Functional titanium dioxide nanoparticle conjugated with phthalocyanine and folic acid as a promising photosensitizer for targeted photodynamic therapy in vitro and in vivo

Imaging-guided cancer theranostic is a promising strategy for cancer diagnostic and therapeutic. Photodynamic therapy (PDT), as an approved treatment modality, is limited by the poor solubility and dispersion of photosensitizers (PS) in biological fluids. Herein, it is demonstrated that superparamagnetic iron oxide (SPIO)-based nanoparticles (SCFs), prepared by conjugated with Chlorin e6 (Ce6) and modified with folic acid (FA) on the surface, can be used as versatile drug delivery vehicles for effective PDT. The nanoparticles are great carriers for photosensitizer Ce6 with an extremely high loading efficiency. In vitro fluorescence imaging and in vivo magnetic resonance imaging (MRI) results indicated that SCFs selectively accumulated in tumor cells. Under near-infrared laser irradiation, SCFs were confirmed to be capable of inducing low cell viability of RM-1 cells In vitro and displaying efficient tumor ablation with negligible side effects in tumor-bearing mice models.

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Folic Acid–Conjugated Pyropheophorbide a as the Photosensitizer Tested for In Vivo Targeted Photodynamic Therapy

Journal of Pharmaceutical Sciences ◽

10.1016/j.xphs.2017.02.019 ◽

2017 ◽

Vol 106 (6) ◽

pp. 1482-1489 ◽

Cited By ~ 6

Author(s):

Jin Wang ◽

Qian Liu ◽

Yuting Zhang ◽

Huan Shi ◽

Hui Liu ◽

...

Keyword(s):

Photodynamic Therapy ◽

Folic Acid ◽

Pyropheophorbide A ◽

Targeted Photodynamic Therapy

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Targeted Photodynamic Therapy and Photochemical Internalization of Human Head and Neck Cancer: a preclinical study in vitro and in vivo

10.33612/diss.167799500 ◽

2021 ◽

Author(s):

◽

Wei Peng

Keyword(s):

Head And Neck Cancer ◽

Photodynamic Therapy ◽

Head And Neck ◽

Neck Cancer ◽

Human Head ◽

Preclinical Study ◽

Photochemical Internalization ◽

Targeted Photodynamic Therapy

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Targeted photodynamic therapy selectively kills activated fibroblasts in experimental arthritis

Rheumatology ◽

10.1093/rheumatology/keaa295 ◽

2020 ◽

Vol 59 (12) ◽

pp. 3952-3960 ◽

Cited By ~ 1

Author(s):

Daphne N Dorst ◽

Mark Rijpkema ◽

Marti Boss ◽

Birgitte Walgreen ◽

Monique M A Helsen ◽

...

Keyword(s):

Photodynamic Therapy ◽

Therapeutic Potential ◽

Ex Vivo ◽

Synovial Fibroblasts ◽

Knee Joints ◽

Specific Cell ◽

Collagen Induced Arthritis ◽

Targeted Photodynamic Therapy

Abstract Objective In RA, synovial fibroblasts become activated. These cells express fibroblast activation protein (FAP) and contribute to the pathogenesis by producing cytokines, chemokines and proteases. Selective depletion in inflamed joints could therefore constitute a viable treatment option. To this end, we developed and tested a new therapeutic strategy based on the selective destruction of FAP-positive cells by targeted photodynamic therapy (tPDT) using the anti-FAP antibody 28H1 coupled to the photosensitizer IRDye700DX. Methods After conjugation of IRDye700DX to 28H1, the immunoreactive binding and specificity of the conjugate were determined. Subsequently, tPDT efficiency was established in vitro using a 3T3 cell line stably transfected with FAP. The biodistribution of [111In]In-DTPA-28H1 with and without IRDye700DX was assessed in healthy C57BL/6N mice and in C57BL/6N mice with antigen-induced arthritis. The potential of FAP-tPDT to induce targeted damage was determined ex vivo by treating knee joints from C57BL/6N mice with antigen-induced arthritis 24 h after injection of the conjugate. Finally, the effect of FAP-tPDT on arthritis development was determined in mice with collagen-induced arthritis. Results 28H1-700DX was able to efficiently induce FAP-specific cell death in vitro. Accumulation of the anti-FAP antibody in arthritic knee joints was not affected by conjugation with the photosensitizer. Arthritis development was moderately delayed in mice with collagen-induced arthritis after FAP-tPDT. Conclusion Here we demonstrate the feasibility of tPDT to selectively target and kill FAP-positive fibroblasts in vitro and modulate arthritis in vivo using a mouse model of RA. This approach may have therapeutic potential in (refractory) arthritis.

