Targeting Borrelia burgdorferi HtpG with a berserker molecule, a strategy for anti-microbial development

Published in: Cell Chemical Biology Authors: Dave L. Carlson, Mark Kowalewski, Khaldon Bodoor, Matthew R. Redinbo, Neil Spector, Timothy A.J. Haystead Duke UniversityPublished in: Cell Chemical Biology Authors: Dave L. Carlson, Mark Kowalewski, Khaldon Bodoor, Matthew R. Redinbo, Neil Spector, Timothy A.J. Haystead Duke University Conventional antimicrobial discovery relies on targeting essential enzymes in pathogenic organisms, contributing to a paucity of new antibiotics to address resistant strains. Here, by targeting a non-essential enzyme, Borrelia burgdorferi HtpG, to deliver lethal payloads, we expand what can be considered druggable within any pathogen. We synthesized HS-291, an HtpG inhibitor tethered to the photoactive toxin verteporfin. Reactive oxygen species, generated by light, enables Continue reading →

Photoimmunotechnology as a powerful biological tool for molecular-based elimination of target cells and microbes, including bacteria, fungi and viruses

Published in: Nature Protocols Authors: Tadayuki Iwase, Kimihiro Ito, Takashi Nishimura, Kei Miyakawa, Akihide Ryo, Hisataka Kobayashi, Makoto Mitsunaga The Jikei University School of Medicine  Published in: Nature Protocols Authors: Tadayuki Iwase, Kimihiro Ito, Takashi Nishimura, Kei Miyakawa, Akihide Ryo, Hisataka Kobayashi, Makoto Mitsunaga The Jikei University School of Medicine Microbial pathogens, including bacteria, fungi and viruses, can develop resistance to clinically used drugs; therefore, finding new therapeutic agents is an ongoing challenge. Recently, we reported the photoimmuno-antimicrobial strategy (PIAS), a type of photoimmunotechnology, that enables molecularly targeted elimination of a wide range of microbes, including the viral pathogen severe acute respiratory syndrome coronavirus 2 and the multidrug-resistant bacterial pathogen Continue reading →

Fluorescence-guided photoimmunotherapy using targeted nanotechnology and ML7710 to manage peritoneal carcinomatosis

Published in: Science Advances Authors: Barry J. Liang(1,2), Sumiao Pang(1), Robert Perttilä(3), Chen-Hua Ma(1), Payal Srivastava(1), Brandon Gaitan(1), Aaron J. Sorrin (1), Nada Fadul(1), Zoe Ylöniemi(3), Dana M. Roque(4,5), Tayyaba Hasan(6), Petteri Uusimaa(3), Huang-Chiao Huang(1,4*) (1) Fischell Department of Bioengineering, University of Maryland (2) Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health (3) Modulight Corp., Finland (4) Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine (5) Department of Obstetrics, Gynecology and Reproductive Sciences, University Continue reading →Published in: Science Advances Authors: Barry J. Liang(1,2), Sumiao Pang(1), Robert Perttilä(3), Chen-Hua Ma(1), Payal Srivastava(1), Brandon Gaitan(1), Aaron J. Sorrin (1), Nada Fadul(1), Zoe Ylöniemi(3), Dana M. Roque(4,5), Tayyaba Hasan(6), Petteri Uusimaa(3), Huang-Chiao Huang(1,4*) (1) Fischell Department of Bioengineering, University of Maryland (2) Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health (3) Modulight Corp., Finland (4) Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine (5) Department of Obstetrics, Gynecology and Reproductive Sciences, University Continue reading →

Photodynamic Therapy of an Abdominal Abscess at the Time of Percutaneous Drainage

Published in: Cardiovascular and Interventional Radiology Authors: Timothy M. Baran, Ashwani Kumar Sharma    Published in: Cardiovascular and Interventional Radiology Authors: Timothy M. Baran, Ashwani Kumar Sharma   This article presents a successful case study from an ongoing Phase 1 clinical trial where methylene blue together with ML7710 is used to eradicate bacteria and biofilm in the treatment of persistent abscesses. The potential of Photodynamic Therapy (PDT) is explored as an adjunct treatment for recurrent or challenging-to-manage abdominal abscesses during percutaneous drainage procedures. Despite advancements in abscess drainage techniques and antibiotics, some cases exhibit low response rates and recurrences, Continue reading →

Intratumoral interleukin-15 improves efficacy of near-infrared photoimmunotherapy

Published in: Molecular Cancer Therapeutics Authors: Hiroshi Fukushima, Aki Furusawa, Takuya Kato, Hiroaki Wakiyama, Seiichiro Takao, Shuhei Okuyama, Peter L. Choyke, Hisataka Kobayashi    Published in: Molecular Cancer Therapeutics Authors: Hiroshi Fukushima, Aki Furusawa, Takuya Kato, Hiroaki Wakiyama, Seiichiro Takao, Shuhei Okuyama, Peter L. Choyke, Hisataka Kobayashi   Interleukin 15 (IL-15) is inducer of differentiation and proliferation of CD8+ T cells and NK cells and thus promising candidate for cancer immunotherapy. This study showed therapeutic efficacy increase in vivo when IL15 was combined with cancer cell-targeted photoimmunotherapy using ML7710 laser system. Intratumoral injection of IL-15 was more effective than intraperitoneal in suppressing tumor growth and inducing intratumoral immune responses, Continue reading →

