ORGANIC & BIOMOLECULAR CHEMISTRY
·
2019
·Vol. 17
·期 34
·8001-8007
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IF 3.49
Chengjun Wang,Ying Qian
A novel photosensitizer BDPI-lyso has been developed for photodynamic therapy (PDT). The photosensitizer BDPI-lyso showed a high singlet oxygen quantum yield (ΦΔ = 0.95) and low fluorescence quantum yield (ΦF = 0.05) in EtOH. Different singlet oxygen quantum yields were found in acidic solution (pH = 5, ΦΔ = 0.51) and in neutral solution (pH = 7, ΦΔ = 0.38). DFT and TD-DFT calculations of BDPI-lyso and its protonated product BDPI-lysoH+ indicated that the S1/T3 transition was responsible for the intersystem crossing (ISC) enhancement which would promote the production of singlet oxygen. The negligible dark cytotoxicity toward the hepatoma cell line Bel-7402 was confirmed by MTT assay, AO/EB dual staining, and cell images. Upon exposure to a low dose of light illumination, the disruption of the cell plasma membrane and the calculated half-maximal inhibitory concentration (IC50) of 0.4 μM showed a high phototoxicity of the photosensitizer BDPI-lyso. The light-induced intracellular ROS generation was verified as the PDT mechanism of BDPI-lyso. Colocalization experiments of LysoTracker Green and BDPI-lyso in the dark indicated the good lysosome-targeting ability of BDPI-lyso. The images of cells costained with LysoTracker Green and BDPI-lyso, and the appearance of intracellular and extracellular blebs with green fluorescence after light illumination revealed the light-induced dysfunction of lysosomes and cell apoptosis.
研究领域:
生物化学
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医学
·
药物化学
✓ 已验证
DOI
PubMed
高影响因子
Applied Materials Today
·
2025
·
IF 6.9
Jiaxin Li,Yanzhi Xing,Han Leng,Qi Han,Yanfeng Zhang,Jianhua Wang,Xuwei Chen
The combination of photothermal therapy (PTT) and reactive oxygen species (ROS)-involved photodynamic therapy (PDT) holds great promise in enhancing anticancer effect. Herein, a MoS 2 -based multifunctional biomimetic nanotherapeutic platform for synergistic PTT and PDT anti-tumor therapy and real-time self-evaluation of therapeutic effect was developed. MoS 2 hollow nanospheres and fluorescence TAPP-Ma was cloaked with a 4T1 cell-activated fibroblast cell (CM-AF) hybrid membrane to give nanosystem CM-AF-MoS 2 @TAPP-Ma. The hybrid membrane as a delivery system not only offers the nanotherapeutic platform with homotypic targeting ability, but also effectively eliminates the barrier effect of tumor tissue microenvironment. Caspase 3 (Casp3) inside cancer cells activated by the PTT effect of MoS 2 hollow nanospheres broken down TAPP-Ma, triggering the PDT of TAPP. At the same time, the fluoresce “turn-off” of TAPP-Ma provided the base for the self-evaluation of therapeutic effect. The in vitro and in vivo outcomes suggested that the MoS 2 -based multifunctional biomimetic nanotherapeutic platform exhibited synergistic cascade effect for cancer therapy, making it an promising anti-cancer candidate in biomedical clinical application.
研究领域:
生物医学工程
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肿瘤学
·
纳米医学
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产品关联
DOI
高影响因子
LASERS IN MEDICAL SCIENCE
·
2025
·Vol. 40
·期 1
·1-11
·
IF 2.4
Ma Dan,Lu Huixiang,Zhang Hai,Liao Anru,Peng Qianrong,Yang Min
Hypoxia poses a significant challenge to the efficacy of photodynamic therapy (PDT) for cancer treatment. This study aims to design and synthesize PEGylated liposomes encapsulating MnO₂, indocyanine green (ICG), and H-chain ferritin (HFn) to potentially address hypoxia and enhance the therapeutic outcomes of PDT. PEGylated liposomes (ICG/MnO₂-HFn-mPEG-DSPE-Lip) were constructed with a rod-like structure, incorporating MnO₂ as a hypoxia-modulating agent and ICG as a photosensitizer. The drug loading capacity, stability and safety of liposomes were characterized. Singlet oxygen quantum yield (Φ Δ ) was measured under simulated tumor microenvironment conditions. In vitro phototoxicity was evaluated using A549 human lung adenocarcinoma cells. Liposomes have a high drug loading capacity, good biocompatibility and good long-term stability. Under tumor-simulated conditions, Φ Δ was significantly improved, increasing from 0.210 for free ICG to 0.507. The liposomes demonstrated remarkable phototoxic effects on A549 cells (90.5% cell death under combined PDT/PTT vs. 15% for free ICG). This nanoplatform proposes a novel strategy to overcome hypoxia-induced PDT resistance, and the enhanced efficacy may be attributed to the increased oxygen supply mediated by MnO 2 carried by HFn. These findings provide important insights for the development of next-generation therapeutic systems targeting tumor hypoxia.
