Nanoengineering of newly designed chlorin e6 derivative for amplified photodynamic therapy via regulating lactate metabolism

Nanoscale ◽  
2021 ◽  
Author(s):  
Xiaohan Qin ◽  
Mengzhu Zhang ◽  
Xu Hu ◽  
Qian Du ◽  
Zhipeng Zhao ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Therapeutic Efficacy ◽  
Chlorin E6 ◽  
Lactate Metabolism

Chlorin e6 (Ce6) is a widely utilized photosensitizer in photodynamic therapy (PDT) against tumor growth, but its hydrophobic feature and the hypoxia in tumor microenvironment greatly compromise its therapeutic efficacy....

Oxygen-producing proenzyme hydrogels for photodynamic mediated metastasis-inhibited combinational therapy

2021 ◽  
Author(s):  
Jiansheng Liu ◽  
Xueqin Qing ◽  
Qin Zhang ◽  
Ningyue Yu ◽  
Mengbin Ding ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Tumor Microenvironment ◽  
Solid Tumors ◽  
Therapeutic Efficacy ◽  
Tumor Metastasis ◽  
Combinational Therapy ◽  
Hypoxic Tumor

Photodynamic therapy (PDT) has provided a promising approach for treatment of solid tumors, while the therapeutic efficacy is often limited due to hypoxic tumor microenvironment, resulting in tumor metastasis. We...

scholarly journals Programmable Ce6 Delivery via Cyclopamine Based Tumor Microenvironment Modulating Nano-System for Enhanced Photodynamic Therapy in Breast Cancer

2019 ◽  
Vol 7 ◽  
Author(s):  
Chan Feng ◽  
Lv Chen ◽  
Yonglin Lu ◽  
Jie Liu ◽  
Shujing Liang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Photodynamic Therapy ◽  
Tumor Microenvironment ◽  
Cancer Cell Line ◽  
Chlorin E6 ◽  
Great Promise ◽  
Tissue Destruction ◽  
Mice Model ◽  
Cell Internalization

Photodynamic therapy (PDT) has shown great promise in breast cancer treatment. However, simplex target ligand modification or stimuli release cannot meet the requirement of effective drug delivery to solid tumor tissue. To overcome continuous bio-barriers existing in the tumor microenvironment, multi-stage response drug delivery was desirable. Herein, we developed a unique tumor microenvironment tailored nanoplatform for chlorin e6 (Ce6) delivery. We chose bovine serum albumin (BSA) as “mother ships” material for effective tumor periphery resident, cyclopamine (CYC) as extracellular matrix (ECM) inhibitor and synergistic anti-tumor agent, and diselenide containing amphiphilic hyaluronic acid-chlorin e6 polymers (HA-SeSe-Ce6) synthesized as “small bombs” for internal tissue destruction. The above three distinct function compositions were integrated into an independent CYC and HA-SeSe-Ce6 co-delivery albumin nano-system (ABN@HA-SeSe-Ce6/CYC). The obtained nano-system presents good biocompatible, long circulation and effective tumor accumulation. After entering tumor microenvironment, CYC gradually releases to disrupt the ECM barrier to open the way for further penetration of HA-SeSe-Ce6. Subsequently, targeted tumor cell internalization and intracellular redox response release of Ce6 would achieve. Moreover, CYC could also make up the deficiency of Ce6 in hypoxia area, owing to its anti-tumor effect. Improved therapeutic efficacy was verified in a breast cancer cell line and tumor-bearing mice model.

scholarly journals Photodynamic therapy of the experimental tumors of different morphological types with liposomal boronated chlorin е6

2021 ◽  
Vol 10 (3) ◽  
pp. 12-22
Author(s):  
O. B. Abramova ◽  
V. V. Drozhzhina ◽  
T. P. Churikova ◽  
E. A. Kozlovtceva ◽  
L. M. Arkhipova ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Tumor Growth ◽  
Antitumor Effect ◽  
Tumor Regression ◽  
Radiation Energy ◽  
Chlorin E6 ◽  
Radiation Energy Density ◽  
Complete Tumor Regression ◽  
Complete Tumor

