An Engineered Nanocomplex with Photodynamic and Photothermal Synergistic Properties for Cancer Treatment.

Avi Jacob,Moshe Sinvani,Gaddi Blumrosen,Ayelet Atkins,David Zitoun,Irit Shoval,Elina Haimov,Eli Varon,Michal Natan,Shlomi Polani,Orit Shefi

doi:10.3390/ijms23042286

Avi Jacob, Moshe Sinvani + Show 9 more

Open Access

https://doi.org/10.3390/ijms23042286

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Abstract

Photodynamic therapy (PDT) and photothermal therapy (PTT) are promising therapeutic methods for cancer treatment; however, as single modality therapies, either PDT or PTT is still limited in its success rate. A dual application of both PDT and PTT, in a combined protocol, has gained immense interest. In this study, gold nanoparticles (AuNPs) were conjugated with a PDT agent, meso-tetrahydroxyphenylchlorin (mTHPC) photosensitizer, designed as nanotherapeutic agents that can activate a dual photodynamic/photothermal therapy in SH-SY5Y human neuroblastoma cells. The AuNP-mTHPC complex is biocompatible, soluble, and photostable. PDT efficiency is high because of immediate reactive oxygen species (ROS) production upon mTHPC activation by the 650-nm laser, which decreased mitochondrial membrane potential (∆ψm). Likewise, the AuNP-mTHPC complex is used as a photoabsorbing (PTA) agent for PTT, due to efficient plasmon absorption and excellent photothermal conversion characteristics of AuNPs under laser irradiation at 532 nm. Under the laser irradiation of a PDT/PTT combination, a twofold phototoxicity outcome follows, compared to PDT-only or PTT-only treatment. This indicates that PDT and PTT have synergistic effects together as a combined therapeutic method. Our study aimed at applying the AuNP-mTHPC approach as a potential treatment of cancer in the biomedical field.

Highlights

Targeted cancer therapy aims at delivering medicine to a preferential and designated site while reducing systemic dosage [1]
Our hypothesis was that the amalgamation of Photodynamic therapy (PDT) and photothermal therapy (PTT) treatment increases efficacy compared to a mono-phototherapy approach, increasing overall cell death and reducing the duration and intensity of laser irradiation needed
To overcome the clinical limitations of single-modality therapies of PDT or PTT, we introduced a PDT/PTT dual-model therapeutic agent under laser irradiation

Summary

Introduction

Targeted cancer therapy aims at delivering medicine to a preferential and designated site while reducing systemic dosage [1]. Photothermal therapy (PTT), known as optical hyperthermia, relies on photothermal agents (PTAs) with high photothermal conversion for converting light into heat to destroy cancer cells [34]. Gold nanoparticles (AuNPs) have been considered efficient photothermal agents [35,36,37,38,39,40] due to their surface plasmon resonance (SPR) effect [41], which has a high efficiency of light-to-heat conversion [42]. Our hypothesis was that the amalgamation of PDT and PTT treatment increases efficacy compared to a mono-phototherapy approach, increasing overall cell death and reducing the duration and intensity of laser irradiation needed. The 650-nm laser (PDT) activated the mTHPC conjugated drug and led to high ROS production, and the 532-nm laser (PTT) stimulated the AuNP, exerting a high photothermal conversion efficiency. Our prepared AuNP–mTHPC may be applied as an effective dual-modal phototherapeutic agent for future clinical applications

Results

Synthesis and Characterization of AuNP–mTHPC Complexes

Photothermal Imaging of AuNP–mTHPC Complexes

Internalization of AuNP–mTHPC Complexes by SH-SY5Y Cells

Phototoxicity of AuNP–mTHPC

Discussion

Materials

Cell Culture

TEM and HR-SEM

Optical Characterization of AuNP–mTHPC

Confocal and Wide-Field Microscopy

Flow Cytometry Studies