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Polymer-lipid hybrid nanoparticles synchronize pharmacokinetics of co-encapsulated doxorubicin-mitomycin C and enable their spatiotemporal co-delivery and local bioavailability in breast tumor.

Publication ,  Journal Article
Zhang, RX; Cai, P; Zhang, T; Chen, K; Li, J; Cheng, J; Pang, KS; Adissu, HA; Rauth, AM; Wu, XY
Published in: Nanomedicine
July 2016

UNLABELLED: Effective combination chemotherapy requires the delivery of drugs of synergism to tumor sites while sparing normal tissues. Herein we investigated whether coencapsulation of doxorubicin and mitomycin C within polymer-lipid hybrid nanoparticles (DMPLN) achieved this goal via ratiometric drugs in an orthotopic murine breast tumor model with nanocarrier-modified biodistribution, pharmacokinetics, local bioavailability and toxicity. Fluorescence imaging revealed quickened and extended tumor uptake but reduced cardiac accumulation of DMPLN. Quantitative drug analysis demonstrated prolonged systemic circulation, increased tumor accumulation and sustained synergistic ratios of doxorubicin and mitomycin C delivered by DMPLN over 24h. Higher levels of tumor cell apoptosis and reduced organ toxicity were obtained with DMPLN compared to free drug cocktails. DMPLN released DOX in tumors more efficiently than that from liposomal doxorubicin, as evidenced by a higher extent of the metabolite, doxorubicinol. These findings substantiate the importance of rational design of nanoparticles for synergistic drug combination therapy. FROM THE CLINICAL EDITOR: The treatment of cancer usually involves using combination chemotherapeutic agents. In adopting a nanomedicine approach, one can in theory design combination therapy consisting of drugs of synergistic activities, with the aim to target tumor specifically while minimizing systemic toxicity. The authors in this study provided evidence for this rational design by co-encapsulation of doxorubicin and mitomycin C within polymer-lipid hybrid nanoparticles (DMPLN) in a breast cancer model.

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Published In

Nanomedicine

DOI

EISSN

1549-9642

Publication Date

July 2016

Volume

12

Issue

5

Start / End Page

1279 / 1290

Location

United States

Related Subject Headings

  • Tissue Distribution
  • Polymers
  • Nanoscience & Nanotechnology
  • Nanoparticles
  • Mitomycin
  • Mice
  • Lipids
  • Humans
  • Drug Synergism
  • Drug Resistance, Neoplasm
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Zhang, R. X., Cai, P., Zhang, T., Chen, K., Li, J., Cheng, J., … Wu, X. Y. (2016). Polymer-lipid hybrid nanoparticles synchronize pharmacokinetics of co-encapsulated doxorubicin-mitomycin C and enable their spatiotemporal co-delivery and local bioavailability in breast tumor. Nanomedicine, 12(5), 1279–1290. https://doi.org/10.1016/j.nano.2015.12.383
Zhang, Rui Xue, Ping Cai, Tian Zhang, King Chen, Jason Li, Ji Cheng, K Sandy Pang, Hibret A. Adissu, Andrew M. Rauth, and Xiao Yu Wu. “Polymer-lipid hybrid nanoparticles synchronize pharmacokinetics of co-encapsulated doxorubicin-mitomycin C and enable their spatiotemporal co-delivery and local bioavailability in breast tumor.Nanomedicine 12, no. 5 (July 2016): 1279–90. https://doi.org/10.1016/j.nano.2015.12.383.
Journal cover image

Published In

Nanomedicine

DOI

EISSN

1549-9642

Publication Date

July 2016

Volume

12

Issue

5

Start / End Page

1279 / 1290

Location

United States

Related Subject Headings

  • Tissue Distribution
  • Polymers
  • Nanoscience & Nanotechnology
  • Nanoparticles
  • Mitomycin
  • Mice
  • Lipids
  • Humans
  • Drug Synergism
  • Drug Resistance, Neoplasm