PMID- 32278056
OWN - NLM
STAT- MEDLINE
DCOM- 20210218
LR  - 20211204
IS  - 1873-3476 (Electronic)
IS  - 0378-5173 (Linking)
VI  - 582
DP  - 2020 May 30
TI  - Folate decorated polymeric micelles for targeted delivery of the kinase inhibitor 
      dactolisib to cancer cells.
PG  - 119305
LID - S0378-5173(20)30289-1 [pii]
LID - 10.1016/j.ijpharm.2020.119305 [doi]
AB  - One of the main challenges in clinical translation of polymeric micelles is 
      retention of the drug in the nanocarrier system upon its systemic administration. 
      Core crosslinking and coupling of the drug to the micellar backbone are common 
      strategies to overcome these issues. In the present study, polymeric micelles 
      were prepared for tumor cell targeting of the kinase inhibitor dactolisib which 
      inhibits both the mammalian Target of Rapamycin (mTOR) kinase and 
      phosphatidylinositol-3-kinase (PI3K). We employed platinum(II)-based linker 
      chemistry to couple dactolisib to the core of poly(ethylene 
      glycol)-b-poly(acrylic acid) (PEG-b-PAA) polymeric micelles. The formed 
      dactolisib-PEG-PAA unimers are amphiphilic and self-assemble in an aqueous milieu 
      into core-shell polymeric micelles. Folate was conjugated onto the surface of the 
      micelles to yield folate-decorated polymeric micelles which can target folate 
      receptor over-expressing tumor cells. Fluorescently labeled polymeric micelles 
      were prepared using a lissamine-platinum complex linked in a similar manner as 
      dactolisib. Dactolisib polymeric micelles showed good colloidal stability in 
      water and released the coupled drug in buffers containing chloride or 
      glutathione. Folate decorated micelles were avidly internalized by 
      folate-receptor-positive KB cells and displayed targeted cellular cytotoxicity at 
      50-75 nM IC(50). In conclusion, we have prepared a novel type of folate-receptor 
      targeted polymeric micelles in which platinum(II) linker chemistry modulates drug 
      retention and sustained release of the coupled inhibitor dactolisib.
CI  - Copyright (c) 2020 Elsevier B.V. All rights reserved.
FAU - Shi, Haili
AU  - Shi H
AD  - Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, 
      Utrecht University, the Netherlands.
FAU - van Steenbergen, Mies J
AU  - van Steenbergen MJ
AD  - Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, 
      Utrecht University, the Netherlands.
FAU - Lou, Bo
AU  - Lou B
AD  - Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, 
      Utrecht University, the Netherlands.
FAU - Liu, Yanna
AU  - Liu Y
AD  - Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, 
      Utrecht University, the Netherlands.
FAU - Hennink, Wim E
AU  - Hennink WE
AD  - Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, 
      Utrecht University, the Netherlands.
FAU - Kok, Robbert J
AU  - Kok RJ
AD  - Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, 
      Utrecht University, the Netherlands. Electronic address: r.j.kok@uu.nl.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20200408
PL  - Netherlands
TA  - Int J Pharm
JT  - International journal of pharmaceutics
JID - 7804127
RN  - 0 (Acrylic Resins)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Drug Carriers)
RN  - 0 (Folic Acid Transporters)
RN  - 0 (Imidazoles)
RN  - 0 (Micelles)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Quinolines)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - 4Q93RCW27E (carbopol 940)
RN  - 935E97BOY8 (Folic Acid)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - RUJ6Z9Y0DT (dactolisib)
SB  - IM
MH  - A549 Cells
MH  - Acrylic Resins/*chemistry
MH  - Antineoplastic Agents/chemistry/metabolism/*pharmacology
MH  - Cell Survival
MH  - *Drug Carriers
MH  - Drug Compounding
MH  - Drug Liberation
MH  - Drug Stability
MH  - Folic Acid/chemistry/*metabolism
MH  - Folic Acid Transporters/metabolism
MH  - Humans
MH  - Imidazoles/chemistry/metabolism/*pharmacology
MH  - Lung Neoplasms/*drug therapy/enzymology/pathology
MH  - Micelles
MH  - Phosphoinositide-3 Kinase Inhibitors/chemistry/metabolism/*pharmacology
MH  - Polyethylene Glycols/*chemistry
MH  - Quinolines/chemistry/metabolism/*pharmacology
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/metabolism
OTO - NOTNLM
OT  - Cancer
OT  - Coordination chemistry
OT  - Dactolisib
OT  - Folate
OT  - Polymeric micelles
OT  - Signal transduction inhibitor
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- 2020/04/12 06:00
MHDA- 2021/02/20 06:00
CRDT- 2020/04/12 06:00
PHST- 2020/01/10 00:00 [received]
PHST- 2020/04/02 00:00 [revised]
PHST- 2020/04/03 00:00 [accepted]
PHST- 2020/04/12 06:00 [pubmed]
PHST- 2021/02/20 06:00 [medline]
PHST- 2020/04/12 06:00 [entrez]
AID - S0378-5173(20)30289-1 [pii]
AID - 10.1016/j.ijpharm.2020.119305 [doi]
PST - ppublish
SO  - Int J Pharm. 2020 May 30;582:119305. doi: 10.1016/j.ijpharm.2020.119305. Epub 
      2020 Apr 8.