The article summarizes the results of studies of the effectiveness of photodynamic therapy using a new domestic photosensitizer liposomal borated chlorin e6 (LBC) after its parenteral administration (intraperitoneal and intravenous). Antitumor efficacy was evaluated in rats with M-1 sarcoma and PC-1 alveolar liver cancer and mice with B16 melanoma and Ehrlich’s carcinoma, which were transplanted subcutaneously into the thigh area of the animals. The aim of the study was to determine the optimal regimes of photodynamic therapy that would allow achieving the maximum antitumor effect up to 21 days after the photodynamic therapy. The therapy was carried out under the control of the accumulation of the photosensitizer in the tumor and surrounding tissues of the thigh by selecting the doses of the drug and the parameters of laser radiation (energy density and power density). The effectiveness of therapy was assessed by the inhibition of tumor growth, by the percentage of animals with complete tumor regression, by the absolute growth rate in animals with continued tumor growth compared to controls. The results of our studies have shown that the domestic photosensitizer liposomal borated chlorin e6 has high antitumor activity in vivo. In an experimental study of the photosensitizer under certain PDT modes, the maximum antitumor effect (complete tumor regression in 100% of animals) was obtained up to 21 days after PDT in all tumor models used.

scholarly journals 695 Oral delivery of a microbial extracellular vesicle induces potent anti-tumor immunity in mice

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A737-A737
Author(s):  
Loise Francisco-Anderson ◽  
Loise Francisco-Anderson ◽  
Mary Abdou ◽  
Michael Goldberg ◽  
Erin Troy ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Extracellular Vesicles ◽  
Tumor Immunity ◽  
Extracellular Vesicle ◽  
The Body ◽  
Checkpoint Inhibition ◽  
Small Intestinal ◽  
The Impact

BackgroundThe small intestinal axis (SINTAX) is a network of anatomic and functional connections between the small intestine and the rest of the body. It acts as an immunosurveillance system, integrating signals from the environment that affect physiological processes throughout the body. The impact of events in the gut in the control of tumor immunity is beginning to be appreciated. We have previously shown that an orally delivered single strain of commensal bacteria induces anti-tumor immunity preclinically via pattern recognition receptor-mediated activation of innate and adaptive immunity. Some bacteria produce extracellular vesicles (EVs) that share molecular content with the parent bacterium in a particle that is roughly 1/1000th the volume in a non-replicating form. We report here an orally-delivered and gut-restricted bacterial EV which potently attenuates tumor growth to a greater extent than whole bacteria or checkpoint inhibition.MethodsEDP1908 is a preparation of extracellular vesicles produced by a gram-stain negative strain of bacterium of the Oscillospiraceae family isolated from a human donor. EDP1908 was selected for its immunostimulatory profile in a screen of EVs from a range of distinct microbial strains. Its mechanism of action was determined by ex vivo analysis of the tumor microenvironment (TME) and by in vitro functional studies with murine and human cells.ResultsOral treatment of tumor-bearing mice with EDP1908 shows superior control of tumor growth compared to checkpoint inhibition (anti-PD-1) or an intact microbe. EDP1908 significantly increased the percentage of IFNγ and TNF producing CD8+ CTLs, NK cells, NKT cells and CD4+ cells in the tumor microenvironment (TME). EDP1908 also increased tumor-infiltrating dendritic cells (DC1 and DC2). Analysis of cytokines in the TME showed significant increases in IP-10 and IFNg production in mice treated with EDP1908, creating an environment conducive to the recruitment and activation of anti-tumor lymphocytes.ConclusionsThis is the first report of striking anti-tumor effects of an orally delivered microbial extracellular vesicle. These data point to oral EVs as a new class of immunotherapeutic drugs. They are particularly effective at harnessing the biology of the small intestinal axis, acting locally on host cells in the gut to control distal immune responses within the TME. EDP1908 is in preclinical development for the treatment of cancer.Ethics ApprovalPreclinical murine studies were conducted under the approval of the Avastus Preclinical Services’ Ethics Board. Human in vitro samples were attained by approval of the IntegReview Ethics Board; informed consent was obtained from all subjects.

scholarly journals A TLR4 agonist improves immune checkpoint blockade treatment by increasing the ratio of effector to regulatory cells within the tumor microenvironment

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
A. Farias ◽  
A. Soto ◽  
F. Puttur ◽  
C. J. Goldin ◽  
S. Sosa ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Therapeutic Effect ◽  
Immune Cells ◽  
Immune Checkpoint ◽  
Combined Treatment ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Regulatory Cells ◽  
Ifn Γ

