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Photodynamic therapy (PDT) as a treatment method has many advantages such as minimal invasiveness, repeatable dosage and low systemic toxicity. Issues with conventional PDT agents include the limited availability of endogenous oxygen and difficulty in accumulation at tumor site, which hindered the successful treatment of tumor. Herein, we developed catalase-encapsulated hyaluronic acid-based nanoparticles loaded with adamantane modified photosensitizer for enhanced PDT of solid tumor. Chlorin e6 (Ce6) as the photosensitizer was modified with adamantane to yield adamantane modified Ce6 (aCe6). The obtained nanosystem (HA-CAT@aCe6) could target overly expressed CD44 receptors on cancer cells, supplying oxygen by converting endogenous hydrogen peroxide (H2O2) to oxygen, and improving PDT efficacy upon the light irradiation. HA-CAT@aCe6 nanoparticles showed high colloidal stability and mono-dispersity in aqueous solution. The uptake and targeting property of HA-CAT@aCe6 were demonstrated by confocal microscopy and flow cytometry in MDA-MB-231 cell line possessing overly expressed CD44 receptors. The encapsulated catalase was able to decompose the endogenous H2O2 to generate O2 in situ for relieving hypoxia in cells incubated under hypoxia conditions. Cell viability assays indicated that HA-CAT@aCe6 possessed minimal cytotoxicity in the dark, while presenting high cellular toxicity under 660 nm light irradiation at normoxic condition. As a result of the catalase capability in relieving hypoxia, HA-CAT@aCe6 also exhibited high cellular cytotoxicity under hypoxia condition. In vivo experiments revealed selective tumor accumulation of HA-CAT@aCe6 in MDA-MB-231 tumor bearing nude mice. Significant tumor regression was observed after intravenous injection of HA-CAT@aCe6 under light irradiation in comparison to the control system without loading catalase. Thus, HA-CAT@aCe6 demonstrated a great potential in overcoming hypoxia for targeted PDT.
This article was published in the following journal.
Name: ACS nano
Chemo-photodynamic therapy is an attractive strategy against cancer. However, the combination of chemotherapeutic agent and photosensitizer is usually realized by physically embedding one or two agent...
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The purified component of HEMATOPORPHYRIN DERIVATIVE, it consists of a mixture of oligomeric porphyrins. It is used in photodynamic therapy (HEMATOPORPHYRIN PHOTORADIATION); to treat malignant lesions with visible light and experimentally as an antiviral agent. It is the first drug to be approved in the use of PHOTODYNAMIC THERAPY in the United States.
A complex mixture of monomeric and aggregated porphyrins used in the photodynamic therapy of tumors (HEMATOPORPHYRIN PHOTORADIATION). A purified component of this mixture is known as DIHEMATOPORPHYRIN ETHER.
A group of high molecular weight chondroitin sulfate proteoglycans that form aggregates with HYALURONIC ACID.
Materials such as COLLAGEN or HYALURONIC ACID that are injected or deposited into the DERMIS for the purpose of skin augmentation.
An integrated nano-scale approach to MEDICINE which involves concurrent diagnosis, drug delivery, therapy, and monitoring of therapeutic response.
Bladder Cancer Brain Cancer Breast Cancer Cancer Cervical Cancer Colorectal Head & Neck Cancers Hodgkin Lymphoma Leukemia Lung Cancer Melanoma Myeloma Ovarian Cancer Pancreatic Cancer ...