Transient fluid flow improves photoimmunoconjugate delivery and photoimmunotherapy efficacy

Published in: iScience Authors: Aaron J. Sorrin, Keri Zhou, Katherine May, Cindy Liu, Kathryn McNaughton, Idrisa Rahman, Barry J. Liang, Imran Rizvi, Dana M. Roque, Huang-Chiao Huang    Published in: iScience Authors: Aaron J. Sorrin, Keri Zhou, Katherine May, Cindy Liu, Kathryn McNaughton, Idrisa Rahman, Barry J. Liang, Imran Rizvi, Dana M. Roque, Huang-Chiao Huang   The study showed that fluid flow induced shear stress increased the photocytotoxicity of different photosensitizers tested (BPD, PIC, PIC-coated liposome) against ovarian cancer cells. The cellular delivery of photosensitizers doubled compared to static conditions. Modulight laser was used for PDT activation together with photosensitizer(s). Circulating drugs in the peritoneal cavity is an effective strategy for advanced ovarian Continue reading →

Immune checkpoint inhibition combined with targeted therapy using a novel virus‑like drug conjugate induces complete responses in a murine model of local and distant tumors

Published in: Cancer Immunology, Immunotherapy Authors: Ruben V. Huis in ‘t Veld, Sen Ma, Rhonda C. Kines, Anneli Savinainen, Cadmus Rich, Ferry Ossendorp, Martine J. Jager    Published in: Cancer Immunology, Immunotherapy Authors: Ruben V. Huis in ‘t Veld, Sen Ma, Rhonda C. Kines, Anneli Savinainen, Cadmus Rich, Ferry Ossendorp, Martine J. Jager   AU-011 combination with immune checkpoint inhibitors (ICI) was studied in murine models. This has potential to improve treatment efficacy against metastatic tumors by abscopal immune effects. ICI was shown to increase AU-011 efficacy and also result in abscopal effect and induced complete responses in 75% of animals. ML6700 was used as illumination source for PDT. Metastases remain the Continue reading →

Fluorescence-guided, targeted photochemotherapy of peritoneal carcinomatosis

Presented in: SPIE BIOS 2023 Authors: Barry J. Liang, Robert Perttilä, Sumiao Pang, Chen-Hua Ma, Payal Srivastava, Brandon Gaitan, Aaron J. Sorrin, Zoe Ylöniemi, Dana Roque, Tayyaba Hasan, Petteri Uusimaa, Huang-Chiao Huang    Presented in: SPIE BIOS 2023 Authors: Barry J. Liang, Robert Perttilä, Sumiao Pang, Chen-Hua Ma, Payal Srivastava, Brandon Gaitan, Aaron J. Sorrin, Zoe Ylöniemi, Dana Roque, Tayyaba Hasan, Petteri Uusimaa, Huang-Chiao Huang   Management of peritoneally metastatic cancer is a major clinical challenge. Peritoneal carcinomatosis is observed in 50% of colorectal cancer patients and >75% of ovarian cancer patients at the time of diagnosis. Selected patients based on age, comorbidities, and extent of the metastatic disease, will undergo complete cytoreductive surgery to remove the visible Continue reading →

Novel ophthalmic laser system paired with focal electroretinography for subthreshold laser therapy of DME

Presented in: SPIE BIOS 2023 Authors: Jukka-Pekka Alanko, Eero Koivumäki, Laura Vesala, Johannes Kivelä, Zoe Ylöniemi, Petteri Uusimaa, Ossi Kaikkonen, Teemu Turunen, Jaakko Nieminen, Jani Tirronen    Presented in: SPIE BIOS 2023 Authors: Jukka-Pekka Alanko, Eero Koivumäki, Laura Vesala, Johannes Kivelä, Zoe Ylöniemi, Petteri Uusimaa, Ossi Kaikkonen, Teemu Turunen, Jaakko Nieminen, Jani Tirronen   In the field of ophthalmic treatments, subthreshold laser therapy (SLT) has shown promise in addressing retinal diseases like diabetic macular edema (DME) and age-related macular degeneration (AMD). However, the precise control of therapeutic temperatures is challenging due to variations in individual eye characteristics. Modulight and Maculaser have addressed this issue with their innovative ML6710i device. This device utilizes a combination of laser beams to achieve precise thermal Continue reading →

Output beam engineering with 2-step ridge etching

Presented in: SPIE OPTO 2023 Authors: Riina Ulkuniemi, Ville Vilokkinen, Petri Melanen, Petteri Uusimaa    Presented in: SPIE OPTO 2023 Authors: Riina Ulkuniemi, Ville Vilokkinen, Petri Melanen, Petteri Uusimaa   Silicon photonics offers platforms to build mass-producible optical circuits. Extremely small optical components are required for this purpose, so fiber coupled systems are an order of magnitude too large. In order to successfully integrate laser source to the circuits, output beam properties have to be controlled and desired for the purpose. When fabricating single-mode ridge waveguide (RWG) laser diodes, ridge width has to be narrow enough for ensuring single-mode operation. Continue reading →