PMID- 29957956
OWN - NLM
STAT- MEDLINE
DCOM- 20190802
LR  - 20190802
IS  - 1543-8392 (Electronic)
IS  - 1543-8384 (Linking)
VI  - 15
IP  - 9
DP  - 2018 Sep 4
TI  - CD44-Targeted Polymer-Paclitaxel Conjugates to Control the Spread and Growth of 
      Metastatic Tumors.
PG  - 3690-3699
LID - 10.1021/acs.molpharmaceut.8b00269 [doi]
AB  - One of the greatest challenges in cancer therapy is to control metastatic spread, 
      seeding, and growth of tumors in distant organs. Recently, we reported on the 
      design of a novel "drug-free" therapeutic copolymer bearing the antimigratory 
      A5G27 peptide, designated P-(A5G27)-FITC, that shows excellent specificity to 
      cancer cells overexpressing CD44v3 and CD44v6 and inhibits cancer cell migration 
      and invasion. We demonstrated that P-(A5G27)-FITC accumulated preferentially in 
      subcutaneous (sc) implanted 4T1 tumors following parenteral administration. 
      Moreover, we showed that pretreatment of mice with P-(A5G27)-FITC prior to 4T1 
      cell inoculation inhibited colonization of circulating 4T1 cells in the lungs. In 
      this study, we designed a new polymer-peptide-drug conjugate to inhibit 
      vigorously growing primary tumors and control invasive behavior of cancer cells. 
      To this end, the antimitotic drug (paclitaxel, PTX) was conjugated to 
      P-(A5G27)-FITC. The targeted polymer-drug conjugate (P-(A5G27)-PTX) was 
      significantly more toxic toward CD44-overexpressing cancer cells than the 
      nontargeted copolymer. In vivo, a single iv injection of P-(A5G27)-PTX prolonged 
      the survival of C57BL/6 mice with established B16-F10 lung metastases. When 
      injected intraperitoneally into BALB/c mice implanted sc with 4T1 tumors, 
      P-(A5G27)-PTX significantly decreased the rate of primary tumor growth, increased 
      the median survival of mice, and reduced the number of 4T1 metastases in the 
      lungs when compared to nontargeted copolymer. Most interestingly, the 
      CD44-targeted "drug-free" copolymer P-(A5G27) (without PTX) significantly 
      inhibited the rate of tumor growth and further prolonged the median survival time 
      of mice to the same extent as the PTX-containing formulations (P-(A5G27)-PTX or 
      free PTX). Overall, this study highlights the therapeutic potential of the HPMA 
      copolymer-A5G27 conjugates ("drug-free" and PTX-bearing copolymers) to control 
      the metastatic spread of cancer.
FAU - Zaiden, Michal
AU  - Zaiden M
FAU - Rutter, Marie
AU  - Rutter M
FAU - Shpirt, Lina
AU  - Shpirt L
FAU - Ventura, Yvonne
AU  - Ventura Y
FAU - Feinshtein, Valeria
AU  - Feinshtein V
FAU - David, Ayelet
AU  - David A
AUID- ORCID: 0000-0002-8929-5700
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180629
PL  - United States
TA  - Mol Pharm
JT  - Molecular pharmaceutics
JID - 101197791
RN  - 0 (CD44 protein, human)
RN  - 0 (Hyaluronan Receptors)
RN  - 0 (Polymers)
RN  - P88XT4IS4D (Paclitaxel)
MH  - Animals
MH  - Cell Line, Tumor
MH  - Cell Movement/drug effects/physiology
MH  - Cell Survival/drug effects
MH  - Drug Delivery Systems/*methods
MH  - Female
MH  - Hyaluronan Receptors/metabolism
MH  - Mammary Neoplasms, Animal/drug therapy/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Paclitaxel/*chemistry/therapeutic use
MH  - Polymers/*chemistry
OTO - NOTNLM
OT  - CD44
OT  - invasion
OT  - metastasis
OT  - paclitaxel
OT  - polymer-drug conjugates
OT  - targeted cancer therapy
EDAT- 2018/06/30 06:00
MHDA- 2019/08/03 06:00
CRDT- 2018/06/30 06:00
PHST- 2018/06/30 06:00 [pubmed]
PHST- 2019/08/03 06:00 [medline]
PHST- 2018/06/30 06:00 [entrez]
AID - 10.1021/acs.molpharmaceut.8b00269 [doi]
PST - ppublish
SO  - Mol Pharm. 2018 Sep 4;15(9):3690-3699. doi: 10.1021/acs.molpharmaceut.8b00269. 
      Epub 2018 Jun 29.