PMID- 28605176
OWN - NLM
STAT- MEDLINE
DCOM- 20180402
LR  - 20220311
IS  - 1526-4602 (Electronic)
IS  - 1525-7797 (Linking)
VI  - 18
IP  - 7
DP  - 2017 Jul 10
TI  - Reduction- and pH-Sensitive Hyaluronan Nanoparticles for Delivery of Iridium(III) 
      Anticancer Drugs.
PG  - 2102-2117
LID - 10.1021/acs.biomac.7b00445 [doi]
AB  - The organoiridium(III) complex (Ir(III)) [(eta(5)-Cp(xbiph))Ir(phpy) (py)]PF(6) 
      containing pi-bonded biphenyltetramethylcyclopentadienyl(Cp(xbiph)), CwedgeN-chelated 
      phenylpyridine(phpy), and pyridine (py) ligands has more potent antitumor 
      activity as a new generation of drug than cisplatin toward various cancer cells. 
      However, poor site-specific delivery, low solubility, and poor tumor penetration 
      are common limitations of chemotherapy drugs. To develop CD44-targetable, pH-, 
      and reduction-responsive drug delivery systems for Ir(III) drugs, the amphiphilic 
      hyaluronan (HA)-based conjugates of HA-cystamin-pyrenyl (HA-ss-Py) containing 
      disulfide bonds and HA-pyrenyl (HA-Py) were designed. The Ir(III) drug was 
      readily loaded into these two amphiphilic conjugates and nanoparticles were 
      formed. Dynamic light scattering (DLS) studies showed that the micelles formed 
      from HA-ss-Py were sufficiently stable under physiological conditions, but were 
      prone to rapid dissociation in reducing environments (20 mM glutathione (GSH)). 
      In subsequent confocal microscopy analyses, A549 cancer cells efficiently 
      internalized HA-based micelles. Moreover, in vitro cytotoxicity assays in A549 
      cells demonstrat that Ir-loaded HA-based nanoparticles have higher cytotoxicity 
      than the free Ir(III) anticancer drug. Finally, systemic administration of 
      Ir(III)-loaded HA-ss-Py nanoparticles enhanced tumor inhibition in vivo, and the 
      corresponding biodistribution experiments showed that HA-ss-Py micelles 
      accumulate in tumors. Overall, our results suggest that HA-ss-Py micelles have a 
      great potential to be used as an effective Ir(III) drug carrier for targeted 
      cancer therapy.
FAU - Cai, Zhixiang
AU  - Cai Z
AD  - Department of Polymer Science and Engineering, School of Chemistry and Chemical 
      Engineering, Shanghai Jiao Tong University , Shanghai, 200240, China.
FAU - Zhang, Hongbin
AU  - Zhang H
AUID- ORCID: 0000-0002-4419-4818
AD  - Department of Polymer Science and Engineering, School of Chemistry and Chemical 
      Engineering, Shanghai Jiao Tong University , Shanghai, 200240, China.
FAU - Wei, Yue
AU  - Wei Y
AD  - Department of Polymer Science and Engineering, School of Chemistry and Chemical 
      Engineering, Shanghai Jiao Tong University , Shanghai, 200240, China.
FAU - Wei, Yuanyuan
AU  - Wei Y
AD  - Department of Polymer Science and Engineering, School of Chemistry and Chemical 
      Engineering, Shanghai Jiao Tong University , Shanghai, 200240, China.
FAU - Xie, Yanping
AU  - Xie Y
AD  - Department of Polymer Science and Engineering, School of Chemistry and Chemical 
      Engineering, Shanghai Jiao Tong University , Shanghai, 200240, China.
FAU - Cong, Fengsong
AU  - Cong F
AD  - Department of Biochemistry and Molecular Biology, School of life Sciences and 
      Biotechnology, Shanghai Jiao Tong University , Shanghai, 200240, China.
LA  - eng
PT  - Journal Article
DEP - 20170622
PL  - United States
TA  - Biomacromolecules
JT  - Biomacromolecules
JID - 100892849
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Delayed-Action Preparations)
RN  - 0 (Organometallic Compounds)
RN  - 44448S9773 (Iridium)
RN  - 9004-61-9 (Hyaluronic Acid)
SB  - IM
MH  - A549 Cells
MH  - *Antineoplastic Agents/chemical synthesis/chemistry/pharmacology
MH  - Delayed-Action Preparations/chemical synthesis/chemistry/pharmacology
MH  - Humans
MH  - *Hyaluronic Acid/chemistry/pharmacology
MH  - Hydrogen-Ion Concentration
MH  - *Iridium/chemistry/pharmacology
MH  - Neoplasms/*drug therapy/metabolism/pathology
MH  - *Organometallic Compounds/chemical synthesis/chemistry/pharmacology
EDAT- 2017/06/13 06:00
MHDA- 2018/04/03 06:00
CRDT- 2017/06/13 06:00
PHST- 2017/06/13 06:00 [pubmed]
PHST- 2018/04/03 06:00 [medline]
PHST- 2017/06/13 06:00 [entrez]
AID - 10.1021/acs.biomac.7b00445 [doi]
PST - ppublish
SO  - Biomacromolecules. 2017 Jul 10;18(7):2102-2117. doi: 10.1021/acs.biomac.7b00445. 
      Epub 2017 Jun 22.