研究领域:
药学
·
肿瘤学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2019
·
IF 6.638
Bingjun Sun,Yao Chen,Han Yu,Chen Wang,Xuanbo Zhang,Hanqing Zhao,Qin Chen,Zhonggui He,Cong Luo,Jin Sun
The combination of chemotherapy with photodynamic therapy (PDT) holds promising applications in cancer therapy. However, co-encapsulation of chemotherapeutic agents and photosensitizers (PS) into the conventional nanocarriers suffers from inefficient co-loading and aggregation-caused quenching (ACQ) effect of PS trapped in dense carrier materials. Herein, we report a light-activatable photodynamic PEG-coated prodrug nanoplatform for core–shell synergistic chemo-photodynamic therapy. A novel photodynamic polymer is rationally designed and synthesized by conjugating pyropheophorbide a (PPa) to polyethylene glycol 2000 (PEG 2k ). PPa is used as the hydrophobic and photodynamic moiety of the amphipathic PPa-PEG 2k polymer. Then, a core–shell nanoassembly is prepared, with an inner core of a reactive oxygen species (ROS)-responsive oleate prodrug of paclitaxel (PTX) and an outer layer of PPa-PEG 2k . PPa-PEG 2k serves for both PEGylation and PDT. Instead of being trapped in the inner core, PPa in the outer PPa-PEG 2k layer significantly alleviates the ACQ effect. Under laser irradiation, ROS generated by PPa-PEG 2k not only is used for PDT but also synergistically promotes PTX release in combination with the endogenous ROS overproduced in tumor cells. The photodynamic PEG-coated nanoassemblies demonstrated synergistic antitumor activity in vivo . Such a unique nanoplatform, with an inner chemotherapeutic core and an outer photodynamic PEG shell, provides a new strategy for synergistic chemo-photodynamic therapy. Statement of Signification The combination of chemotherapy with photodynamic therapy (PDT) holds promising prospects in cancer therapy. However, it remains a tremendous challenge to effectively co-deliver chemotherapeutic drugs and photosensitizers into tumors. Herein, we construct a photodynamic PEGylation-coated prodrug-nanoplatform for high-efficiency synergistic cancer therapy, which is composed of a light-activatable PPa-PEG 2k shell and a ROS-responsive paclitaxel (PTX) prodrug core. The PPa-PEG 2k -generated ROS not only was used for synergistic PTX release but also synergistically facilitated tumor cell apoptosis in combination with PTX-initiated chemo-cytotoxicity. The light-activatable nanoassemblies exhibited multiple drug delivery advantages including high co-loading efficiency, self-enhanced PTX release, extended circulation time, favorable biodistribution , and potent synergistic anticancer activity. Our findings provide a new strategy for the rational design of advanced nano-DDS for high-efficiency combinational chemo-photodynamic therapy.
研究领域:
肿瘤学
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药剂学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2018
·Vol. 6
·期 41
·6534-6543
·
IF 4.776
Lizhen Zhang,Zhaoxing Lin,Yun-Xiang Yu,Bang-Ping Jiang,Xing-Can Shen
It is of vital importance to engineer the surface structures of carbon dots (CDs) to satisfy their practical biomedical applications, including imaging and treatment. In this work, one type of hyaluronic acid-derived CD (HA-CD) was synthesized via a facile one-step hydrothermal method using cancer cell-targeted HA as a precursor. The as-prepared HA-CDs were targeted actively toward CD44 receptor-overexpressing cancer cells because a partial HA structure remained on the HA-CD surface. Beyond this, HA-CDs can act as a novel photosensitizer, because they can generate O2˙− under 650 nm laser irradiation, and they also exhibit excellent blue photoluminescence emission. The in vitro results revealed that HA-CDs imaged selectively CD44-overexpressing cancer cells and inhibited their growth under 650 nm laser irradiation. Thus, HA-CDs can serve as a promising self-targeted imaging-guided photodynamic therapy (PDT) agent for cancer. The present research provides a promising new method to simply construct multifunctional CD-based targeted phototheranostic systems.
