PMID- 31534547
OWN - NLM
STAT- MEDLINE
DCOM- 20200928
LR  - 20200928
IS  - 1838-7640 (Electronic)
IS  - 1838-7640 (Linking)
VI  - 9
IP  - 21
DP  - 2019
TI  - A nano-liposome formulation of the PARP inhibitor Talazoparib enhances treatment 
      efficacy and modulates immune cell populations in mammary tumors of 
      BRCA-deficient mice.
PG  - 6224-6238
LID - 10.7150/thno.36281 [doi]
AB  - Two recently approved PARP inhibitors provide an important new therapeutic option 
      for patients with BRCA-mutated metastatic breast cancer. PARP inhibitors 
      significantly prolong progression-free survival in patients, but conventional 
      oral delivery of PARP inhibitors is hindered by limited bioavailability and 
      off-target toxicities, thus compromising the therapeutic benefits and quality of 
      life for patients. Here, we developed a new delivery system, in which the PARP 
      inhibitor Talazoparib is encapsulated in the bilayer of a nano-liposome, to 
      overcome these limitations. Methods: Nano-Talazoparib (NanoTLZ) was characterized 
      both in vitro and in vivo. The therapeutic efficacy and toxicity of 
      Nano-Talazoparib (NanoTLZ) were evaluated in BRCA-deficient mice. The regulation 
      of NanoTLZ on gene transcription and immunomodulation were further investigated 
      in spontaneous BRCA-deficient tumors. Results: NanoTLZ significantly (p<0.05) 
      prolonged the overall survival of BRCA-deficient mice compared to all of the 
      other experimental groups, including saline control, empty nanoparticles, and 
      free Talazoparib groups (oral and i.v.). Moreover, NanoTLZ was better tolerated 
      than treatment with free Talazoparib, with no significant weight lost or alopecia 
      as was observed with the free drug. After 5 doses, NanoTLZ altered the expression 
      of over 140 genes and induced DNA damage, cell cycle arrest and inhibition of 
      cell proliferation in the tumor. In addition, NanoTLZ favorably modulated immune 
      cell populations in vivo and significantly (p<0.05) decreased the percentage of 
      myeloid derived suppressor cells in both the tumor and spleen compared to control 
      groups. Conclusions: Our results demonstrate that delivering nanoformulated 
      Talazoparib not only enhances treatment efficacy but also reduces off-target 
      toxicities in BRCA-deficient mice; the same potential is predicted for patients 
      with BRCA-deficient breast cancer.
FAU - Zhang, Di
AU  - Zhang D
AD  - Michigan State University, East Lansing, MI, USA.
FAU - Baldwin, Paige
AU  - Baldwin P
AD  - Northeastern University, Boston, MA, USA.
FAU - Leal, Ana S
AU  - Leal AS
AD  - Michigan State University, East Lansing, MI, USA.
FAU - Carapellucci, Sarah
AU  - Carapellucci S
AD  - Michigan State University, East Lansing, MI, USA.
FAU - Sridhar, Srinivas
AU  - Sridhar S
AD  - Northeastern University, Boston, MA, USA.
AD  - Harvard Medical School, Boston, MA, USA.
FAU - Liby, Karen T
AU  - Liby KT
AD  - Michigan State University, East Lansing, MI, USA.
LA  - eng
GR  - T32 GM092715/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20190814
PL  - Australia
TA  - Theranostics
JT  - Theranostics
JID - 101552395
RN  - 0 (Antineoplastic Agents)
RN  - 0 (BRCA1 Protein)
RN  - 0 (BRCA2 Protein)
RN  - 0 (BRCA2 protein, mouse)
RN  - 0 (Brca1 protein, mouse)
RN  - 0 (Liposomes)
RN  - 0 (Phthalazines)
RN  - 0 (Poly(ADP-ribose) Polymerase Inhibitors)
RN  - 9QHX048FRV (talazoparib)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*administration & dosage
MH  - BRCA1 Protein/genetics
MH  - BRCA2 Protein/genetics
MH  - Breast Neoplasms/*drug therapy
MH  - Drug Compounding
MH  - Female
MH  - Humans
MH  - Immunomodulation
MH  - Liposomes/*administration & dosage
MH  - Mammary Neoplasms, Experimental/*drug therapy
MH  - Mice
MH  - Nanoparticles/*administration & dosage
MH  - Phthalazines
MH  - Poly(ADP-ribose) Polymerase Inhibitors/*administration & dosage
MH  - Treatment Outcome
PMC - PMC6735511
OTO - NOTNLM
OT  - BRCA-deficient breast cancer
OT  - Nanoparticle
OT  - PARP inhibitor
OT  - Talazoparib
OT  - immunomodulation
COIS- Competing Interests: NanoTalazoparib is part of the subject matter and 
      intellectual property in a patent application assigned to Northeastern 
      University.
EDAT- 2019/09/20 06:00
MHDA- 2020/09/29 06:00
PMCR- 2019/01/01
CRDT- 2019/09/20 06:00
PHST- 2019/05/03 00:00 [received]
PHST- 2019/07/22 00:00 [accepted]
PHST- 2019/09/20 06:00 [entrez]
PHST- 2019/09/20 06:00 [pubmed]
PHST- 2020/09/29 06:00 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - thnov09p6224 [pii]
AID - 10.7150/thno.36281 [doi]
PST - epublish
SO  - Theranostics. 2019 Aug 14;9(21):6224-6238. doi: 10.7150/thno.36281. eCollection 
      2019.