Plasma membrane activatable polymeric nanotheranostics with self-enhanced light-triggered photosensitizer cellular influx for photodynamic cancer therapy

Hao, Jia; Jiang, Yao; Zhu, Ya‐Xuan; Li, Yan Hong; Wang, Hong Yin; Han, Xiaofeng; Yu, Zhi; Gu, Ning; Liu, Peidang; Chen, Zhan; Wu, Fu‐Gen

doi:10.1016/j.jconrel.2017.04.030

Cited by 81 publications

(61 citation statements)

References 78 publications

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“…Photodynamic therapy (PDT) has been proven to be a potential therapeutic strategy for cancers via the reaction between photosensitizers and oxygen (O 2 ) under laser to generate cytotoxic reactive oxygen species (ROS) for killing cancer cells . Compared to traditional cancer therapy strategies, such as surgery, chemotherapy, and radiotherapy, PDT emerges as a promising treatment method with less invasiveness, fewer side effects, and higher selectivity and efficacy .…”

Section: Introductionmentioning

confidence: 99%

Oxygen‐Evolving Mesoporous Organosilica Coated Prussian Blue Nanoplatform for Highly Efficient Photodynamic Therapy of Tumors

et al. 2018

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Oxygen (O2) plays a critical role during photodynamic therapy (PDT), however, hypoxia is quite common in most solid tumors, which limits the PDT efficacy and promotes the tumor aggression. Here, a safe and multifunctional oxygen‐evolving nanoplatform is costructured to overcome this problem. It is composed of a prussian blue (PB) core and chlorin e6 (Ce6) anchored periodic mesoporous organosilica (PMO) shell (denoted as PB@PMO‐Ce6). In the highly integrated nanoplatform, the PB with catalase‐like activity can catalyze hydrogen peroxide to generate O2, and the Ce6 transform the O2 to generate more reactive oxygen species (ROS) upon laser irradiation for PDT. This PB@PMO‐Ce6 nanoplatform presents well‐defined core–shell structure, uniform diameter (105 ± 12 nm), and high biocompatibility. This study confirms that the PB@PMO‐Ce6 nanoplatform can generate more ROS to enhance PDT than free Ce6 in cellular level (p < 0.001). In vivo, the singlet oxygen sensor green staining, tumor volume of tumor‐bearing mice, and histopathological analysis demonstrate that this oxygen‐evolving nanoplatform can elevate singlet oxygen to effectively inhibit tumor growth without obvious damage to major organs. The preliminary results from this study indicate the potential of biocompatible PB@PMO‐Ce6 nanoplatform to elevate O2 and ROS for improving PDT efficacy.

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Section: Introductionmentioning

confidence: 99%

Oxygen‐Evolving Mesoporous Organosilica Coated Prussian Blue Nanoplatform for Highly Efficient Photodynamic Therapy of Tumors

et al. 2018

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“…According to the confocal imaging results, MEL/Ce6@HA could be rapidly recruited to the plasma membrane of cancer cells. Our previous work has demonstrated that PDT can effectively disrupt cellular membrane structures such as plasma and nuclear membranes by inducing lipid peroxidation . Hence, we anticipate that the photodynamic effect of Ce6 combined with the membrane‐permeabilizing activity of melittin would promote the disruption of cancer cell membranes in a synergistic manner.…”

Section: Resultsmentioning

confidence: 95%

Turning Toxicants into Safe Therapeutic Drugs: Cytolytic Peptide−Photosensitizer Assemblies for Optimized In Vivo Delivery of Melittin

Jia

Zhu

et al. 2018

Adv Healthcare Materials

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Melittin (MEL) is recognized as a highly potent therapeutic peptide for treating various human diseases including cancer. However, the clinical applications of MEL are largely restricted by its severe hemolytic activity and nonspecific cytotoxicity. Here, it is found that MEL can form a stable supramolecular nanocomplex of ≈60 nm with the photosensitizer chlorin e6 (Ce6), which after hyaluronic acid (HA) coating can achieve robust, safe, and imaging-guided tumor ablation. The as-designed nanocomplex (denoted as MEL/Ce6@HA) shows largely reduced hemolysis and selective cytolytic activity toward cancer cells. Upon laser irradiation, the loaded photosensitive Ce6 can synergistically facilitate the membrane-lytic efficiency of melittin and greatly increase the tumor penetration depth of the complexes in multicellular tumor spheroids. In vivo experiments reveal that MEL/Ce6@HA can realize enhanced tumor accumulation, reduced liver deposition, and rapid body clearance, which are beneficial for highly efficient and safe chemo-photodynamic dual therapy. This work develops a unique supramolecular strategy for optimized in vivo delivery of melittin and may have implications for the development of peptide-based theranostics.

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“…In addition, fusogenic liposomes and amphiphilic polymers have also been demonstrated to insert PSs into plasma membranes for enhanced PDT effect. However, to the best of our knowledge, plasma membrane‐targeted PDT remains rarely explored, mainly due to the difficulty of relatively long‐time membrane‐anchoring of PSs.…”

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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Plasma membrane activatable polymeric nanotheranostics with self-enhanced light-triggered photosensitizer cellular influx for photodynamic cancer therapy

Cited by 81 publications

References 78 publications

Oxygen‐Evolving Mesoporous Organosilica Coated Prussian Blue Nanoplatform for Highly Efficient Photodynamic Therapy of Tumors

Oxygen‐Evolving Mesoporous Organosilica Coated Prussian Blue Nanoplatform for Highly Efficient Photodynamic Therapy of Tumors

Turning Toxicants into Safe Therapeutic Drugs: Cytolytic Peptide−Photosensitizer Assemblies for Optimized In Vivo Delivery of Melittin

Recent Advances in Subcellular Targeted Cancer Therapy Based on Functional Materials

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