Mitochondria-targeting "Nanoheater" for enhanced photothermal/chemo-therapy

Biomaterials. 2017 Feb:117:92-104. doi: 10.1016/j.biomaterials.2016.11.056. Epub 2016 Dec 2.

Abstract

In this work, mitochondria-targeting gold nanostar (AuNS) and anticarcinogen DOX were co-encapsulated in hyaluronic acid (HA) protective shell for tumor-targeting synergistic photothermal/chemo-therapy. Cationic peptide R8 and mitochondria-targeting pro-apoptotic peptide TPP-KLA were co-decorated on AuNS to form AuNS-pep via Au-S bonds. Then, electronegative HA was further coated on the surface via electrostatic interaction for cancer cell targeting. During the coating process, DOX was also introduced via electrostatic interaction to obtain a versatile nanoplatform AuNS-pep/DOX@HA. It was found that the nanoplatform could be internalized into tumor cells via CD44 receptor-mediated recognition. Followed digestion by hyaluronidase (HAase), the therapeutic nanoplatform was able to release DOX for chemotherapy and mitochondria-targeting nanoheater AuNS-pep for near infrared (NIR) light triggered subcellular photothermal therapy (PTT). This tumor-targeting nanoplatform AuNS-pep/DOX@HA displayed prominent non-resistant or resistant tumor inhibition both in vitro and in vivo.

Keywords: Combination therapy; Gold nanostar; Mitochondria-targeting; Photothermal therapy; Pro-apoptotic peptide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / administration & dosage
  • Antibiotics, Antineoplastic / chemistry
  • Cell Line, Tumor
  • Combined Modality Therapy / methods
  • Doxorubicin / administration & dosage*
  • Doxorubicin / chemistry
  • Drug Therapy / methods
  • Female
  • Gold / administration & dosage
  • Gold / chemistry
  • Metal Nanoparticles / administration & dosage*
  • Metal Nanoparticles / chemistry
  • Metal Nanoparticles / ultrastructure
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Mitochondria / drug effects*
  • Nanocapsules / administration & dosage*
  • Nanocapsules / chemistry
  • Neoplasms, Experimental / drug therapy*
  • Neoplasms, Experimental / pathology
  • Particle Size
  • Photochemotherapy / methods*
  • Photosensitizing Agents / administration & dosage*
  • Treatment Outcome

Substances

  • Antibiotics, Antineoplastic
  • Nanocapsules
  • Photosensitizing Agents
  • Gold
  • Doxorubicin