Mild photothermal therapy/photodynamic therapy/chemotherapy of breast cancer by Lyp-1 modified Docetaxel/IR820 Co-loaded micelles

Biomaterials. 2016 Nov:106:119-33. doi: 10.1016/j.biomaterials.2016.08.016. Epub 2016 Aug 12.

Abstract

Patients suffering from cancer have benefited from combination therapy. Nanocarriers are the ideal candidates for combination therapy. In this study, we constructed docetaxel (DTX) loaded micellar nanomedicines co-loaded with near infrared (NIR) dye-IR820 for photothermal therapy (PTT)/photodynamic therapy (PDT)/chemotherapy of breast cancer. Lyp-1, a tumor homing peptide, was introduced into the nanosystems to construct the active targeting nanomedicine. In order to deliver IR820 to the tumor site and overcome its short lifetime in vivo, a PEI derivative-PCL-g-PEI was introduced. IR820 with negative charge was formed stable static interaction with the amine groups, meanwhile, the absorption of IR820 in the NIR region was weakened. It indicated that the nanosystem constructed in this study may provide an alternative candidate for mild PTT. By the evaluation of the photothermal conversion in vivo, we can confirm that IR820 has been successfully delivered and effectively accumulated in the tumor site. Furthermore, the tumor cells targeting and anticancer performances of this nanosystem have been studied in vitro and in vivo. The results demonstrated Lyp-1 modification has enhanced the tumor targeting delivery of DTX and IR820. By combining PTT and PDT, DTX nanomedicine efficiently inhibited the growth and metastasis of breast cancer in mice. This nanosystem is a promising candidate for combination therapy of breast cancer.

Keywords: Cancer therapy; Chemotherapy; Micelle; Photodynamic therapy; Photothermal therapy.

MeSH terms

  • Animals
  • Antineoplastic Agents
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy*
  • Combined Modality Therapy / methods
  • Docetaxel
  • Emulsions / chemistry
  • Female
  • Hyperthermia, Induced / methods
  • Indocyanine Green / administration & dosage
  • Indocyanine Green / analogs & derivatives*
  • Infrared Rays / therapeutic use
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Micelles
  • Molecular Targeted Therapy / methods
  • Nanocapsules / administration & dosage
  • Nanocapsules / chemistry*
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / pharmacokinetics*
  • Photochemotherapy / methods*
  • Photosensitizing Agents / administration & dosage
  • Phototherapy / methods
  • Taxoids / administration & dosage*
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Emulsions
  • IR 820
  • LyP-1 peptide
  • Micelles
  • Nanocapsules
  • Peptides, Cyclic
  • Photosensitizing Agents
  • Taxoids
  • Docetaxel
  • Indocyanine Green