Acidity‐Triggered Tumor‐Targeted Chimeric Peptide for Enhanced Intra‐Nuclear Photodynamic Therapy

Han, Kai; Zhang, Weiyun; Zhang, Jin; Lei, Qi; Wang, Shibo; Liu, Jiawei; Zhang, Xian‐Zheng

doi:10.1002/adfm.201600170

Cited by 128 publications

(87 citation statements)

References 36 publications

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“…Compared with chemotherapy and radiotherapy, both of which commonly cause serious systemic toxicity, phototherapy has several outstanding merits including minimal invasiveness, high spatiotemporal selectivity and favorable safety . However, phototherapy has also some unresolved challenges . First of all, poor water solubility and poor specific delivery of photosensitizer often induce high toxicity to normal tissues .…”

Section: Introductionmentioning

confidence: 99%

Dye‐Anchored MnO Nanoparticles Targeting Tumor and Inducing Enhanced Phototherapy Effect via Mitochondria‐Mediated Pathway

Zhou

Meng

et al. 2018

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Phototherapy is a promising treatment method for cancer therapy. However, the various factors have greatly restricted phototherapy development, including the poor accumulation of photosensitizer in tumor, hypoxia in solid tumor tissue and systemic phototoxicity. Herein, a mitochondrial-targeted multifunctional dye-anchored manganese oxide nanoparticle (IR808@MnO NP) is developed for enhancing phototherapy of cancer. In this nanoplatform, IR808 as a small molecule dye acts as a tumor targeting ligand to make IR808@MnO NPs with capacity to actively target tumor cells and relocate finally in the mitochondria. Meanwhile, continuous production of oxygen (O ) and regulation of pH induced by the high reactivity and specificity of MnO NPs toward mitochondrial endogenous hydrogen peroxide (H O ) could effectively modulate tumor hypoxia and lessen the tumor subacid environment. Large amounts of reactive oxide species (ROS) are generated during the reaction process between H O and MnO NPs. Furthermore, under laser irradiation, IR808 in IR808@MnO NPs turns O into a highly toxic singlet oxygen ( O ) and generates hyperthermia. The results indicate that IR808@MnO NPs have the high efficiency of specific targeting of tumors, relieving tumor subacid environment, improving the tumor hypoxia environment, and generating large amounts of ROS to kill tumor cells. It is expected to have a wide application in treating cancer.

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Section: Introductionmentioning

confidence: 99%

Dye‐Anchored MnO Nanoparticles Targeting Tumor and Inducing Enhanced Phototherapy Effect via Mitochondria‐Mediated Pathway

Zhou

Meng

et al. 2018

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“…b) Schematic illustration of intranuclear delivery of photosensitizer by chimeric peptide (PAPP–DMA) into cancer cells for enhanced photodynamic therapy. Adapted with permission . Copyright 2016, Wiley‐VCH.…”

Section: Therapeutic Strategies Toward Specific Subcellular Compartmentsmentioning

confidence: 99%

“…Although nuclear transportation could be facilitated by small‐sized nanocarriers, the preparation and modification processes are always arduous. Han and co‐workers designed an easy‐to‐fabricate delivery system by using an amphiphilic chimeric peptide (PAPP–DMA), which comprised an alkylated protoporphyrin IX (PpIX), a PEG linker, and an NLS peptide (sequence: PKKKRKV) modified with acidic liable DMA (Figure b) . In this carefully designed PAPP–DMA system, DMA groups were expected to disguise NLS sequence as well as to protect the nanoparticles from in vivo nonspecific adsorption, but these groups could be removed under the trigger of mildly acidic tumor environment (pH < 6.8).…”

Section: Therapeutic Strategies Toward Specific Subcellular Compartmentsmentioning

confidence: 99%

Recent Advances in Subcellular Targeted Cancer Therapy Based on Functional Materials

2018

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Recently, diverse functional materials that take subcellular structures as therapeutic targets are playing increasingly important roles in cancer therapy. Here, particular emphasis is placed on four kinds of therapies, including chemotherapy, gene therapy, photodynamic therapy (PDT), and hyperthermal therapy, which are the most widely used approaches for killing cancer cells by the specific destruction of subcellular organelles. Moreover, some non-drug-loaded nanoformulations (i.e., metal nanoparticles and molecular self-assemblies) with a fatal effect on cells by influencing the subcellular functions without the use of any drug molecules are also included. According to the basic principles and unique performances of each treatment, appropriate strategies are developed to meet task-specific applications by integrating specific materials, ligands, as well as methods. In addition, the combination of two or more therapies based on multifunctional nanostructures, which either directly target specific subcellular organelles or release organelle-targeted therapeutics, is also introduced with the intent of superadditive therapeutic effects. Finally, the related challenges of critical re-evaluation of this emerging field are presented.

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“…Han et al engineered a chimeric peptide, PAPP‐DMA, for targeted uptake by cells in the acidic TME. The peptide contains PpIX conjugated to a nuclear localization sequence (NLS) that has been modified with a negatively charged 2,3‐dimethylmaleic anhydride (DMA).…”

Section: Targeting the Tumor Microenvironment With Photochemistrymentioning

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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Acidity‐Triggered Tumor‐Targeted Chimeric Peptide for Enhanced Intra‐Nuclear Photodynamic Therapy

Cited by 128 publications

References 36 publications

Dye‐Anchored MnO Nanoparticles Targeting Tumor and Inducing Enhanced Phototherapy Effect via Mitochondria‐Mediated Pathway

Dye‐Anchored MnO Nanoparticles Targeting Tumor and Inducing Enhanced Phototherapy Effect via Mitochondria‐Mediated Pathway

Recent Advances in Subcellular Targeted Cancer Therapy Based on Functional Materials

Photodynamic Therapy and the Biophysics of the Tumor Microenvironment

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