]
PHST- 2023/02/04 00:00 [revised]
PHST- 2023/02/14 00:00 [accepted]
PHST- 2023/02/28 01:12 [entrez]
PHST- 2023/03/01 06:00 [pubmed]
PHST- 2023/03/01 06:01 [medline]
PHST- 2023/02/16 00:00 [pmc-release]
AID - polym15040976 [pii]
AID - polymers-15-00976 [pii]
AID - 10.3390/polym15040976 [doi]
PST - epublish
SO  - Polymers (Basel). 2023 Feb 16;15(4):976. doi: 10.3390/polym15040976.