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Architectonics of phage-liposome nanowebs as optimized photosensitizer vehicles for photodynamic cancer therapy.

ABSTRACT: Filamentous M13 phage can be engineered to display cancer cell-targeting or tumor-homing peptides through phage display. It would be highly desirable if the tumor-targeting phage can also carry anticancer drugs to deliver them to the cancer cells. We studied the evolution of structures of the complexes between anionic filamentous M13 phage and cationic serum-stable liposomes that encapsulate the monomeric photosensitizer zinc naphthalocyanine. At specific phage-liposome ratios, multiple phage nanofibers and liposomes are interwoven into a "nanoweb." The chemical and biological properties of the phage-liposome nanoweb were evaluated for possible application in drug delivery. This study highlights the ability of phage-liposome nanowebs to serve as efficient carriers in the transport of photosensitizers to cancer cells.

SUBMITTER: Kalarical Janardhanan S

PROVIDER: S-EPMC2937092 | biostudies-other | 2010 Sep

REPOSITORIES: biostudies-other

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Architectonics of phage-liposome nanowebs as optimized photosensitizer vehicles for photodynamic cancer therapy.

Kalarical Janardhanan Sreeram S Narayan Shoba S Abbineni Gopal G Hayhurst Andrew A Mao Chuanbin C

Molecular cancer therapeutics 20100831 9

Filamentous M13 phage can be engineered to display cancer cell-targeting or tumor-homing peptides through phage display. It would be highly desirable if the tumor-targeting phage can also carry anticancer drugs to deliver them to the cancer cells. We studied the evolution of structures of the complexes between anionic filamentous M13 phage and cationic serum-stable liposomes that encapsulate the monomeric photosensitizer zinc naphthalocyanine. At specific phage-liposome ratios, multiple phage na ...[more]

PMID: 20807781

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Project description:The noninvasive nature of photodynamic therapy (PDT) enables the preservation of organ function in cancer patients. However, PDT is impeded by hypoxia in the tumor microenvironment (TME) caused by high intracellular oxygen (O2) consumption and distorted tumor blood vessels. Therefore, increasing oxygen generation in the TME would be a promising methodology for enhancing PDT. Herein, we proposed a concept of ferroptosis-promoted PDT based on the biochemical characteristics of cellular ferroptosis, which improved the PDT efficacy significantly by producing reactive oxygen species (ROS) and supplying O2 sustainably through the Fenton reaction. In contrast to traditional strategies that increase O2 based on decomposition of limited concentration of hydrogen peroxide (H2O2), our methodology could maintain the concentration of H2O2 and O2 through the Fenton reaction. Methods: For its association with sensitivity to ferroptosis, solute carrier family 7 member 11 (SLC7A11) expression was characterized by bioinformatics analysis and immunohistochemistry of oral tongue squamous cell carcinoma (OTSCC) specimens. Afterwards, the photosensitizer chlorin e6 (Ce6) and the ferroptosis inducer erastin were self-assembled into a novel supramolecular Ce6-erastin nanodrug through hydrogen bonding and π-π stacking. Then, the obtained Ce6-erastin was extensively characterized and its anti-tumor efficacy towards OTSCC was evaluated both in vitro and in vivo. Results: SLC7A11 expression is found to be upregulated in OTSCC, which is a potential target for ferroptosis-mediated OTSCC treatment. Ce6-erastin nanoparticles exhibited low cytotoxicity to normal tissues. More significantly, The over-accumulated intracellular ROS, increased O2 concentration and inhibited SLC7A11 expression lead to enhanced toxicity to CAL-27 cells and satisfactory antitumor effects to xenograft tumour mouse model upon irradiation. Conclusion: Our ferroptosis promoted PDT approach markedly enhances anticancer actions by relieving hypoxia and promoting ROS production, thereby our work provides a new approach for overcoming hypoxia-associated resistance of PDT in cancer treatment.

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Architectonics of phage-liposome nanowebs as optimized photosensitizer vehicles for photodynamic cancer therapy.

Publications

Architectonics of phage-liposome nanowebs as optimized photosensitizer vehicles for photodynamic cancer therapy.

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