[Paper Review] Drug delivery with carbon nanotubes for in vivo cancer treatment

Zhuang Liu, Kai Chen+5 more|PubMed|Aug 14, 2008

Carbon Nanotubes in Composites3 references2,331 citations

TL;DR

The paper demonstrates in vivo delivery of a paclitaxel–carbon nanotube conjugate (SWNT-PTX) that enhances tumor suppression in mice compared to Taxol, with prolonged circulation and increased tumor uptake via EPR, and with excretion via biliary pathways and minimal normal organ toxicity.

ABSTRACT

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.

Motivation & Objective

• Demonstrate in vivo tumor targeting and suppression using chemically functionalized single-walled carbon nanotubes (SWNTs).
• Show that conjugating paclitaxel to SWNTs increases water solubility and enables effective tumor delivery.
• Assess pharmacokinetics, tumor uptake, excretion pathway, and systemic toxicity of SWNT-PTX in a murine model.

Proposed method

• Conjugate paclitaxel to branched polyethylene glycol chains on SWNTs via a cleavable ester bond to form SWNT-PTX.
• Evaluate tumor suppression in a murine 4T1 breast-cancer model and compare efficacy to clinical Taxol.
• Assess blood circulation duration and tumor PTX uptake to infer delivery efficiency, likely via enhanced permeability and retention (EPR).
• Investigate release of drug molecules in the reticuloendothelial system and excretion via the biliary pathway.
• Examine potential toxicity to normal organs to determine biocompatibility.

Experimental results

Research questions

• RQ1 Can SWNTs deliver paclitaxel effectively to tumors in vivo?
• RQ2 Does SWNT-PTX provide higher tumor uptake and greater tumor suppression than Taxol in a mouse breast cancer model?
• RQ3 What are the pharmacokinetic properties and excretion pathways for SWNT-PTX, and are there observable toxic effects on normal organs?

Key findings

• SWNT-PTX shows higher efficacy in suppressing tumor growth than Taxol in a mouse breast cancer model.
• SWNT delivery yields prolonged blood circulation and higher tumor PTX uptake, consistent with EPR-based delivery.
• Drug molecules carried into the reticuloendothelial system are released from SWNTs and excreted via the biliary pathway.
• No obvious toxic effects to normal organs were observed in the study.