Delivering therapeutic drug molecules to the target site and releasing the cargo site-specifically is of major interest in biomedicine. To carry and release drugs to specific target tissues, different nanotechnology approaches have been utilized. These include light-sensitive liposomal carriers, which have been engineered to release cargo from their aqueous cores when illuminated by certain wavelengths of laser light. To study drug release parameters in vitro, Modulight has designed and automated biomedical illumination system ML8500. ML8500 can be tailored to house up to eight Modulight semiconductor lasers ranging from 400nm-2000nm selected based on the optical properties of dyes and molecules of interest. The illumination system can be configured for different well plate types and includes environmental control of temperature and CO2 to provide stable conditions for the studied cell types. Utilizing the ML8500 illumination system, the safety of laser light illumination for the liposomal drug delivery was investigated in retinal pigment epithelial (ARPE-19) cell line.
There is a demand for a robust and flexible illumination and screening instrument for preclinical light-sensitive drug development and optogenetic research. While there is a great selection of different types of commercial plate readers available on the market, these instruments do not provide enough versatility for high-throughput illumination experiments. In addition, plate readers typically utilize xenon flash lamps or LEDs for sample analysis, which have wider spectral output and lower excitation powers compared to lasers. To answer this unmet need, we have developed an automated, laser-based well-plate illuminator, the ML8500. It enables flexible setup of illumination parameters like wavelength, light irradiance and fluence well-by-well within a single experiment. The fluorescence monitoring possibility expands the applicability beyond sample illumination to support various fluorescence applications. The built-in incubator minimizes unspecific cellular stress and ensures consistent data even during long measurement cycles. The system is also Cloud-connected, supporting data collection and analysis, and enabling machine learning and AI based biomedical research in the future. The ML8500 can be a useful tool for many biomedical fields such as optogenetics, where the activation of light-responsive opsins and simultaneous fluorescence monitoring of sensor proteins enables spatiotemporally controlled, all-optical electrophysiology. Independent of the field of use, the ML8500 can reduce the cost of experimental labor while increasing the reproducibility and data throughput of experiments. In this presentation, we describe the key features of the ML8500, how it is operated, proof-of-concept testing results as well as present some application areas where the ML8500 is especially useful.
Fighting cancer involves more and more combination of modalities and drugs to maximize the long-term tumor resistance and cure. The rationale for combination therapy is to use treatment modalities or drug combinations that work by different mechanisms, decreasing the likelihood that resistant cancer cells will develop. The combination of light induced therapy like photodynamic therapy (PDT) and chemotherapy has the potential to overcome the limitations traditionally associated with light-based therapies and simultaneously limit the well-known adverse effects of chemotherapy by controlling local release and dose. Modulight ML7710i medical laser systems have not only been shown to unleash the cytotoxic potential of different photochemotherapeutic compounds but also to effectively monitor the drug release process providing clinicians real-time information on treatment progress and preliminary projections on treatment outcome. In vitro and in vivo experiments suggest that Modulight ML7710i lasers are capable of inducing drug release from liposomes with different mechanisms depending on the nano-construct and laser wavelength. Near infrared wavelengths such as 808 nm are capable of disturbing liposomal bilayer upon light energy conversion to heat by dyes like indocyanine green.1 Red wavelengths such as 665 nm in turn can induce photodynamic effect also causing drug release from hydrophobic core of the liposome.2 Modulight ML7710i medical lasers are being validated for both use-cases and also for use with other dyes. The only limitation in using treatment monitoring capability is that the chemotherapeutic must have fluorescent potential. Modulight medical lasers can host multiple wavelengths within one system so that the drug release and the excitation can happen with different wavelengths if required.
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