A piperazine-substituted phthalocyanine with rapid cellular uptake and dual organelle-targeting for in vitro photodynamic therapy

Haijian Wu; Guowei Liu; Kuizhi Chen; Tiantian Zhang; Qiuhao Ye; Jianling Chen; Yiru Peng

doi:10.1016/j.pdpdt.2023.103818

A piperazine-substituted phthalocyanine with rapid cellular uptake and dual organelle-targeting for in vitro photodynamic therapy

Photodiagnosis Photodyn Ther. 2023 Dec:44:103818. doi: 10.1016/j.pdpdt.2023.103818. Epub 2023 Oct 1.

Authors

Haijian Wu¹, Guowei Liu¹, Kuizhi Chen¹, Tiantian Zhang¹, Qiuhao Ye¹, Jianling Chen², Yiru Peng³

Affiliations

¹ Fujian Provincial Key Laboratory of Advanced Materials Oriented Chemical Engineering, College of Chemistry and Materials, Fujian Normal University, Fuzhou, China.
² Key Laboratory of Optoelectronic Science and Technology for Medicine of Ministry of Education, Provincial Key Laboratory for Photonics Technology, Institute of Laser and Optoelectronics Technology, Fujian Normal University, Fuzhou, China. Electronic address: jlchen@fjnu.edu.cn.
³ Fujian Provincial Key Laboratory of Advanced Materials Oriented Chemical Engineering, College of Chemistry and Materials, Fujian Normal University, Fuzhou, China. Electronic address: yirupeng@fjnu.edu.cn.

PMID: 37788794
DOI: 10.1016/j.pdpdt.2023.103818

Abstract

The rational design of photosensitizers with rapid cellular uptake and dual-organelle targeting ability is essential for enhancing the efficacy of photodynamic therapy (PDT). However, achieving this goal is a great challenge. In this paper, a novel axial piperazine substituted (PIP) silicon phthalocyanine (PIP-SiPc) has been synthesized. The PIP substitution significantly improved the cellular uptake of PIP-SiPc in MCF-7 breast cancer cells, as demonstrated by two-photon fluorescence imaging combined with fluorescence correlation spectroscopy. Additionally, PIP-SiPc was able to target both mitochondria and lysosomes simultaneously. Notably, PIP-SiPc exhibited remarkable singlet oxygen generation ability, leading to apoptosis in cancer cells upon irradiation, with an IC₅₀ value of only 0.2 µM. These findings highlight the effectiveness of PIP-SiPc as a multifunctional photosensitizer for PDT.

Keywords: Organelle targeting; Photodynamic therapy; Photosensisitizer; Phthalocyanine; Piperazine; Rapid cellular uptake.

MeSH terms

Humans
Isoindoles*
Mitochondria
Nicotinic Acids*
Photochemotherapy* / methods
Photosensitizing Agents* / chemistry
Photosensitizing Agents* / pharmacology
Piperazines / pharmacology
Succinimides*

Substances

Photosensitizing Agents
phthalocyanine
N-succinimidyl-5-iodo-3-pyridinecarboxylic acid
Piperazines
Nicotinic Acids
Succinimides
Isoindoles