Drug delivery with carbon nanotubes for in vivo cancer treatment

Доставка лекарственных препаратов с помощью углеродных нанотрубок для лечения рака in vivo
Xiaohong Chen, Zhuang Liu, Hongjie Dai, Kai Chen, Corrine R. Davis, Sarah C. Sherlock, Qizhen Cao, Chen, Xiaoyuan
2008-08-14

4T1 breast cancer modelenhanced permeability and retentionpaclitaxel deliverysingle-walled carbon nanotubestumor-targeted drug delivery
Chemically functionalized single-walled carbon nanotubes (SWNT) have shown promise in tumor-targeted accumulation in mice and exhibit biocompatibility, excretion, and little toxicity. Here, we show in vivo SWNT drug delivery for tumor suppression in mice. We conjugate paclitaxel (PTX), a widely used cancer chemotherapy drug, to branched polyethylene glycol chains on SWNTs via a cleavable ester bond to obtain a water-soluble SWNT-PTX conjugate. SWNT-PTX affords higher efficacy in suppressing tumor growth than clinical Taxol in a murine 4T1 breast cancer model, owing to prolonged blood circulation and 10-fold higher tumor PTX uptake by SWNT delivery likely through enhanced permeability and retention. Drug molecules carried into the reticuloendothelial system are released from SWNTs and excreted via biliary pathway without causing obvious toxic effects to normal organs. Thus, nanotube drug delivery is promising for high treatment efficacy and minimum side effects for future cancer therapy with low drug doses.
1
A water-soluble SWNT–PTX conjugate was created by attaching paclitaxel to branched PEG chains through a cleavable ester bond.
2
Chemically functionalized single-walled carbon nanotubes delivered paclitaxel in vivo and suppressed tumors in mice.
3
Paclitaxel released within the reticuloendothelial system was excreted through the biliary pathway without obvious toxicity to normal organs.
4
Prolonged blood circulation enabled approximately 10-fold higher tumor paclitaxel uptake, likely through the enhanced permeability and retention effect.
5
SWNT–PTX showed greater tumor-growth suppression than clinical Taxol in a murine 4T1 breast cancer model.

Chemically functionalized single-walled carbon nanotube–paclitaxel conjugates for in vivo delivery in mice with 4T1 breast tumors

Tumor-targeted paclitaxel delivery, tumor-growth suppression, biodistribution, excretion, efficacy, and toxicity of the SWNT conjugates compared with clinical Taxol

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2008-08-14
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Authors
Xiaohong Chen
Zhuang Liu
Hongjie Dai
Kai Chen
Corrine R. Davis
Sarah C. Sherlock
Qizhen Cao
Chen, Xiaoyuan
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