Multifaceted NIR-responsive polymer-peptide-enveloped drug-loaded copper sulfide nanoplatform for chemo-phototherapy against highly tumorigenic prostate cancer

Nanomedicine. 2019 Oct:21:102042. doi: 10.1016/j.nano.2019.102042. Epub 2019 Jun 24.

Abstract

Targeted, biocompatible, and synergistic "all in one" systems should be designed to combat the heterogeneity of cancer. In this study, we constructed a dual function nanosystem, copper sulfide nanoplatform loaded with the chemotherapeutic drug docetaxel wrapped by a conjugated polymer-peptide for targeted chemo-phototherapy. The nanoconstruct has been successfully designed with a size of 186.1 ± 5.2 nm, a polydispersity index of 0.18 ± 0.01, and zeta potential of -16.4 ± 0.1 mV. The enhanced uptake and near-infrared-responsive behavior of the nanosystem resulted in efficient drug release, photothermal ablation, effective cytotoxic activity, and potentiated reactive oxygen species generation. The induction of apoptotic markers, enhanced accumulation in the tumor site, and maximum tumor growth inhibition were seen during in vivo studies compared to non-targeted nanoformulations and free drug. Cumulatively, our results indicate that, with low systemic toxicity and better biocompatibility, this nanoconstruct could provide a promising strategy for treating prostate cancer.

Keywords: Copper sulfide; Docetaxel; Lanreotide; Nanoconstruct; Somatostatin receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / radiation effects
  • Cell Proliferation / drug effects
  • Copper / chemistry
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacology*
  • Drug Delivery Systems*
  • Drug Liberation / radiation effects
  • Humans
  • Hyperthermia, Induced
  • Male
  • Nanoparticles / chemistry
  • Peptides / chemistry
  • Peptides / pharmacology
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / pharmacology
  • Phototherapy
  • Polymers / chemistry
  • Polymers / pharmacology*
  • Polymers / radiation effects
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / pathology
  • Reactive Oxygen Species / chemistry
  • Receptors, Somatostatin / genetics
  • Somatostatin / analogs & derivatives
  • Somatostatin / chemistry
  • Somatostatin / pharmacology
  • Sulfides / chemistry

Substances

  • Antineoplastic Agents
  • Peptides
  • Peptides, Cyclic
  • Polymers
  • Reactive Oxygen Species
  • Receptors, Somatostatin
  • Sulfides
  • lanreotide
  • Somatostatin
  • Copper
  • Doxorubicin