Platelet membrane-cloaked paclitaxel-nanocrystals augment postoperative chemotherapeutical efficacy

J Control Release. 2020 Aug 10:324:341-353. doi: 10.1016/j.jconrel.2020.05.016. Epub 2020 May 15.

Abstract

Chemotherapy post cancer surgery has important clinical significance for reducing the chance of recurrent-metastasis. However, postoperative chemotherapy efficacy is hampered by poor targeting capability and dose-limiting toxicity of chemo-drugs. Herein, we report a bio-mimetic platelet membrane-cloaked paclitaxel nanocrystal system (PPNCs), which consists of spherical paclitaxel nanocrystals (PNCs) as a high-dose drug core, polyethylene glycol-conjugated paclitaxel (PEG-PTX) as an amphiphilic molecule to adjust the surface hydrophilicity of PNCs and the shell of platelet membrane that can target surgical coagulation site. The in vitro characterization of PPNCs exhibited uniform particle size distribution, high drug loading, and good stability, which are crucial for effective drug delivery. At cell levels, PPNCs showed greater cellular uptake and higher cytotoxicity in 4T1 breast cancer cells than bare PNCs. In vivo, the nanoparticles could deliver high-dose chemo-drugs and target the coagulation site caused by surgery or vascular disrupting agents, resulting in enhanced anti-tumor efficacy and reduced systemic toxicities. In general, the PPNCs system can be served as a promising and efficient drug delivery system for postoperative chemotherapy.

Keywords: Bio-mimetic nanocarrier; Breast cancer; Drug nanocrystals; Postoperative chemotherapy; Tumor targeting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents*
  • Cell Line, Tumor
  • Nanoparticles*
  • Paclitaxel
  • Particle Size
  • Polyethylene Glycols

Substances

  • Antineoplastic Agents
  • Polyethylene Glycols
  • Paclitaxel