研究领域:
生物医学工程
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肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2017
·Vol. 9
·期 25
·8825-8833
·
IF 7.367
Zhen Hu,Cheng Wang,Feng Zhao,Xirong Xu,Shuhong Wang,Long Yu,Dayu Zhang,Yudong Huang
The wonderful chemical structures and characteristics of low-dimensional carbon materials have exciting applications in life sciences. In the present study, we developed a facile strategy to conjugate C60 with graphene via host–guest chemistry for targeted phototherapy. A versatile carrier based on folic acid-functionalized graphene (GO-FA) and comprising γ-cyclodextrin (γ-CD) at its surface was assembled via π–π interaction, creating hybrid structures with drug storage and tumor targeting properties. This γ-CD-modified graphene (GO-FA/Py-γ-CD) is capable of hosting pristine C60 molecules for the fabrication of a GO-FA/Py-γ-CD/C60 nanohybrid. The hybridization of GO-FA, γ-CD, and C60 hinders the aggregation of C60, promotes cellular uptake, enhances light absorption, and finally demonstrates enhanced phototherapy effects of GO-FA/Py-γ-CD/C60. Under Xe lamp irradiation (2 W cm−2) for 4 min, GO-FA/Py-γ-CD/C60 simultaneously causes heating and intracellular ROS production, which further significantly reduces the cell viability to 16.2% at low content of loading (30 μg mL−1). Moreover, it represents an excellent tumor killing efficiency, better than that of the other reported graphene/C60 nanohybrids; thus, this material is suitable for applications in phototherapy of cancer.
研究领域:
生物医学工程
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纳米医学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2021
·
IF 12.479
Ruomeng Li,Xue Gong,Chen Hong,Hong Wang,Yingying Chen,Kaiyue Tan,Xiaoqing Liu,Fuan Wang
Extracellular vesicles (EVs) have been emerged as versatile drug delivery vehicles due to their outstanding biocompatibility and long-term circulation, yet are constrained with low targeting property and inefficient loading capacity from post-synthetic passive EVs encapsulation. Herein, we report a simple and feasible in situ biosynthetic approach to encapsulate tumor-targeting folate (FA)-modified EVs with intracellularly produced protoporphyrin X (PpIX) and doxorubicin (DOX). As compared with the traditional directly drug-incubated or drug-electroporated EVs, these biosynthesized EVs revealed high drug-loading efficiency with minimized structural and functional perturbations. Our multifunctional EVs revealed the enhanced accumulation and penetration into deep tumor parenchyma, as well as the strengthened immune response to ablate orthotopic and metastatic tumors, thus realizing the more reliable photochemotherapy. As an intelligent multi-mode therapeutic system, our biosynthetic EVs could be engineered with more therapeutic agents and show great promise for biomedicine applications.
研究领域:
生物医学工程
·
肿瘤学
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2022
·
IF 5.364
Han Sun,Ruihua Guo,Yanhui Guo,Jitao Song,Zhiliang Li,Fengling Song
As the most successful clinically approved photosensitizers, porphyrins have been extensively employed in the photodynamic therapy (PDT) of cancers. However, their poor water solubility, aggregation-induced self-quenching on ROS generation, and a low tolerance for a hypoxic condition usually result in unsatisfied therapeutic outcomes. Therefore, great efforts have been dedicated to improving the PDT efficacy of porphyrin-type photosensitizers in treating hypoxic tumors, including combination with additional active components or therapies, which can significantly complicate the therapeutic process. Herein, we report a novel water-soluble porphyrin with O-linked cationic side chains, which exhibits good water solubility, high photostability, and significantly enhanced ROS generation efficacy in both type-I and type-II photodynamic pathways. We have also found that the end charges of side chains can dramatically affect the ROS generation of the porphyrin. The cationic porphyrin exhibited high in vitro PDT efficacy with low IC50 values both in normoxia and hypoxia. Hence, during in vivo PDT study, the cationic porphyrin displayed highly effective tumor ablation capability. This study demonstrates the power of side-chain chemistry in tuning the photodynamic property of porphyrin, which offers a new effective strategy to enhance the anticancer performance of photosensitizers for fulfilling the increasing demands for cancer therapy in clinics.
研究领域:
药理学
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肿瘤学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DYES AND PIGMENTS
·
2022
·
IF 5.122
Yuanyuan Zhang,Jing Wang,Wanlu Sun,Hui Yu,Shubo An,Hai-Yan Wang,Yi Liu
Increasing interest has been noted in photosensitizer design. Currently, most small molecular photosensitizers have several drawbacks, including limited penetration depth and unsatisfying photostability. For addressing these limitations, Frequency upconversion luminescence (FUCL) small molecule was adopted as a photosensitizer design strategy for its deeper penetration, sensitive imaging, and better photostability. We developed a series of FUCL (NIR-NH 2 , NIR-NHEt, NIR-NEt 2 ) molecules with rigid structures. Equipped with the most powerful electron donor , NIR-NEt 2 exhibits the highest singlet oxygen generation, the strongest upconversion luminescence intensity under 808 nm irradiation and mitochondria-targeted ability. FUCL can be a superior molecular platform for image-guided photodynamic therapy of cancer cells.
