Photodynamic Therapy Induced Enhancement of Tumor Vasculature Permeability Using an Upconversion Nanoconstruct for Improved Intratumoral Nanoparticle Delivery in Deep Tissues

Gao, Weidong; Wang, Zhaohui; Lv, Liwei; Yin, Deyan; Chen, Dan; Han, Zhihao; Ma, Yi; Zhang, Min; Yang, Man; Gu, Yueqing

doi:10.7150/thno.15262

Cited by 91 publications

(56 citation statements)

References 32 publications

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“…Similar results were reported using NaYF 4 :Yb,Er UNCPs surface‐coated with the RGD peptide. [ 121 ] The targeting ability of the UCNPs in PC‐3‐tumor bearing mice was studied using the dye, indocyanine green, further supported the targeting ability of the RGD peptide. A distinct accumulation of RGD‐UCNP conjugate in tumor cells was noted at 4 h post injection, while no distinct signal was noted in the tumors of control animals until 8 h post injection.…”

Section: Strategies For Targeting the Tmementioning

confidence: 99%

Designing Stimuli‐Responsive Upconversion Nanoparticles that Exploit the Tumor Microenvironment

et al. 2020

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Tailoring personalized cancer nanomedicines demands detailed understanding of the tumor microenvironment. In recent years, smart upconversion nanoparticles with the ability to exploit the unique characteristics of the tumor microenvironment for precise targeting have been designed. To activate upconversion nanoparticles, various bio‐physicochemical characteristics of the tumor microenvironment, namely, acidic pH, redox reactants, and hypoxia, are exploited. Stimuli‐responsive upconversion nanoparticles also utilize the excessive presence of adenosine triphosphate (ATP), riboflavin, and Zn2+ in tumors. An overview of the design of stimulus‐responsive upconversion nanoparticles that precisely target and respond to tumors via targeting the tumor microenvironment and intracellular signals is provided. Detailed understanding of the tumor microenvironment and the personalized design of upconversion nanoparticles will result in more effective clinical translation.

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Section: Strategies For Targeting the Tmementioning

confidence: 99%

Designing Stimuli‐Responsive Upconversion Nanoparticles that Exploit the Tumor Microenvironment

et al. 2020

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“…The utilization of the upconversion nanoparticles (UCNPs) could also be a promising strategy for reaching deep-seated tumors with negligible interactions with endogenous molecules [42]. This system can up-convert two or more low-level energy photons (near-infrared light) into one high-energy photon (ultraviolet-visible light) [43].…”

Section: Mitochondrial Targeting Ligand-modified Drug Delivery Systemmentioning

confidence: 99%

Therapeutic Strategies for Regulating Mitochondrial Oxidative Stress

et al. 2020

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There have been many reports on the relationship between mitochondrial oxidative stress and various types of diseases. This review covers mitochondrial targeting photodynamic therapy and photothermal therapy as a therapeutic strategy for inducing mitochondrial oxidative stress. We also discuss other mitochondrial targeting phototherapeutic methods. In addition, we discuss anti-oxidant therapy by a mitochondrial drug delivery system (DDS) as a therapeutic strategy for suppressing oxidative stress. We also describe cell therapy for reducing oxidative stress in mitochondria. Finally, we discuss the possibilities and problems associated with clinical applications of mitochondrial DDS to regulate mitochondrial oxidative stress.Biomolecules 2020, 10, 83 2 of 23 Parkinson's and Alzheimer's diseases, by the direct neutralization of ROS and by suppressing inflammation [5,6]. Furthermore, CoQ 10 , a potent ubiquinone antioxidant, has been reported to show significant protective effects on mitochondria of the pancreatic beta cells during the oxidative stress induced by the chronic use of tacrolimus [7]. Due to the highly hydrophobic characteristics and the fact that most of the antioxidant molecules accumulate in a nonspecific manner, a high dose is needed to obtain the desired effects. Thus, the selective delivery of this compound would be expected to further strengthen its effectivity.In the context of cancer therapy, mitochondrial ROS were found to play an important role as a signaling molecule in controlling cell proliferation by virtue of its ability to regulate the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathway [8]. Moreover, antioxidant activity, such as GSH and thioredoxin, was also reported to be essential for the initiation of and the progression of cancer. Inhibition of the antioxidant activity resulted in a significant reduction in tumor progression and metastasis [9][10][11]. These findings suggest that cancer cells are maintained under conditions of ROS stress and that antioxidant supplementation may be irrelevant for cancer therapy [12][13][14]. However, ROS interact with several major biologically active molecules such as proteins, lipids, and nucleic acids, leading to irreversible oxidative damage and the further induction of lethal effects for the cells. Therefore, promoting ROS production could be a promising strategy for treating tumors. There are numerous methods that can be employed to promote ROS levels in cancers, i.e., depleting or inhibiting antioxidant activity [15,16] and inhibiting the mitochondrial respiratory system [17], and producing an excessive amount of ROS through photochemical reactions. The latter effort shows a high selectivity for tumor cells, making it more encouraging in contrast to other efforts.This review focuses on therapeutic strategies for regulating mitochondrial oxidative stress. The main theme includes therapeutic strategies designed to induce oxidative stress and suppress mitochondrial oxidative stress (Figure 1). As ...

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“…For example, through understanding pharmacokinetics following PS administration, PS-light interval can be optimized to activate PSs while they are accumulated in specific compartments to increase permeability to macromolecules and nanoparticles (8,140,143,264,265). Moreover, targeting moieties can be utilized to achieve accumulation of PSs in the tumor vasculature and perivascular tumor cells to enhance the EPR effect (266)(267)(268).…”

Section: -Fluorouracil Increases Coproporphyrinogenmentioning

confidence: 99%

Photodynamic Therapy and the Biophysics of the Tumor Microenvironment

Sorrin

Ruhi

Ferlic

et al. 2020

Photochem & Photobiology

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Targeting the tumor microenvironment (TME) provides opportunities to modulate tumor physiology, enhance the delivery of therapeutic agents, impact immune response and overcome resistance. Photodynamic therapy (PDT) is a photochemistry‐based, nonthermal modality that produces reactive molecular species at the site of light activation and is in the clinic for nononcologic and oncologic applications. The unique mechanisms and exquisite spatiotemporal control inherent to PDT enable selective modulation or destruction of the TME and cancer cells. Mechanical stress plays an important role in tumor growth and survival, with increasing implications for therapy design and drug delivery, but remains understudied in the context of PDT and PDT‐based combinations. This review describes pharmacoengineering and bioengineering approaches in PDT to target cellular and noncellular components of the TME, as well as molecular targets on tumor and tumor‐associated cells. Particular emphasis is placed on the role of mechanical stress in the context of targeted PDT regimens, and combinations, for primary and metastatic tumors.

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Photodynamic Therapy Induced Enhancement of Tumor Vasculature Permeability Using an Upconversion Nanoconstruct for Improved Intratumoral Nanoparticle Delivery in Deep Tissues

Cited by 91 publications

References 32 publications

Designing Stimuli‐Responsive Upconversion Nanoparticles that Exploit the Tumor Microenvironment

Designing Stimuli‐Responsive Upconversion Nanoparticles that Exploit the Tumor Microenvironment

Therapeutic Strategies for Regulating Mitochondrial Oxidative Stress

Photodynamic Therapy and the Biophysics of the Tumor Microenvironment

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