Enhancing antitumor efficacy of NIR-I region zinc phthalocyanine@upconversion nanoparticle through lysosomal escape and mitochondria targeting.

Accurately visualizing the intracellular trafficking of upconversion nanoparticles (UCNPs) loaded with phthalocyanines and achieving precise photodynamic therapy (PDT) using near-infrared (NIR) laser irradiation still present challenges. In this study, a novel NIR laser-triggered upconversion luminescence (UCL) imaging-guided nanoparticle called FA@TPA-NH-ZnPc@UCNPs (FTU) was developed for PDT. FTU consisted of UCNPs, folic acid (FA), and triphenylamino-phenylaniline zinc phthalocyanine (TPA-NH-ZnPc). Notably, TPA-NH-ZnPc showcases aggregation-induced emission (AIE) characteristic and NIR absorption properties at 741 nm, synthesized initially via molybdenum-catalyzed condensation reaction. The UCL emitted by FTU enable real-time visualization of their subcellular localization and intracellular trafficking within ovarian cancer HO-8910 cells. Fluorescence images revealed that FTU managed to escape from lysosomes due to the "proton sponge" effect of TPA-NH-ZnPc. The FA ligands on the surface of FTU further directed their transport and accumulation within mitochondria. When excited by a 980 nm laser, FTU exhibited UCL and activated TPA-NH-ZnPc, consequently generating cytotoxic singlet oxygen (1O2), disrupted mitochondrial function and induced apoptosis in cancer cells, which demonstrated great potential for tumor ablation.

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

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.