Fluorescent Phthalocyanine-Encapsulated Bovine Serum Albumin Nanoparticles: Their Deployment as Therapeutic Agents in the NIR Region.

Raluca Borlan,Mihaela Silion,Monica Focsan,Gabriel Marc,Simion Astilean,Luiza Gaina,Andreea Campu,Dana Maniu,Daria Stoia,Maria Perde-Schrepler

doi:10.3390/molecules26154679

Abstract

In recent times, researchers have aimed for new strategies to combat cancer by the implementation of nanotechnologies in biomedical applications. This work focuses on developing protein-based nanoparticles loaded with a newly synthesized NIR emitting and absorbing phthalocyanine dye, with photodynamic and photothermal properties. More precisely, we synthesized highly reproducible bovine serum albumin-based nanoparticles (75% particle yield) through a two-step protocol and successfully encapsulated the NIR active photosensitizer agent, achieving a good loading efficiency of 91%. Making use of molecular docking simulations, we confirm that the NIR photosensitizer is well protected within the nanoparticles, docked in site I of the albumin molecule. Encouraging results were obtained for our nanoparticles towards biomedical use, thanks to their negatively charged surface (−13.6 ± 0.5 mV) and hydrodynamic diameter (25.06 ± 0.62 nm), favorable for benefitting from the enhanced permeability and retention effect; moreover, the MTT viability assay upholds the good biocompatibility of our NIR active nanoparticles. Finally, upon irradiation with an NIR 785 nm laser, the dual phototherapeutic effect of our NIR fluorescent nanoparticles was highlighted by their excellent light-to-heat conversion performance (photothermal conversion efficiency 20%) and good photothermal and size stability, supporting their further implementation as fluorescent therapeutic agents in biomedical applications.

Highlights

After heart disease, cancer is the second most frequent cause of death around the world, with over 4.5 million new cases and over 2 million deaths in 2018 [1]
Phthalocyanine synthesis implies a macrocyclization reaction, using starting materials which fall in two different categories: the first one which needs an extra source of nitrogen and the second one which does not necessarily need an external nitrogen source and a metal halide or salt for metalated phthalocyanine, respectively
The photothermal assay performed in the presence of the BSA&phthaloNH2 NPs was a success, with an increase of 10 ◦C after only 15 min of irradiation with the 785 nm NIR laser, compared to the free phthaloNH2, which increases its temperature by 11 ◦C after 9 min of irradiation but reaches a saturation point, and by the 15th minute of irradiation, its temperature is decreased by 2 ◦C

Summary

Introduction

Cancer is the second most frequent cause of death around the world, with over 4.5 million new cases and over 2 million deaths in 2018 [1]. An up-and-coming cancer treatment method is photodynamic therapy (PDT) For this therapy to work, three elements, namely a photosensitizer (PS) agent, PS specific excitation wavelength light, and intracellular oxygen, are indispensable. If we combine these three elements, they produce photochemical reactions that lead to the generation of cytotoxic reactive oxygen species, predominantly singlet oxygen (1O2). This reactive oxygen species can trigger the patient’s immune system, can close the vasculature around the tumor, and, most importantly, can cause immediate cancer cell death [5,6].

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