Organelle-Targeted Photosensitizers for Precision Photodynamic Therapy

Wang, Rui; Li, Xingshu; Yoon, Juyoung

doi:10.1021/acsami.1c02019

Cited by 190 publications

(158 citation statements)

References 207 publications

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“…For example, the first generation Ps such as hematoporphyrin derivative localizes diffusely in the cytomembrane and porfimer (Photofrin ® ) localizes to the Golgi apparatus and the endoplasmic reticulum [44,45], while the second generation Ps such as meta-tetrahydroxy-phenylchlorin (Foscan ® ), 5-ALA, and N-aspartyl chlorin e6 accumulates in the Golgi apparatus and endoplasmic reticulum, mitochondria, and lysosome, respectively [46][47][48]. In order for effective PCI to occur, the preferential uptake by endocytosis and accumulation of Ps in the endo-lysosomal axis is a crucial requisite [49,50]; these can be mediated by the conjugation of cell penetrating peptide or low density lipoprotein to the Ps, or through the use of Ps in the form of nanocomposites or nanoparticles [51][52][53]. In this study, the latter approach was utilized through the formation of PAMAM(G5) Ns incorporating both Etop and PpIX.…”

Section: Discussionmentioning

confidence: 99%

Photochemical Internalization of Etoposide Using Dendrimer Nanospheres Loaded with Etoposide and Protoporphyrin IX on a Glioblastoma Cell Line

et al. 2021

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Glioblastoma multiforme (GBM) is the most common malignant primary neoplasm of the adult central nervous system originating from glial cells. The prognosis of those affected by GBM has remained poor despite advances in surgery, chemotherapy, and radiotherapy. Photochemical internalization (PCI) is a release mechanism of endocytosed therapeutics into the cytoplasm, which relies on the membrane disruptive effect of light-activated photosensitizers. In this study, phototherapy by PCI was performed on a human GBM cell-line using the topoisomerase II inhibitor etoposide (Etop) and the photosensitizer protoporphyrin IX (PpIX) loaded in nanospheres (Ns) made from generation-5 polyamidoamine dendrimers (PAMAM(G5)). The resultant formulation, Etop/PpIX-PAMAM(G5) Ns, measured 217.4 ± 2.9 nm in diameter and 40.5 ± 1.3 mV in charge. Confocal microscopy demonstrated PpIX fluorescence within the endo-lysosomal compartment, and an almost twofold increase in cellular uptake compared to free PpIX by flow cytometry. Phototherapy with 3 min and 5 min light illumination resulted in a greater extent of synergism than with co-administered Etop and PpIX; notably, antagonism was observed without light illumination. Mechanistically, significant increases in oxidative stress and apoptosis were observed with Etop/PpIX-PAMAM(G5) Ns upon 5 min of light illumination in comparison to treatment with either of the agents alone. In conclusion, simultaneous delivery and endo-lysosomal co-localization of Etop and PpIX by PAMAM(G5) Ns leads to a synergistic effect by phototherapy; in addition, the finding of antagonism without light illumination can be advantageous in lowering the dark toxicity and improving photo-selectivity.

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Section: Discussionmentioning

confidence: 99%

Photochemical Internalization of Etoposide Using Dendrimer Nanospheres Loaded with Etoposide and Protoporphyrin IX on a Glioblastoma Cell Line

et al. 2021

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“…Recently, Tsourkas and coworkers combined superparamagnetic SPIONs and chlorin e6 (Ce6), a second-generation and clinically used photosensitizer, to develop a theranostic agent for dual-mode imaging and photodynamic therapy [16]. Photodynamic therapy (PDT) is a relatively new modality based on a minimally invasive procedure for spatiotem-porally selective treatments for cancer and other malignant diseases [32,33]. PDT uses light, chemical photosensitizers (PSs), and molecular oxygen or other adjacent substrates to generate cytotoxic reactive oxygen species (ROS) that eradicate target tumor cells.…”

Section: Integration Of Organic Dyes and Magnetic Iron Oxide Nanopart...mentioning

confidence: 99%

Multifunctional Iron Oxide Magnetic Nanoparticles for Biomedical Applications: A Review

et al. 2022

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Due to their good magnetic properties, excellent biocompatibility, and low price, magnetic iron oxide nanoparticles (IONPs) are the most commonly used magnetic nanomaterials and have been extensively explored in biomedical applications. Although magnetic IONPs can be used for a variety of applications in biomedicine, most practical applications require IONP-based platforms that can perform several tasks in parallel. Thus, appropriate engineering and integration of magnetic IONPs with different classes of organic and inorganic materials can produce multifunctional nanoplatforms that can perform several functions simultaneously, allowing their application in a broad spectrum of biomedical fields. This review article summarizes the fabrication of current composite nanoplatforms based on integration of magnetic IONPs with organic dyes, biomolecules (e.g., lipids, DNAs, aptamers, and antibodies), quantum dots, noble metal NPs, and stimuli-responsive polymers. We also highlight the recent technological advances achieved from such integrated multifunctional platforms and their potential use in biomedical applications, including dual-mode imaging for biomolecule detection, targeted drug delivery, photodynamic therapy, chemotherapy, and magnetic hyperthermia therapy.

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“…In fact, not only the ROS generation but also the cellular location of PSs affects the PDT efficiency. Until recently, although a number of PSs have been reported which demonstrate nucleus, mitochondrion, or lysosome location (Wu et al, 2015;Zeng et al, 2017;Li et al, 2019;Wang R. et al, 2021), few PSs for LD location are also reported (Tabero et al, 2020;Zhang et al, 2020;Tan et al, 2021a;Tan et al, 2021b;Zhang et al, 2021). More importantly, the LDtargeted PDT mechanism is under deeper research.…”

Section: Introductionmentioning

confidence: 99%

A Novel Photosensitizer for Lipid Droplet–Location Photodynamic Therapy

Xia

Wang

et al. 2021

Front. Chem.

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Lipid droplets (LDs), an extremely important cellular organelle, are responsible for the storage of neutral lipids in multiple biological processes, which could be a potential target site for photodynamic therapy (PDT) of cancer. Herein, a lipid droplet–targeted photosensitizer (BODSeI) is developed, allowing for fluorescence imaging–guided PDT. Owing to the location of lipid droplets, BODSeI demonstrates enhanced PDT efficiency with an extremely low IC50 value (around 125 nM). Besides, BODSeI shows good biocompatibility and high photostability. Therefore, BODSeI is promising for droplet-location PDT, which may trigger wide interest for exploring the pathway of lipid droplet–location PDT.

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Organelle-Targeted Photosensitizers for Precision Photodynamic Therapy

Cited by 190 publications

References 207 publications

Photochemical Internalization of Etoposide Using Dendrimer Nanospheres Loaded with Etoposide and Protoporphyrin IX on a Glioblastoma Cell Line

Photochemical Internalization of Etoposide Using Dendrimer Nanospheres Loaded with Etoposide and Protoporphyrin IX on a Glioblastoma Cell Line

Multifunctional Iron Oxide Magnetic Nanoparticles for Biomedical Applications: A Review

A Novel Photosensitizer for Lipid Droplet–Location Photodynamic Therapy

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