AbstractBrucella lumazine synthase (BLS) is a homodecameric protein that activates dendritic cells via toll like receptor 4, inducing the secretion of pro-inflammatory cytokines and chemokines. We have previously shown that BLS has a therapeutic effect in B16 melanoma-bearing mice only when administered at early stages of tumor growth. In this work, we study the mechanisms underlying the therapeutic effect of BLS, by analyzing the tumor microenvironment. Administration of BLS at early stages of tumor growth induces high levels of serum IFN-γ, as well as an increment of hematopoietic immune cells within the tumor. Moreover, BLS-treatment increases the ratio of effector to regulatory cells. However, all treated mice eventually succumb to the tumors. Therefore, we combined BLS administration with anti-PD-1 treatment. Combined treatment increases the outcome of both monotherapies. In conclusion, we show that the absence of the therapeutic effect at late stages of tumor growth correlates with low levels of serum IFN-γ and lower infiltration of immune cells in the tumor, both of which are essential to delay tumor growth. Furthermore, the combined treatment of BLS and PD-1 blockade shows that BLS could be exploited as an essential immunomodulator in combination therapy with an immune checkpoint blockade to treat skin cancer.

Porphyrin-lipid nanovesicles (Porphysomes) are effective photosensitizers for photodynamic therapy

Nanophotonics ◽  
2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Keegan Guidolin ◽  
Lili Ding ◽  
Juan Chen ◽  
Brian C. Wilson ◽  
Gang Zheng
Keyword(s):  
Photodynamic Therapy ◽  
Tumor Growth ◽  
Intrinsic Structure ◽  
Therapeutic Applications ◽  
Positron Emission ◽  
Theranostic Agents ◽  
Negative Controls ◽  
And Control ◽  
Complete Tumor

Abstract Porphysomes (PS) are liposome-like nanoparticles comprising pyropheophorbide-conjugated phospholipids that have demonstrated potential as multimodal theranostic agents for applications that include phototherapies, targeted drug delivery and in vivo fluorescence, photoacoustic, magnetic resonance or positron emission imaging. Previous therapeutic applications focused primarily on photothermal therapy (PTT) and suggested that PSs require target-triggered activation for use as photodynamic therapy (PDT) sensitizers. Here, athymic nude mice bearing subcutaneous A549 human lung tumors were randomized into treatment and control groups: PS-PDT at various doses, PS-only and no treatment negative controls, as well as positive controls using the clinical photosensitizer Photofrin. Animals were followed for 30 days post-treatment. PS-PDT at all doses demonstrated a significant tumor ablative effect, with the greatest effect seen with 10 mg/kg PS at a drug-light interval of 24 h. By comparison, negative controls (PS-only, Photofrin-only, and no treatment) showed uncontrolled tumor growth. PDT with Photofrin at 5 mg/kg and PS at 10 mg/kg demonstrated similar tumor growth suppression and complete tumor response rates (15 vs. 25%, p = 0.52). Hence, porphysome nanoparticles are an effective PDT agent and have the additional advantages of multimodal diagnostic and therapeutic applications arising from their intrinsic structure. Porphysomes may also be the first single all-organic agent capable of concurrent PDT and PTT.

scholarly journals Intratumoral Canine Distemper Virus Infection Inhibits Tumor Growth by Modulation of the Tumor Microenvironment in a Murine Xenograft Model of Canine Histiocytic Sarcoma

2021 ◽  
Vol 22 (7) ◽  
pp. 3578
Author(s):  
Federico Armando ◽  
Adnan Fayyad ◽  
Stefanie Arms ◽  
Yvonne Barthel ◽  
Dirk Schaudien ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Virus Infection ◽  
Tumor Growth ◽  
Canine Distemper Virus ◽  
Xenograft Model ◽  
Histiocytic Sarcoma ◽  
Oncolytic Viruses ◽  
Canine Distemper ◽  
Murine Xenograft Model ◽  
The Impact

