Multifunctional lipid-coated calcium phosphate nanoplatforms for complete inhibition of large triple negative breast cancer via targeted combined therapy

Biomaterials. 2019 Sep:216:119232. doi: 10.1016/j.biomaterials.2019.119232. Epub 2019 May 31.

Abstract

Combined and targeted therapy have been extensively employed to achieve more effective elimination of tumor tissues. In this study, biocompatible multifunctional lipid-coated calcium phosphate nanoparticles (LCP NPs) were designed and constructed as an efficient targeted delivery system for combined gene/photothermal therapy to inhibit growth of the triple negative breast tumor (MDA-MB-468) in vitro and in vivo. LCP NPs were functionalized with a bispecific antibody (BsAb) via non-covalent bond specific for methoxy group of PEG (mPEG) on the particle surface. This BsAb is also able to target epidermal growth factor receptor (EGFR) expressed on MDA-MB-468 cells. Such LCP-BsAb NPs loaded with Cell Death (CD)-siRNA and indocyanine green (ICG) were efficiently taken up by MDA-MB-468 cells, significantly inducing cell apoptosis and synergistically suppressing cell proliferation upon irradiation of 808 nm near-infrared laser. These targeted multifunctional LCP NPs more efficiently accumulated in the tumor tissue. The combined RNAi (CD-siRNA) and photothermal (ICG) therapy using the targeted LCP NPs nearly eliminated both small tumors (∼100 mm3) and large tumors (∼500 mm3) in the mouse model. Thus, the well-devised multifunctional LCP NPs are one of the most promising delivery systems for combined and targeted cancer therapy.

Keywords: Bispecific target delivery; Large breast tumor model; Lipid-coated calcium phosphate nanoparticles; Photothermal therapy; RNAi therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Phosphates / chemistry*
  • Cell Line, Tumor
  • Coloring Agents / administration & dosage*
  • Coloring Agents / therapeutic use
  • Drug Carriers / chemistry*
  • Drug Delivery Systems
  • Female
  • Genetic Therapy
  • Humans
  • Hyperthermia, Induced
  • Indocyanine Green / administration & dosage*
  • Indocyanine Green / therapeutic use
  • Lipids / chemistry*
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles / chemistry
  • RNAi Therapeutics
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / therapy*

Substances

  • Calcium Phosphates
  • Coloring Agents
  • Drug Carriers
  • Lipids
  • calcium phosphate
  • Indocyanine Green