Synthesis and Encapsulation of a New Zinc Phthalocyanine Photosensitizer into Polymeric Nanoparticles to Enhance Cell Uptake and Phototoxicity

Nahid Mehraban,Harold Freeman,Phillip Musich

doi:10.3390/app9030401

Nahid Mehraban, Harold Freeman + Show 1 more

Open Access

https://doi.org/10.3390/app9030401

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Abstract

Efforts to enhance the utility of photodynamic therapy as a non-invasive method for treating certain cancers have often involved the design of dye sensitizers with increased singlet oxygen efficiency. More recently, however, sensitizers with greater selectivity for tumor cells than surrounding tissue have been targeted. The present study provides an approach to the modification of the known photosensitizer zinc phthalocyanine (ZnPc), to enhance its solubility and delivery to cancer cells. Targeting a photosensitizer to the site of action improves the efficacy of the sensitizer in photodynamic therapy. In this work we used PLGA-b-PEG to encapsulate a new zinc phthalocyanine derivative, 2(3), 9(10), 16(17), 23(24)-tetrakis-(4’-methyl-benzyloxy) phthalocyanine zinc(II) (ZnPcBCH3), to enhance uptake into A549 cells, a human lung cancer cell line. ZnPcBCH3 exhibited the same photochemical properties as the parent compound ZnPc but gave increased solubility in organic solvents, which allowed for efficient encapsulation. In addition, the encapsulated dye showed a near 500-fold increase in phototoxicity for A549 cancer cells compared to free dye.

Highlights

Photodynamic therapy (PDT) is a noninvasive modality that can be used to treat cancers and certain oral and infectious diseases [1,2]
PDT involves the action of a photosensitizer (PS), oxygen, and light in combination to form reactive oxygen species (ROS) to kill cancer cells
The energy of the first triplet state can be transferred to the surrounding molecular oxygen (3 O2 ) to form a reactive species such as singlet oxygen (1 O2 ), and the sensitizer returns to S0

Summary

Introduction

Photodynamic therapy (PDT) is a noninvasive modality that can be used to treat cancers and certain oral and infectious diseases [1,2]. The energy of the first triplet state can be transferred to the surrounding molecular oxygen (3 O2 ) to form a reactive species such as singlet oxygen (1 O2 ), and the sensitizer returns to S0. This cycle can be repeated multiple times, depending on the photostability of the sensitizer. The minimum energy difference (∆ES0 -T1 ) needed between the two states in order for a fluorescent dye to function as a sensitizer (1 O2 producer) for PDT is 0.98 eV [5] In this regard, molecular modeling tools can be used to screen potential photosensitizers for PDT use, by calculating ∆ES0 -T1

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