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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Zhang, RX; Cai, P; Zhang, T; Chen, K; Li, J; Cheng, J; Pang, KS; Adissu, HA; Rauth, AM; Wu, XY

Published Date

  • July 2016

Published In

Volume / Issue

  • 12 / 5

Start / End Page

  • 1279 - 1290

PubMed ID

  • 26772427

Pubmed Central ID

  • 26772427

Electronic International Standard Serial Number (EISSN)

  • 1549-9642

Digital Object Identifier (DOI)

  • 10.1016/j.nano.2015.12.383

Language

  • eng

Conference Location

  • United States