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Triple negative breast cancer therapy with CDK1 siRNA delivered by cationic lipid assisted PEG-PLA nanoparticles.

Abstract
There is no effective clinical therapy yet for triple-negative breast cancer (TNBC) without particular human epidermal growth factor receptor-2, estrogen and progesterone receptor expression. In this study, we report a molecularly targeted and synthetic lethality-based siRNA therapy for TNBC treatment, using cationic lipid assisted poly(ethylene glycol)-b-poly(d,l-lactide) (PEG-PLA) nanoparticles as the siRNA carrier. It is demonstrated that only in c-Myc overexpressed TNBC cells, while not in normal mammary epithelial cells, delivery of siRNA targeting cyclin-dependent kinase 1 (CDK1) with the nanoparticle carrier (NPsiCDK1) induces cell viability decreasing and cell apoptosis through RNAi-mediated CDK1 expression inhibition, indicating the synthetic lethality between c-Myc with CDK1 in TNBC cells. Moreover, systemic delivery of NPsiCDK1 is able to suppress tumor growth in mice bearing SUM149 and BT549 xenograft and cause no systemic toxicity or activate the innate immune response, suggesting the therapeutic promise with such nanoparticles carrying siCDK1 for c-Myc overexpressed triple negative breast cancer.
AuthorsYang Liu, Yan-Hua Zhu, Cheng-Qiong Mao, Shuang Dou, Song Shen, Zi-Bin Tan, Jun Wang
JournalJournal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 192 Pg. 114-21 (Oct 28 2014) ISSN: 1873-4995 [Electronic] Netherlands
PMID25016158 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 Elsevier B.V. All rights reserved.
Chemical References
  • Drug Carriers
  • RNA, Small Interfering
  • monomethoxypolyethyleneglycol-polylactide block copolymer
  • Polyethylene Glycols
  • CDC2 Protein Kinase
Topics
  • Animals
  • Breast (metabolism, pathology)
  • CDC2 Protein Kinase (genetics)
  • Cell Line, Tumor
  • Drug Carriers (chemistry)
  • Female
  • Genetic Therapy
  • Humans
  • Mice
  • Nanoparticles (chemistry)
  • Polyethylene Glycols (chemistry)
  • RNA Interference
  • RNA, Small Interfering (administration & dosage, genetics, therapeutic use)
  • Triple Negative Breast Neoplasms (genetics, pathology, therapy)

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