pH-sensitive nanomicelles for controlled and efficient drug delivery to human colorectal carcinoma LoVo cells

PLoS One. 2014 Jun 25;9(6):e100732. doi: 10.1371/journal.pone.0100732. eCollection 2014.

Abstract

Background: The triblock copolymers PEG-P(Asp-DIP)-P(Lys-Ca) (PEALCa) of polyethylene glycol (PEG), poly(N-(N',N'-diisopropylaminoethyl) aspartamide) (P(Asp-DIP)), and poly (lysine-cholic acid) (P(Lys-Ca)) were synthesized as a pH-sensitive drug delivery system. In neutral aqueous environment such as physiological environment, PEALCa can self-assemble into stable vesicles with a size around 50-60 nm, avoid uptake by the reticuloendothelial system (RES), and encase the drug in the core. However, the PEALCa micelles disassemble and release drug rapidly in acidic environment that resembles lysosomal compartments.

Methodology/principal findings: The anticancer drug Paclitaxel (PTX) and hydrophilic superparamagnetic iron oxide (SPIO) were encapsulated inside the core of the PEALCa micelles and used for potential cancer therapy. Drug release study revealed that PTX in the micelles was released faster at pH 5.0 than at pH 7.4. Cell culture studies showed that the PTX-SPIO-PEALCa micelle was effectively internalized by human colon carcinoma cell line (LoVo cells), and PTX could be embedded inside lysosomal compartments. Moreover, the human colorectal carcinoma (CRC) LoVo cells delivery effect was verified in vivo by magnetic resonance imaging (MRI) and histology analysis. Consequently effective suppression of CRC LoVo cell growth was evaluated.

Conclusions/significance: These results indicated that the PTX-SPION-loaded pH-sensitive micelles were a promising MRI-visible drug release system for colorectal cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic
  • Colorectal Neoplasms / pathology*
  • Drug Carriers / chemistry*
  • Drug Carriers / toxicity
  • Ferric Compounds / chemistry
  • Humans
  • Intracellular Space / metabolism
  • Materials Testing
  • Mice
  • Micelles*
  • Nanoparticles / chemistry*
  • Paclitaxel / chemistry
  • Paclitaxel / metabolism
  • Paclitaxel / pharmacology
  • Particle Size
  • Polymers / chemistry*

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Ferric Compounds
  • Micelles
  • Polymers
  • ferric oxide
  • Paclitaxel

Grants and funding

This work was supported by: 1. National Natural Science Foundation of China (81000626); 2. Zhujiang Scientific and Technological New Star Foundation (2012J2200084); 3. Fundamental Research Funds for the Central Universities (10ykpy11); 4. Natural Science Foundation of Guangdong Province (S2013010016004). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.