Adapting and Remolding: Orchestrating Tumor Microenvironment Normalization with Photodynamic Therapy by Size Transformable Nanoframeworks
Tingxizi LiangBenhua ZhangZejing XingYuxiang DongHongmei XuXueqin ChenLiping JiangJun‐Jie ZhuQianhao Min
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Abstract Abnormal tumor microenvironment (TME) facilitates tumor proliferation and metastasis and establishes physiological barriers for effective transport of therapeutics inside the tumor, posing great challenges for cancer treatment. We designed a core‐satellite size transformable nanoframework (denoted as T‐PFRT) that can synchronously adapt to and remold TME for augmenting photodynamic therapy to inhibit tumor growth and prevent tumor metastasis. Upon matrix metalloproteinase 2 (MMP2)‐responsive dissociation of the nanoframework in TME, the core structure loaded with TGFβ signaling pathway inhibitor and oxygen‐carrying hemoglobin aims to stroma remodeling and hypoxia relief, allowing photosensitizer‐encapsulated satellite particles to penetrate to deep‐seated tumor for oxygen‐fueled photodynamic therapy. T‐PFRT could overcome the stroma and hypoxia barriers for delivering therapeutics and gain excellent therapeutic outcomes in the treatment of primary and metastatic tumors.Keywords:
Tumor Hypoxia
Hypoxia
Photodynamic Therapy(PDT) was a new technology for disease diagnosis and treatment with photosensitizer conducting photodynamic reaction.Photosensitizer was gradually matured through the first-generation photosensitizers-porphyrin and its derivatives,second-generation photosensitizer-phthalocyanine compounds,as well as third-generation photo-sensitizer.The property and synthesis of the three generations of photosensitizers were described.
First generation
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Photodynamic therapy (PDT) requires a photosensitizer, light, and oxygen to induce cell death. The majority of efforts to advance PDT focus only on the first two components. Here, we employ perfluorocarbon nanoemulsions to simultaneously deliver oxygen and a photosensitizer. We find that the implementation of fluorous soluble photosensitizers enhances the efficacy of PDT.
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Photodynamic sensitizers are drugs activated by light of a specific wavelength and are used in the photodynamic therapy (PDT) of certain diseases. Second‐ and third‐generation photosensitizers with improved PDT properties are now under investigation. In this issue of the British Journal of Pharmacology , Leung et al . have described the synthesis and investigation of a second‐generation photosensitizer (BAM‐SiPc) targeted towards the cells of HepG2 and HT29 tumours. BAM‐SiPc is selectively functionalized with bis‐amino groups and has demonstrated potent PDT activity in a small animal model. However, it also exhibited non‐selective distribution and accumulation in multiple animal (small mouse) organs and tissue. These issues highlight the importance and need for good biodistribution and localization properties for an efficacious photosensitizer. The lack of tumour specificity may have a significant impact on the potential BAM‐SiPc has in clinical PDT.
Biodistribution
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Photodynamic therapy (PDT) kills cancer cells by converting tumour oxygen into reactive singlet oxygen ((1)O2) using a photosensitizer. However, pre-existing hypoxia in tumours and oxygen consumption during PDT can result in an inadequate oxygen supply, which in turn hampers photodynamic efficacy. Here to overcome this problem, we create oxygen self-enriching photodynamic therapy (Oxy-PDT) by loading a photosensitizer into perfluorocarbon nanodroplets. Because of the higher oxygen capacity and longer (1)O2 lifetime of perfluorocarbon, the photodynamic effect of the loaded photosensitizer is significantly enhanced, as demonstrated by the accelerated generation of (1)O2 and elevated cytotoxicity. Following direct injection into tumours, in vivo studies reveal tumour growth inhibition in the Oxy-PDT-treated mice. In addition, a single-dose intravenous injection of Oxy-PDT into tumour-bearing mice significantly inhibits tumour growth, whereas traditional PDT has no effect. Oxy-PDT may enable the enhancement of existing clinical PDT and future PDT design.
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Photodynamic therapy (PDT) is a noninvasive technique for diagnosis and therapy of diseases by using the photodynamic effects. Clinically, PDT has been used in the treatments of various tumors in head and neck, pancreas, lung, prostate and skin. Compared to the traditional treatments of tumors, PDT exhibits many advantages such as less damage, low toxicity, good selectivity, wide applicability and less drug resistance, which draw more attention in the field of tumor therapy. The action mechanisms of PDT against tumors are very complicated and photosensitizer is one of the key factors that influence the photodynamic effects of PDT. To enhance the tumor-targeted delivery of photosensitizer and improve their oxygen-carrying ability are believed as the important ways to increase the photodynamic effects. In this paper, review is given on the research advances in action mechanisms of photodynamic therapy and photosensitizer in recent years.
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Photodynamic therapy; Photosensitizer; Action mechanism
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Photodynamic therapy (PDT) requires photosensitizer, light, and oxygen to induce cell death. The majority of efforts to advance PDT focus only on the first two components. Here, we employ perfluorocarbon nanoemulsions to simultaneously deliver oxygen and photosensitizer. We find that the implementation of fluorous soluble photosensitizers enhances the efficacy of PDT.
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Photodynamic therapy (PDT) is a treatment applied by a laser system in combination with a photosensitive drug (photosensitizer) that is excited by laser light. Accumulation of the photosensitizer at the disease site and local excitation by laser irradiation make it possible to selectively treat the diseased region, preserving the functionality and appearance of the treated area. Photodynamic Diagnosis (PDD) enables the identification of a specific disease site through the capturing of fluorescence generated by the photosensitizer. It is expected PDD will prove useful in identifying the disease site for Glioblastoma, amalignant brain tumor for which clear boundaries cannot be easily detected.
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<p>Photodynamic therapy (PDT) requires photosensitizer, light, and oxygen to induce cell death. The majority of efforts to advance PDT focus only on the first two components. Here, we employ perfluorocarbon nanoemulsions to simultaneously deliver oxygen and photosensitizer. We find that the implementation of fluorous soluble photosensitizers enhances the efficacy of PDT. </p>
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Photodynamic Therapy (PDT) is a new method developed from last century to treat series of malignant tumor,superficial or intracavitary benign lesion by injection of photosensitiser systemic or local application,then a special wave-length light is used to treat the lesion.As an influential factor,Photosensitiser plays an important role in PDT.This article summarized the mechanism of PDT,characteristic and photochemistry of photosensitizer,focus on the uptake,distribution and effect in PDT of photosensitiser.
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