Sharp pH-sensitive amphiphilic polypeptide macrophotosensitizer for near infrared imaging-guided photodynamic therapy

Pan Yuan; Zheng Ruan; Tuanwei Li; Youliang Tian; Quan Cheng; Lifeng Yan

doi:10.1016/j.nano.2018.09.017

Sharp pH-sensitive amphiphilic polypeptide macrophotosensitizer for near infrared imaging-guided photodynamic therapy

Nanomedicine. 2019 Jan;15(1):198-207. doi: 10.1016/j.nano.2018.09.017. Epub 2018 Oct 11.

Authors

Pan Yuan¹, Zheng Ruan¹, Tuanwei Li¹, Youliang Tian¹, Quan Cheng¹, Lifeng Yan²

Affiliations

¹ CAS Key Laboratory of Soft Matter Chemistry, Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, PR China; Department of Chemical Physics, iCHEM, University of Science and Technology of China, Hefei, PR China.
² CAS Key Laboratory of Soft Matter Chemistry, Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, PR China; Department of Chemical Physics, iCHEM, University of Science and Technology of China, Hefei, PR China. Electronic address: lfyan@ustc.edu.cn.

PMID: 30316904
DOI: 10.1016/j.nano.2018.09.017

Abstract

Tumor environmental sensitive polypeptide integrated photosensitizer is a platform for imaging-guided photodynamic therapy (PDT). However, the photosensitizer leakage during blood circulation, poor accumulation in tumor tissue and inferior quantum yield of singlet oxygen are still challenges. Herein, NHS-active boron-dipyrromethene derivative with bromine substituted NHS-BODIPY-Br₂ was first synthesized, which possessed high singlet oxygen generation efficiency and near infrared (NIR) fluorescence, and then it was conjugated to a sharp pH (6.36) sensitive polypeptide to achieve a macrophotosensitizer for NIR imaging-guided PDT. In vitro study showed that the macrophotosensitizer nanoparticles exhibited good cellular uptake and ability to kill cancer cells. Once accumulating in the tumor tissues, the nanoparticles can be demicellized by tumor acidity to promote cellular uptake, which could enlarge fluorescence signal intensity and enhance in vivo PDT therapeutic effect upon NIR laser irradiation. It provides a strategy to design photosensitizer conjugated tumor acidity sensitive polypeptide for NIR imaging-guided photodynamic therapy.

Keywords: Imaging-guided; Macro-photosensitizer; Near infrared (NIR); Photodynamic therapy (PDT); Polypeptide.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis
Boron Compounds / chemistry
Breast Neoplasms / pathology
Breast Neoplasms / therapy*
Carcinoma, Hepatocellular / pathology
Carcinoma, Hepatocellular / therapy*
Cell Proliferation
Female
Humans
Hydrogen-Ion Concentration
Infrared Rays*
Liver Neoplasms / pathology
Liver Neoplasms / therapy*
Mice
Mice, Inbred BALB C
Mice, Nude
Nanoparticles / administration & dosage
Nanoparticles / chemistry
Peptide Fragments / administration & dosage*
Photochemotherapy*
Radiotherapy, Image-Guided*
Singlet Oxygen
Tumor Cells, Cultured
Xenograft Model Antitumor Assays

Substances

4,4-difluoro-4-bora-3a,4a-diaza-s-indacene
Boron Compounds
Peptide Fragments
Singlet Oxygen