Erythrocyte Membrane-Camouflaged IR780 and DTX Coloading Polymeric Nanoparticles for Imaging-Guided Cancer Photo-Chemo Combination Therapy

Mol Pharm. 2019 Jul 1;16(7):3208-3220. doi: 10.1021/acs.molpharmaceut.9b00413. Epub 2019 Jun 11.

Abstract

Conventional systemic chemotherapy leads to poor therapeutic outcomes at moments in cancer therapy because the nontargeting anticancer drug release results in adverse effects and consequently drug resistance. The combination therapeutic strategy provides an alternative way to solve the conundrums. Herein, drug delivery systems with a rational design and tumor-targeting abilities become the ideal carriers for combinatorial therapy. IR780 iodide possesses near-infrared fluorescence intensity for fluorescence imaging (FI) and photothermal conversion for photoacoustic imaging (PAI), which also can be employed for tumor phototherapy (including photothermal therapy and photodynamic therapy). However, hydrophobicity and rapid elimination in vivo limit its biomedical applications. Furthermore, the hydrophobicity and high crystallization of IR780 result in poor drug-loading capacity and low stability. In this study, the high-pressure homogenization method was utilized for hydrophobic molecular IR780 and DTX coloading to construct IR780/DTX-PCEC nanoparticles which exhibit narrow size distribution and satisfactory drug-loading capacity. With further erythrocyte membrane [red blood cell (RBC)] camouflaging, the obtained IR780/DTX-PCEC@RBC nanoparticles present desired stability and prolonged circulation time in vivo. Additionally, the IR780/DTX-PCEC@RBC nanoparticles not only can be employed as a FI/PAI dual model imaging probe but also exhibit the property for phototherapy and chemotherapy of tumors. Based on the therapeutic outcome of combination therapy, the IR780/DTX-PCEC@RBC nanoparticles can serve as promising FI- and PAI-guided photo-chemo combination therapy agents for the future treatment of breast cancer.

Keywords: combination therapy; dual drug-loaded nanoparticles; dual model imaging; long circulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Breast Neoplasms / drug therapy*
  • Cell Survival / drug effects
  • Digitoxigenin / chemistry*
  • Digitoxigenin / pharmacokinetics
  • Drug Delivery Systems / methods*
  • Drug Liberation
  • Erythrocyte Membrane / chemistry*
  • Female
  • Humans
  • Indoles / chemistry*
  • MCF-7 Cells
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nanoparticles / chemistry*
  • Optical Imaging
  • Photochemotherapy / methods*
  • Polymers / chemistry*
  • Tissue Distribution
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • 2-(2-(2-chloro-3-((1,3-dihydro-3,3-dimethyl-1-propyl-2H-indol-2-ylidene)ethylidene)-1-cyclohexen-1-yl)ethenyl)-3,3-dimethyl-1-propylindolium
  • Indoles
  • Polymers
  • Digitoxigenin