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Implantable micro-scale LED device guided photodynamic therapy to potentiate antitumor immunity with mild visible light.

ABSTRACT:

Background

Photodynamic therapy (PDT) is a promising strategy to promote antitumor immunity by inducing immunogenic cell death (ICD) in tumor cells. However, practical PDT uses an intense visible light owing to the shallow penetration depth of the light, resulting in immunosuppression at the tumor tissues.

Methods

Herein, we propose an implantable micro-scale light-emitting diode device (micro-LED) guided PDT that enables the on-demand light activation of photosensitizers deep in the body to potentiate antitumor immunity with mild visible light.

Results

The micro-LED is prepared by stacking one to four micro-scale LEDs (100 μm) on a needle-shape photonic device, which can be directly implanted into the core part of the tumor tissue. The photonic device with four LEDs efficiently elicits sufficient light output powers without thermal degradation and promotes reactive oxygen species (ROS) from a photosensitizer (verteporfin; VPF). After the intravenous injection of VPF in colon tumor-bearing mice, the tumor tissues are irradiated with optimal light intensity using an implanted micro-LED. While tumor tissues under intense visible light causes immunosuppression by severe inflammatory responses and regulatory T cell activation, mild visible light elicits potent ICD in tumor cells, which promotes dendritic cell (DC) maturation and T cell activation. The enhanced therapeutic efficacy and antitumor immunity by micro-LED guided PDT with mild visible light are assessed in colon tumor models. Finally, micro-LED guided PDT in combination with immune checkpoint blockade leads to 100% complete tumor regression and also establishes systemic immunological memory to prevent the recurrence of tumors.

Conclusion

Collectively, this study demonstrates that micro-LED guided PDT with mild visible light is a promising strategy for cancer immunotherapy.

SUBMITTER: Choi J

PROVIDER: S-EPMC9580183 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Publications

Implantable micro-scale LED device guided photodynamic therapy to potentiate antitumor immunity with mild visible light.

Choi Jiwoong J Lee Il Seong IS Lee Ju Seung JS Jeon Sangmin S Yun Wan Su WS Yang Suah S Moon Yujeong Y Kim Jinseong J Kim Jeongrae J Choy Seunghwan S Jeong Chanho C Shim Man Kyu MK Kim Tae-Il TI Kim Kwangmeyung K

Biomaterials research 20221018 1

<h4>Background</h4>Photodynamic therapy (PDT) is a promising strategy to promote antitumor immunity by inducing immunogenic cell death (ICD) in tumor cells. However, practical PDT uses an intense visible light owing to the shallow penetration depth of the light, resulting in immunosuppression at the tumor tissues.<h4>Methods</h4>Herein, we propose an implantable micro-scale light-emitting diode device (micro-LED) guided PDT that enables the on-demand light activation of photosensitizers deep in ...[more]

PMID: 36258234

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Project description:Drug-resistant bacteria threaten the health of people world-wide and cause high costs to their health systems. According to Scientific American, the number of regrettable fatalities due to the bacteria that are resistant to conventional antibiotics will sum up to 300 million until 2050 if the problem is not tackled immediately. Photodynamic Inactivation (PDI) has proven effective against microorganisms irrespective of their resistance to conventional treatment, but for the translation into clinical practice, economic, homogenous and powerful light sources holding approval as medical devices are needed. In this study we present two novel light emitting diode (LED)-based lamps (Repuls7PDI-red and Repuls7PDI-blue) tailored for application in PDI and demonstrate their photodynamic efficiency upon using either methylene blue (MB), a photoactive compound widely used in PDI, or Sodium Magnesium Chlorophyllin (CHL), a water-soluble derivative of chlorophyll, which holds approval as food additive E140, against bacteria and fungi. Gram+ Staphylococcus aureus, Gram- Escherichia coli and the yeast Candida albicans serve as model systems. Repuls7PDI-red emits a wavelength of 635 nm and an intensity of 27.6 ± 2.4 mW·cm-2 at a distance of 13.5 cm between the light source and the target, while the Repuls7PDI-blue allows an exposure at 433 nm (within the range of violet light) (6.4 ± 0.5 mW·cm-2 at 13.5 cm). Methylene blue was photoactivated with the Repuls7PDI-red at 635 nm (25.6 J·cm-2) and allows for photokilling of E. coli by more than 6 log10 steps at a concentration of 10 µM MB. Using equal parameters, more than 99.99999% of S. aureus (20 µM MB) and 99.99% of C. albicans (50 µM MB) were killed. If blue light (Repuls7PDI-blue, 433 nm, 6.6 J·cm2) is used to trigger the production of reactive oxygen species (ROS), a photoinactivation of S. aureus (5 µM CHL, CFU reduction > 7 log10) and C. albicans (>7 log10) below the detection limit is achieved. PDI based on CHL (10 µM) using red light activation reduces the number of viable S. aureus by more than 6 log10. Our data prove that both LED-based light sources are applicable for Photodynamic Inactivation. Their easy-to-use concept, high light output and well-defined wavelength might facilitate the translation of PDI into clinical practice.

Project description:BackgroundTemporary disruption of the blood-brain barrier (BBB) using pulsed ultrasound leads to the clearance of both amyloid and tau from the brain, increased neurogenesis, and mitigation of cognitive decline in pre-clinical models of Alzheimer's disease (AD) while also increasing BBB penetration of therapeutic antibodies. The goal of this pilot clinical trial was to investigate the safety and efficacy of this approach in patients with mild AD using an implantable ultrasound device.MethodsAn implantable, 1-MHz ultrasound device (SonoCloud-1) was implanted under local anesthesia in the skull (extradural) of 10 mild AD patients to target the left supra-marginal gyrus. Over 3.5 months, seven ultrasound sessions in combination with intravenous infusion of microbubbles were performed twice per month to temporarily disrupt the BBB. 18F-florbetapir and 18F-fluorodeoxyglucose positron emission tomography (PET) imaging were performed on a combined PET/MRI scanner at inclusion and at 4 and 8 months after the initiation of sonications to monitor the brain metabolism and amyloid levels along with cognitive evaluations. The evolution of cognitive and neuroimaging features was compared to that of a matched sample of control participants taken from the Alzheimer's Disease Neuroimaging Initiative (ADNI).ResultsA total of 63 BBB opening procedures were performed in nine subjects. The procedure was well-tolerated. A non-significant decrease in amyloid accumulation at 4 months of - 6.6% (SD = 7.2%) on 18F-florbetapir PET imaging in the sonicated gray matter targeted by the ultrasound transducer was observed compared to baseline in six subjects that completed treatments and who had evaluable imaging scans. No differences in the longitudinal change in the glucose metabolism were observed compared to the neighboring or contralateral regions or to the change observed in the same region in ADNI participants. No significant effect on cognition evolution was observed in comparison with the ADNI participants as expected due to the small sample size and duration of the trial.ConclusionsThese results demonstrate the safety of ultrasound-based BBB disruption and the potential of this technology to be used as a therapy for AD patients. Research of this technique in a larger clinical trial with a device designed to sonicate larger volumes of tissue and in combination with disease-modifying drugs may further enhance the effects observed.Trial registrationClinicalTrials.gov, NCT03119961.

Dataset Information

Implantable micro-scale LED device guided photodynamic therapy to potentiate antitumor immunity with mild visible light.

Background

Methods

Results

Conclusion

Publications

Implantable micro-scale LED device guided photodynamic therapy to potentiate antitumor immunity with mild visible light.

Similar Datasets

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