PMID- 35639628
OWN - NLM
STAT- MEDLINE
DCOM- 20220707
LR  - 20230227
IS  - 1543-8392 (Electronic)
IS  - 1543-8384 (Linking)
VI  - 19
IP  - 7
DP  - 2022 Jul 4
TI  - Codelivery of Gemcitabine and MUC1 Inhibitor Using PEG-PCL Nanoparticles for 
      Breast Cancer Therapy.
PG  - 2429-2440
LID - 10.1021/acs.molpharmaceut.2c00175 [doi]
AB  - In breast cancer therapy, Gemcitabine (Gem) is an antineoplastic antimetabolite 
      with greater anticancer efficacy and tolerability. However, effectiveness of Gem 
      is limited by its off-target effects. The synergistic potential of MUC1 (mucin 1) 
      inhibitors and Gem-loaded polymeric nanoparticles (NPs) was discussed in this 
      work in order to reduce dose-related toxicities and enhance the therapeutic 
      efficacy. The double emulsion solvent evaporation method was used to prepare 
      poly(ethylene glycol) methyl ether-block-poly-caprolactone (PEG-PCL)-loaded Gem 
      and MUC 1 inhibitor NPs. The average size of Gem and MUC 1 inhibitor-loaded NPs 
      was 128 nm, with a spherical shape. Twin-loaded NPs containing Gem and the MUC1 
      inhibitor decreased IC(50) and behaved synergistically. Furthermore, in vitro 
      mechanistic studies, that is, loss of MMP, clonogenic assay, Annexin V FITC 
      assay, and Western blotting to confirm apoptosis with simultaneous induction of 
      autophagy using acridine orange (AO) staining were performed in this study. 
      Furthermore, the investigated NPs upon combination exhibited greater loss of MMP 
      and decreased clonogenic potential with simultaneous induction of autophagy in 
      MCF-7 cells. Annexin V FITC clearly showed the percentage of apoptosis while 
      Western blotting protein expression analysis revealed an increase in caspase-3 
      activity with simultaneous decrease in Bcl-2 protein expression, a hallmark of 
      apoptosis. The effectiveness of the Ehrlich ascites solid (EAT) mice treated with 
      Gem-MUC1 inhibitor NPs was higher than that of the animals treated alone. 
      Overall, the combined administration of Gem and MUC1 inhibitor-loaded NPs was 
      found to be more efficacious than Gem and MUC1 inhibitor delivered separately.
FAU - Behl, Akanksha
AU  - Behl A
AD  - Centre for Biotechnology, Maharshi Dayanand University, Rohtak, Haryana 124 001, 
      India.
FAU - Sarwalia, Parul
AU  - Sarwalia P
AD  - Animal Biotechnology Centre, ICAR-National Dairy Research Institute, Karnal, 
      Haryana 132001, India.
FAU - Kumar, Sushil
AU  - Kumar S
AD  - Animal Biotechnology Centre, ICAR-National Dairy Research Institute, Karnal, 
      Haryana 132001, India.
FAU - Behera, Chittaranjan
AU  - Behera C
AD  - PK-PD Tox and Formulation Division, CSIR-Indian Institute of Integrative 
      Medicine, Jammu 180001, India.
FAU - Mintoo, Mubashir Javed
AU  - Mintoo MJ
AD  - Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, 
      Jammu 180001, India.
FAU - Datta, Tirtha Kumar
AU  - Datta TK
AD  - Animal Biotechnology Centre, ICAR-National Dairy Research Institute, Karnal, 
      Haryana 132001, India.
FAU - Gupta, Prem N
AU  - Gupta PN
AD  - PK-PD Tox and Formulation Division, CSIR-Indian Institute of Integrative 
      Medicine, Jammu 180001, India.
FAU - Chhillar, Anil K
AU  - Chhillar AK
AUID- ORCID: 0000-0003-3911-9394
AD  - Centre for Biotechnology, Maharshi Dayanand University, Rohtak, Haryana 124 001, 
      India.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220531
PL  - United States
TA  - Mol Pharm
JT  - Molecular pharmaceutics
JID - 101197791
RN  - 0 (Annexin A5)
RN  - 0 (MUC1 protein, human)
RN  - 0 (Mucin-1)
RN  - 0 (Polyesters)
RN  - 0W860991D6 (Deoxycytidine)
RN  - 24980-41-4 (polycaprolactone)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - I223NX31W9 (Fluorescein-5-isothiocyanate)
RN  - 0 (Gemcitabine)
SB  - IM
CIN - Mol Pharm. 2023 Feb 6;20(2):1447-1448. PMID: 36576337
MH  - Animals
MH  - Annexin A5/therapeutic use
MH  - *Breast Neoplasms/drug therapy
MH  - Cell Line, Tumor
MH  - Deoxycytidine/analogs & derivatives
MH  - Female
MH  - Fluorescein-5-isothiocyanate
MH  - Humans
MH  - Mice
MH  - Mucin-1
MH  - *Nanoparticles
MH  - Polyesters
MH  - Polyethylene Glycols
MH  - Gemcitabine
OTO - NOTNLM
OT  - MUC1 inhibitor
OT  - apoptosis
OT  - autophagy
OT  - gemcitabine
OT  - nanoparticles
EDAT- 2022/06/01 06:00
MHDA- 2022/07/08 06:00
CRDT- 2022/05/31 16:06
PHST- 2022/06/01 06:00 [pubmed]
PHST- 2022/07/08 06:00 [medline]
PHST- 2022/05/31 16:06 [entrez]
AID - 10.1021/acs.molpharmaceut.2c00175 [doi]
PST - ppublish
SO  - Mol Pharm. 2022 Jul 4;19(7):2429-2440. doi: 10.1021/acs.molpharmaceut.2c00175. 
      Epub 2022 May 31.