A novel nanoparticle drug delivery system based on PEGylated hemoglobin for cancer therapy

Drug Deliv. 2019 Dec;26(1):717-723. doi: 10.1080/10717544.2019.1639846.

Abstract

Proteins such as albumin, gelatin, casein, transferrin, and collagen are widely used as drug delivery systems. However, only albumin-based paclitaxel (PTX) formulation Abraxane® (PTX-albumin NPs prepared by nab-technology) has been successfully developed for treating metastatic breast cancer clinically due to abundant materials, simple industrial scale-up process, and well tumor-targeting ability. Hemoglobin (Hb) is another protein used for drug delivery with similar advantages. In this study, we successfully synthesized PEG-Hb nanoparticles loading with PTX based on previously well-established acid-denatured method. PEG-Hb-PTX NPs showed enhanced cellular uptake and great cellular inhibition ability in vitro. Moreover, our animal study showed that PEGylated NPs greatly accumulated in tumor tissues and exhibited excellent anticancer activity in vivo. We found that PEG-Hb-PTX NPs possess a better in vivo antitumor effect than the commercially available Taxol® formulation. We believe that PEG-Hb has great potential as an efficient drug delivery system for further clinic study.

Keywords: PEGylated hemoglobin; antitumor study; drug delivery; nanoparticles.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Drug Delivery Systems
  • Female
  • Hemoglobins / chemistry*
  • Humans
  • MCF-7 Cells
  • Mammary Neoplasms, Experimental / drug therapy*
  • Mice
  • Mice, Inbred ICR
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • Nanoparticles / ultrastructure
  • Optical Imaging
  • Paclitaxel / administration & dosage*
  • Paclitaxel / chemistry
  • Paclitaxel / pharmacology
  • Paclitaxel / therapeutic use
  • Polyethylene Glycols / chemistry*
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents, Phytogenic
  • Hemoglobins
  • PEG-hemoglobin
  • Polyethylene Glycols
  • Paclitaxel

Grants and funding

This work was supported by the China Postdoctoral Science Foundation (No. 2016M601923) and by the China National Science Foundation (No. 31671026). Dr Tianqing Liu is supported by the National Health and Medical Research Council (NHMRC) Early Career Fellowship (Grant No. 1112258).