"Triple-punch" strategy for triple negative breast cancer therapy with minimized drug dosage and improved antitumor efficacy

ACS Nano. 2015 Feb 24;9(2):1367-78. doi: 10.1021/nn505729m. Epub 2015 Jan 26.

Abstract

Effective therapeutics against triple negative breast cancer (TNBC), which has no standard-of-care therapy, needs to be developed urgently. Here we demonstrated a strategy of integrating indocyanine green (ICG), paclitaxel (PTX), and survivin siRNA into one thermosensitive poly(2-(2-methoxyethoxy)ethyl methacrylate-co-oligo(ethylene glycol) methacrylate)-co-2-(dimethylamino)ethyl methacrylate-b-poly(D,L-lactide-co-glycolide) (P (MEO2MA-co-OEGMA-co-DMAEMA)-b-PLGA) nanoparticle (NP-IPS) for triple-punch strategy against TNBC. The NP-IPS significantly enhanced the stability of ICG. Controlled release of the PTX in tumor regions was triggered by the hyperthermia produced by laser irradiated ICG. The NP-IPS exhibited remarkable antitumor efficacy (almost complete ablation of the tumor xenografts) due to the combinational effects of chemotherapy, photothermal therapy, and gene therapy with low drug dose (ICG, 0.32 μmol/kg; PTX, 0.54 μmol/kg; siRNA, 1.5 mg/kg) and minimal side effects. Taken together, our current study demonstrates a nanoplatform for triple-therapy, which reveals a promising strategy for TNBC treatment.

Keywords: combination antitumor therapy; thermoresponsive; triple negative breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Cell Line, Tumor
  • Drug Carriers / chemistry*
  • Drug Carriers / metabolism
  • Drug Carriers / pharmacokinetics
  • Endocytosis
  • Female
  • Humans
  • Indocyanine Green / chemistry
  • Inhibitor of Apoptosis Proteins / deficiency
  • Inhibitor of Apoptosis Proteins / genetics
  • Intracellular Space / metabolism
  • Lactic Acid / chemistry
  • Methacrylates / chemistry
  • Mice
  • Mice, Inbred BALB C
  • Nanomedicine / methods*
  • Nanoparticles / chemistry
  • Paclitaxel / chemistry
  • Paclitaxel / pharmacology
  • Paclitaxel / therapeutic use
  • Polyethylene Glycols / chemistry
  • Polyglycolic Acid / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • RNA, Small Interfering / chemistry
  • RNA, Small Interfering / genetics
  • Survivin
  • Triple Negative Breast Neoplasms / drug therapy*
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / pathology

Substances

  • Antineoplastic Agents
  • BIRC5 protein, human
  • Drug Carriers
  • Inhibitor of Apoptosis Proteins
  • Methacrylates
  • RNA, Small Interfering
  • Survivin
  • poly(2-(2-methoxyethoxy)ethyl methacrylate-co-oligo(ethylene glycol) methacrylate)
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Polyethylene Glycols
  • Indocyanine Green
  • 2-(dimethylamino)ethyl methacrylate
  • Paclitaxel