Histiocytic sarcomas refer to highly aggressive tumors with a poor prognosis that respond poorly to conventional treatment approaches. Oncolytic viruses, which have gained significant traction as a cancer therapy in recent decades, represent a promising option for treating histiocytic sarcomas through their replication and/or by modulating the tumor microenvironment. The live attenuated canine distemper virus (CDV) vaccine strain Onderstepoort represents an attractive candidate for oncolytic viral therapy. In the present study, oncolytic virotherapy with CDV was used to investigate the impact of this virus infection on tumor cell growth through direct oncolytic effects or by virus-mediated modulation of the tumor microenvironment with special emphasis on angiogenesis, expression of selected MMPs and TIMP-1 and tumor-associated macrophages in a murine xenograft model of canine histiocytic sarcoma. Treatment of mice with xenotransplanted canine histiocytic sarcomas using CDV induced overt retardation in tumor progression accompanied by necrosis of neoplastic cells, increased numbers of intratumoral macrophages, reduced angiogenesis and modulation of the expression of MMPs and TIMP-1. The present data suggest that CDV inhibits tumor growth in a multifactorial way, including direct cell lysis and reduction of angiogenesis and modulation of MMPs and their inhibitor TIMP-1, providing further support for the concept of its role in oncolytic therapies.

Photoactive conjugated polymer/graphdiyne nanocatalyst for CO2 reduce into CO in living cells for hypoxia tumor treatment

2021 ◽  
Author(s):  
Endong Zhang ◽  
Zicheng Zuo ◽  
Wen Yu ◽  
Hao Zhao ◽  
Shengpeng Xia ◽  
...  
Keyword(s):  
Carbon Monoxide ◽  
Photodynamic Therapy ◽  
Tumor Microenvironment ◽  
Conjugated Polymer ◽  
Tumor Therapy ◽  
Living Cells ◽  
Tumor Treatment ◽  
Treatment Efficiency ◽  
Therapy Strategy ◽  
Co Gas

Carbon monoxide (CO) gas therapy has grown to be an emerging tumor therapy strategy to avoid low treatment efficiency of photodynamic therapy (PDT) caused by the hypoxia tumor microenvironment. However,...

scholarly journals Biomimetic oxygen delivery nanoparticles for enhancing photodynamic therapy in triple-negative breast cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Hanyi Fang ◽  
Yongkang Gai ◽  
Sheng Wang ◽  
Qingyao Liu ◽  
Xiao Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Photodynamic Therapy ◽  
Cancer Cell ◽  
Triple Negative Breast Cancer ◽  
Oxygen Delivery ◽  
Therapeutic Efficacy ◽  
Triple Negative ◽  
Oxygen Solubility ◽  
Post Injection

Abstract Background Triple-negative breast cancer (TNBC) is a kind of aggressive breast cancer with a high rate of metastasis, poor overall survival time, and a low response to targeted therapies. To improve the therapeutic efficacy and overcome the drug resistance of TNBC treatments, here we developed the cancer cell membrane-coated oxygen delivery nanoprobe, CCm–HSA–ICG–PFTBA, which can improve the hypoxia at tumor sites and enhance the therapeutic efficacy of the photodynamic therapy (PDT), resulting in relieving the tumor growth in TNBC xenografts. Results The size of the CCm–HSA–ICG–PFTBA was 131.3 ± 1.08 nm. The in vitro 1O2 and ROS concentrations of the CCm–HSA–ICG–PFTBA group were both significantly higher than those of the other groups (P < 0.001). In vivo fluorescence imaging revealed that the best time window was at 24 h post-injection of the CCm–HSA–ICG–PFTBA. Both in vivo 18F-FMISO PET imaging and ex vivo immunofluorescence staining results exhibited that the tumor hypoxia was significantly improved at 24 h post-injection of the CCm–HSA–ICG–PFTBA. For in vivo PDT treatment, the tumor volume and weight of the CCm–HSA–ICG–PFTBA with NIR group were both the smallest among all the groups and significantly decreased compared to the untreated group (P < 0.01). No obvious biotoxicity was observed by the injection of CCm–HSA–ICG–PFTBA till 14 days. Conclusions By using the high oxygen solubility of perfluorocarbon (PFC) and the homologous targeting ability of cancer cell membranes, CCm–HSA–ICG–PFTBA can target tumor tissues, mitigate the hypoxia of the tumor microenvironment, and enhance the PDT efficacy in TNBC xenografts. Furthermore, the HSA, ICG, and PFC are all FDA-approved materials, which render the nanoparticles highly biocompatible and enhance the potential for clinical translation in the treatment of TNBC patients.

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