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Simultaneous delivery of siRNA and paclitaxel via a "two-in-one" micelleplex promotes synergistic tumor suppression.

Publication ,  Journal Article
Sun, T-M; Du, J-Z; Yao, Y-D; Mao, C-Q; Dou, S; Huang, S-Y; Zhang, P-Z; Leong, KW; Song, E-W; Wang, J
Published in: ACS nano
February 2011

Combination of two or more therapeutic strategies with different mechanisms can cooperatively prohibit cancer development. Combination of chemotherapy and small interfering RNA (siRNA)-based therapy represents an example of this approach. Hypothesizing that the chemotherapeutic drug and the siRNA should be simultaneously delivered to the same tumoral cell to exert their synergistic effect, the development of delivery systems that can efficiently encapsulate two drugs and successfully deliver payloads to targeted sites via systemic administration has proven to be challenging. Here, we demonstrate an innovative "two-in-one" micelleplex approach based on micellar nanoparticles of a biodegradable triblock copolymer poly(ethylene glycol)-b-poly(ε-caprolactone)-b-poly(2-aminoethyl ethylene phosphate) to systemically deliver the siRNA and chemotherapeutic drug. We show clear evidence that the micelleplex is capable of delivering siRNA and paclitaxel simultaneously to the same tumoral cells both in vitro and in vivo. We further demonstrate that systemic administration of the micelleplex carrying polo-like kinase 1 (Plk1) specific siRNA and paclitaxel can induce a synergistic tumor suppression effect in the MDA-MB-435s xenograft murine model, requiring a thousand-fold less paclitaxel than needed for paclitaxel monotherapy delivered by the micelleplex and without activation of the innate immune response or generation of carrier-associated toxicity.

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Published In

ACS nano

DOI

EISSN

1936-086X

ISSN

1936-0851

Publication Date

February 2011

Volume

5

Issue

2

Start / End Page

1483 / 1494

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Time Factors
  • RNA, Small Interfering
  • Proto-Oncogene Proteins
  • Protein Serine-Threonine Kinases
  • Polymers
  • Polo-Like Kinase 1
  • Paclitaxel
  • Neoplasms
  • Nanoscience & Nanotechnology
 

Citation

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Sun, T.-M., Du, J.-Z., Yao, Y.-D., Mao, C.-Q., Dou, S., Huang, S.-Y., … Wang, J. (2011). Simultaneous delivery of siRNA and paclitaxel via a "two-in-one" micelleplex promotes synergistic tumor suppression. ACS Nano, 5(2), 1483–1494. https://doi.org/10.1021/nn103349h
Sun, Tian-Meng, Jin-Zhi Du, Yan-Dan Yao, Cheng-Qiong Mao, Shuang Dou, Song-Yin Huang, Pei-Zhuo Zhang, Kam W. Leong, Er-Wei Song, and Jun Wang. “Simultaneous delivery of siRNA and paclitaxel via a "two-in-one" micelleplex promotes synergistic tumor suppression.ACS Nano 5, no. 2 (February 2011): 1483–94. https://doi.org/10.1021/nn103349h.
Sun T-M, Du J-Z, Yao Y-D, Mao C-Q, Dou S, Huang S-Y, et al. Simultaneous delivery of siRNA and paclitaxel via a "two-in-one" micelleplex promotes synergistic tumor suppression. ACS nano. 2011 Feb;5(2):1483–94.
Sun, Tian-Meng, et al. “Simultaneous delivery of siRNA and paclitaxel via a "two-in-one" micelleplex promotes synergistic tumor suppression.ACS Nano, vol. 5, no. 2, Feb. 2011, pp. 1483–94. Epmc, doi:10.1021/nn103349h.
Sun T-M, Du J-Z, Yao Y-D, Mao C-Q, Dou S, Huang S-Y, Zhang P-Z, Leong KW, Song E-W, Wang J. Simultaneous delivery of siRNA and paclitaxel via a "two-in-one" micelleplex promotes synergistic tumor suppression. ACS nano. 2011 Feb;5(2):1483–1494.
Journal cover image

Published In

ACS nano

DOI

EISSN

1936-086X

ISSN

1936-0851

Publication Date

February 2011

Volume

5

Issue

2

Start / End Page

1483 / 1494

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Time Factors
  • RNA, Small Interfering
  • Proto-Oncogene Proteins
  • Protein Serine-Threonine Kinases
  • Polymers
  • Polo-Like Kinase 1
  • Paclitaxel
  • Neoplasms
  • Nanoscience & Nanotechnology