研究领域:
化学
·
肿瘤学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2022
·
IF 5.518
Yuguang Yang,Wei Cui,Jie Zhao
Drug resistance is the main challenge in cancer treatment by chemotherapy. To overcome the problems, photodynamic therapy (PDT) can be introduced to increase the internalization of chemotherapeutics. Herein, we design and fabricate core-shell nanostructures for the increased therapy effect of drug resistant cancers. Human serum albumin (HSA) is conjugated with Rose Bengal (RB) (HSA-RB) to improve the endocytosis efficiency of the photosensitizer . Then we fabricated a core-shell nanostructure by coating with doxorubicin (DOX)-loaded CaCO 3 (CaCO 3 @DOX) with HSA-RB and dialdehyde carboxymethyl cellulose (DCMC) via a layer-by-layer technique. The formed CaCO 3 @DOX@(HSA-RB/DCMC) n nanostructures can be easily endocytosed by DOX resistant cancer cells (MCF-7/ADR) in the presence of low dose PDT, and greatly prevent the proliferation of cancer cells by the synergistic effect of PDT and chemotherapy. The nanostructures present efficient methods to solve drug resistance problems in the cure of cancers.
研究领域:
肿瘤学
·
药理学
·
生物医学工程
✓ 已验证
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Jiayang Luo,Luyao Xu,Jing Feng,Kexin Xu,Peilin Tian,Xianyue Bai,Shihao Xu,Liewei Wen,Cuixia Lu,Jiaxing Song
Photodynamic therapy (PDT) induces apoptosis in cancer cells by generating cytotoxic reactive oxygen species (ROS); however, this effect is constrained by the intrinsic antioxidant mechanisms of the cells and the hypoxic conditions of the tumor microenvironment (TME). To overcome these limitations, a novel ferroptosis-boosted nanophotosensitizer (FCE NPs) is developed after loading alkaloid evodiamine based on an acid-responsive nanoplatform (FC NPs) composed of ferric ions and Chlorin e6 (Ce6). Upon exposure to laser irradiation, the photosensitizer Ce6 efficiently generates singlet oxygen (1O2), which depletes glutathione (GSH), thereby disrupting the redox homeostasis within tumor cells and leading to the oxidation of cellular unsaturated lipid into lipid peroxides (LPO). Additionally, the Fenton reaction between released Fe(III) ions and H2O2 in the TME produces highly cytotoxic hydroxyl radicals (•OH), a form of ROS, causing the accumulation of LPO together with 1O2 to trigger ferroptosis. Following the incorporation of evodiamine, the integrated nanoplatform FCE NPs exhibited excellent antitumor activity through high-performance ferroptosis by inhibiting a glutathione peroxidase 4 (GPX4) level. It was also observed that the key regulator of Wnt signaling pathway β-catenin was downregulated, suggesting the inhibition of FCE NPs on the Wnt signaling pathway. Therefore, this study demonstrated that the FCE NPs could lead to the explosive production of ROS and simultaneous inhibition of GPX4/GSH pathways and the Wnt signaling pathway in colorectal cancer, significantly amplifying the tumoricidal efficacy of PDT through the synergistical sensitization of ferroptosis. This approach offers a promising strategy for the clinical application of ferroptosis therapy.
研究领域:
生物学
·
医学
·
肿瘤学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2017
·
IF 5.246
Xiaomei Dai,Xuelei Chen,Yu Zhao,Yunjian Yu,Xiaosong Wei,Xinge Zhang,Chaoxing Li
A multitude of serious chronic infections are involved in bacterial biofilms that are difficult to eradicate. Here, a water-soluble galactose-functionalized cationic 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY)-based photodynamic therapy agent was synthesized for selectively eliminating the bacterial biofilm. These conjugates can capture bacteria to form aggregations through electrostatic interaction and then generate a large number of reactive oxygen species (ROS) under visible light irradiation to kill the bacteria without the emergence of bacterial resistance. Simultaneously, this agent could effectively inhibit and eradicate both Gram-positive and Gram-negative bacterial biofilms. The in-depth analysis of the antimicrobial mechanism confirmed that the conjugates can quickly bind on the bacterial surface, irreversibly disrupt the bacterial membrane, and distinctly inhibit intracellular enzyme activity, ultimately leading to the bacterial death. Importantly, these conjugates are highly selective toward bacterial cells over mammalian cells as well as no cytotoxicity to A549 cells and no discernible hemolytic activity. Collectively, this water-soluble galactose-decorated cationic BODIPY-based photodynamic therapy agent design provides promising insights for the development of therapy for antibiotic-resistant bacteria.
研究领域:
微生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）