Polymeric Bis(dipyrrinato) Zinc(II) Nanoparticles as Selective Imaging Probes for Lysosomes of Cancer Cells

Abstract

Fluorescence imaging is a powerful tool in biomedical research. It has been frequently used to uncover or better understand physiological mechanisms in disease-related processes such as cancer. The majority of chromophores used for imaging are based on a 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) scaffold. However, their applications are limited due to their poor water solubility as well as poor cancer cell selectivity. To circumvent these drawbacks, we present herein the use of bis(dipyrrinato)zinc(II) complexes. As this class of compounds is associated with a quenching effect of the excited state in water, the lead compound of this study (3) was encapsulated in a polymer matrix with biotin as a targeting moiety (3-NP). This encapsulation improved the water solubility, overcame the quenching effects in water, as well as allowed selective accumulation in the lysosomes with a bright fluorescence signal in monolayer cells as well as 3D multicellular tumor spheroids (MCTS). As a benefit from the biotin targeting moiety, the nanoparticles were majorly taken up by the sodium dependent multivitamin transporter (SMVT) which is overexpressed in various cancers cells and selectively accumulated in cancerous cells over noncancerous cells.

Probing biotin receptors in cancer cells with rationally designed fluorogenic squaraine dimers

“…Alternatively, recent efforts resulted in development of hybrid nanoprobes to distinguish SMVT in cancer cells and 3D spheroids. [15][16][17][18] There is a particular demand in development of probes operating in far-red and near-infrared (NIR) region to image deeper in the tissues and potentially in vivo. [19][20][21][22] A number of concepts to generate uorogenic response to target-binding was developed in the last decade.…”

Metal dipyrrin complexes as potential photosensitizers for photodynamic therapy

“…Despite much progress in the tuning of the photophysical properties of these complexes, the corresponding BODIPY complexes remain the best of the class. [19][20][21][22][23][24] Next to applications as fluorescent probes, dipyrrin complexes and especially BODIPY complexes have also recently received attention for their utilisation as photosensitizers (PSs) for photodynamic therapy (PDT) for the treatment of bacterial, fungal or viral infections as well as various types of cancer (e.g., lung, bladder, oesophageal, and brain cancer). [25][26][27][28][29][30] During a PDT treatment, a PS is injected, either locally or systemically.…”

Polymeric Encapsulation of a Ruthenium Polypyridine Complex for Tumor Targeted 1- and 2-Photon Photodynamic Therapy

“…Worthy of note, homoleptic zinc(II) dipyrromethene complexes and large organic aromatic systems, which were encapsulated with the same polymer matrix but with different terminal group were also found mostly in the lysosomes. [108][109][110] Following this, the cellular uptake mechanism of NP in A549 cells was investigated. As there is a higher demand for biotin in rapidly growing cells than in healthy cells, biotin and its conjugates are rapdily internalized by the sodium multivitamin transporter (SMVT), which is overexpressed in a variety of cancers.…”