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

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.

Cytomorphological Changes in McF7-Dox Cells and Their Correlation With the Activity of the Cell Cycle Regulator P21 After Combined Exposure to Infrared Laser and Doxorubicin

“…The most studied of doxorubicin mechanism of action today is its ability to integrate into DNA base pairs, causing DNA strand breaks and inhibition of both DNA and RNA synthesis. Doxorubicin inhibits the enzyme topoisomerase II, causing DNA damage and induction of apoptosis [18][19][20][21][22]. It is likely that such effects of doxorubicin are joined by the pro-apoptotic effect of laser irradiation by modulating the metabolism of reactive oxygen species (ROS), in particular through the so-called ROS-induced ROS release, as well as by activating apoptosis regulators [23][24][25].…”

Nanotechnology-Based Diagnostic and Therapeutic Strategies for Neuroblastoma

“…Based on this, a group has synthesized a functional complex based on AuNPs covalently linked to meso-tetrahydrobenzyl chloride (mTHPC) drug molecule (AuNP-mTHPC), which enhances the pro-cell death effect of PDT in NB ( Haimov et al, 2018 ). Subsequently, they found that this highly biocompatible and soluble nanotherapeutic agent additionally exhibits a dual PDT/PTT phototoxic effect on NB cells ( Figure 5B ) ( Varon et al, 2022 ).…”

“…(B) AuNP-mTHPC complexes for PDT and PTT dual therapy. Reproduced from ( Varon et al, 2022 ). (C) Photo-magnetic irradiation mediated multimodal therapeutic strategy of NB cells.…”

Erythrocyte membrane-camouflaged Prussian blue nanocomplexes for combinational therapy of triple-negative breast cancer

“…7 In recent years, phototherapy has become an alternative to tumor therapy where the integration of PDT and PTT has demonstrated therapeutic synergism by reciprocally complementing each other and also minimizing the disadvantages of monotherapy. 8…”

“…7 In recent years, phototherapy has become an alternative to tumor therapy where the integration of PDT and PTT has demonstrated therapeutic synergism by reciprocally complementing each other and also minimizing the disadvantages of monotherapy. 8 Although multifunctional nanocomplexes with photodynamic and photothermal properties have been developed for TNBC therapy, apart from the complicated synthesis process, inherent limitations including abnormal blood vessels, high concentrations of H 2 O 2 and hypoxia of the TME still need to be overcome. 9,10 Additionally, the PDT causes the restriction of microvascular circulation, which further aggravates hypoxia of the tumors, leading to unsatisfactory performance.…”