Programmed co-delivery of paclitaxel and doxorubicin boosted by camouflaging with erythrocyte membrane

Nanoscale. 2015 Mar 7;7(9):4020-30. doi: 10.1039/c4nr07027e.

Abstract

Combination chemotherapy has been proven promising for cancer treatment, but unsatisfactory therapeutic data and increased side effects slow down the development in the clinic. In this study, we develop an effective approach to co-encapsulate a hydrophilic-hydrophobic chemotherapeutic drug pair (paclitaxel and doxorubicin) into magnetic O-carboxymethyl-chitosan nanoparticles. To endow them with the ability of programmed delivery, these carriers are further camouflaged with an Arg-Gly-Asp anchored erythrocyte membrane. Compared with the traditional polyethylene glycol coating method, this biomimetic decoration strategy is demonstrated to be superior in prolonging circulation time, improving tumor accumulation, facilitating tumor uptake, and tuning intracellular fate. These outstanding properties enable the as-designed nanodevice to exhibit greater tumor growth inhibition ability and much lower side effects than the combined use of commercial formulations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Cell Line
  • Cell Survival / drug effects
  • Chitosan / analogs & derivatives
  • Chitosan / chemistry
  • Doxorubicin / administration & dosage
  • Doxorubicin / chemistry*
  • Doxorubicin / pharmacology
  • Drug Carriers / chemistry*
  • Erythrocyte Membrane / metabolism*
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Magnetic Fields
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nanoparticles / chemistry
  • Neoplasms / drug therapy
  • Neoplasms / mortality
  • Neoplasms / pathology
  • Oligopeptides / chemistry
  • Oligopeptides / metabolism*
  • Paclitaxel / administration & dosage
  • Paclitaxel / chemistry*
  • Paclitaxel / pharmacology
  • Polyethylene Glycols / chemistry
  • Survival Rate
  • Tissue Distribution

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Oligopeptides
  • carboxymethyl-chitosan
  • Polyethylene Glycols
  • arginyl-glycyl-aspartic acid
  • Doxorubicin
  • Chitosan
  • Paclitaxel