Multifunctional Nanoparticles of Biodegradable Copolymer Blend for Cancer Diagnosis and Treatment

Abstract

Aims: A multifunctional nanoparticle (NP) system is developed to provide a sustained, controlled and targeted co-delivery of quantum dots (QDs) as a model imaging agent and docetaxel as a model anticancer drug. The NPs are made of a polymeric blend of poly(lactic-co-glycolic acid), which forms a biodegradable NP matrix, and the novel copolymer D-α-tocopheryl polyethylene glycol 1000 succinate-COOH, which facilitates ligand conjugation on the NP surface. Materials & methods: The NPs were prepared by nanoprecipitation and characterized for their size and size distribution, surface morphology, surface charge, QD/drug encapsulation and loading efficiency, and in vitro drug release profile. The targeting effects of such NPs were evaluated both quantitatively and qualitatively through the cellular uptake of the QDs as well as the cytotoxicity of the drug using MCF-7 cells, which overexpress folate receptors and NIH 3T3 cells, which have no folate receptors overexpression. Results & conclusions: NPs with folate conjugated on their surface achieved much higher cellular uptake than those with no folate conjugation in MCF-7 cells while no significant targeting effect could be observed for NIH 3T3 cells. The drug formulated in the folate-conjugated NPs were more efficious compared with NPs with no folate conjugation as well as the current clinical formulation Taxotere^®.

Keywords::

• cancer nanotechnology
• drug delivery
• molecular imaging
• nanobiotechnology
• quantum dots
• Taxotere ^®

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Financial & competing interests disclosure

This research was supported by NUS Grant R279–000–226–112 (from FRC, 2007–2009) and R-263–000–432–646 (from NanoCore, 2009–2010), National University of Singapore (Si-Shen Feng). Jie Pan and Yutao Liu are grateful to the National University of Singapore for their PhD scholarship. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This research was supported by NUS Grant R279–000–226–112 (from FRC, 2007–2009) and R-263–000–432–646 (from NanoCore, 2009–2010), National University of Singapore (Si-Shen Feng). Jie Pan and Yutao Liu are grateful to the National University of Singapore for their PhD scholarship. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.