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Effective treatment of chemoresistant breast cancer in vitro and in vivo by a factor VII-targeted photodynamic therapy

British Journal of Cancer ◽

10.1038/bjc.2011.88 ◽

2011 ◽

Vol 104 (9) ◽

pp. 1401-1409 ◽

Cited By ~ 27

Author(s):

J Duanmu ◽

J Cheng ◽

J Xu ◽

C J Booth ◽

Z Hu

Keyword(s):

Breast Cancer ◽

Photodynamic Therapy ◽

Effective Treatment ◽

Factor Vii ◽

Targeted Photodynamic Therapy

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A monomeric photosensitizer for targeted cancer therapy

Chemical Communications ◽

10.1039/c4cc07628a ◽

2014 ◽

Vol 50 (95) ◽

pp. 14983-14986 ◽

Cited By ~ 9

Author(s):

Ruizheng Liang ◽

Lina Ma ◽

Lele Zhang ◽

Chunyang Li ◽

Wendi Liu ◽

...

Keyword(s):

Photodynamic Therapy ◽

Folic Acid ◽

Cancer Therapy ◽

Zinc Phthalocyanine ◽

Targeted Cancer Therapy

A targeted photosensitizer used in photodynamic therapy (PDT) was fabricated by incorporation of zinc phthalocyanine (ZnPc) and folic acid (FA) into polyvinylpyrrolidone (PVP) micelles, which exhibits excellent anticancer performance revealed by both in vitro studies and in vivo tests.

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A folic acid conjugated polyethylenimine-modified PEGylated nanographene loaded photosensitizer: photodynamic therapy and toxicity studies in vitro and in vivo

Journal of Materials Chemistry B ◽

10.1039/c6tb00108d ◽

2016 ◽

Vol 4 (12) ◽

pp. 2190-2198 ◽

Cited By ~ 10

Author(s):

Yi-Ping Zeng ◽

Sheng-Lin Luo ◽

Zhang-You Yang ◽

Jia-Wei Huang ◽

Hong Li ◽

...

Keyword(s):

Photodynamic Therapy ◽

Folic Acid ◽

Delivery System ◽

Tumor Targeting ◽

Therapy Efficacy ◽

Toxicity Studies ◽

Targeting Delivery

A novel nanographene-based tumor-targeting delivery system has high photodynamic therapy efficacy with no obvious toxicity and could potentially be utilized in biomedicine.

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EpCAM-Binding DARPins for Targeted Photodynamic Therapy of Ovarian Cancer

Cancers ◽

10.3390/cancers12071762 ◽

2020 ◽

Vol 12 (7) ◽

pp. 1762

Author(s):

Dirk van den Brand ◽

Sanne A. M. van Lith ◽

Jelske M. de Jong ◽

Mark A. J. Gorris ◽

Valentina Palacio-Castañeda ◽

...

Keyword(s):

Ovarian Cancer ◽

Photodynamic Therapy ◽

Specific Binding ◽

Abdominal Cavity ◽

Therapeutic Modality ◽

Cancer Models ◽

Ankyrin Repeat Proteins ◽

Targeted Photodynamic Therapy

Ovarian cancer is the most lethal gynecological malignancy due to late detection associated with dissemination throughout the abdominal cavity. Targeted photodynamic therapy (tPDT) aimed at epithelial cell adhesion molecule (EpCAM), overexpressed in over 90% of ovarian cancer metastatic lesions, is a promising novel therapeutic modality. Here, we tested the specificity and activity of conjugates of EpCAM-directed designed ankyrin repeat proteins (DARPins) with the photosensitizer IRDye 700DX in in vitro and in vivo ovarian cancer models. EpCAM-binding DARPins (Ec1: Kd = 68 pM; Ac2: Kd = 130 nM) and a control DARPin were site-specifically functionalized with fluorophores or IRDye 700DX. Conjugation of anti-EpCAM DARPins with fluorophores maintained EpCAM-specific binding in cell lines and patient-derived ovarian cancer explants. Penetration of DARPin Ec1 into tumor spheroids was slower than that of Ac2, indicative of a binding site barrier effect for Ec1. DARPin-IRDye 700DX conjugates killed EpCAM-expressing cells in a highly specific and illumination-dependent fashion in 2D and 3D cultures. Furthermore, they effectively homed to EpCAM-expressing subcutaneous OV90 xenografts in mice. In conclusion, the high activity and specificity observed in preclinical ovarian cancer models, combined with a high specificity in patient material, warrant a further investigation of EpCAM-targeted PDT for ovarian cancer.

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