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New study uses light-activated proteins to fight cancer

An exciting study outlining the development of a new tool for photodynamic therapy (PDT), a selective and minimally invasive cancer treatment, has been published by SV Research Scholar Awardee Dr Dennis Diaz and SV member Dr Andrew Care.

Titled “Bioengineering a Light-Responsive Encapsulin Nanoreactor: A Potential Tool for In Vitro Photodynamic Therapy,” the study was recently published in ACS Applied Materials & Interfaces, a leading journal in the field of nanoscience, and gives a glimpse into how naturally-occurring proteins can be re-programmed to treat cancer.

In a world first, the Care Research Group demonstrated the use of modified protein nanocompartments, called encapsulins, for the successful delivery of a light-activated therapeutic protein that induces tumour cell death.

“By creatively combining the fields of synthetic biology and nanomedicine, we are able to take proteins away from their ‘everyday jobs’ and reprogram them for non-natural applications, like cancer therapy,” Group Leader Dr Care says. “Here, we’ve taken tiny protein nanocompartments that naturally serve as organelles inside bacteria and developed them into biologically-derived tools for PDT.”

To kill tumour cells, first-author Dr Diaz explains, PDT relies on photosensitising agents. When these are triggered by light, they start converting the normal oxygen inside cells into a toxic form of oxygen called ROS (reactive oxygen species). “In this study, we engineered protein nanocompartments to encapsulate photosensitising proteins and deliver them into tumour cells. When we then hit the nanocompartments with light, their protein cargo transformed normal oxygen within the cells into toxic ROS, which killed the tumour cells,” she says.

According to the team, “this technology has significant potential in the personalised treatment of cancers, not only as tool for PDT, but also as a customisable delivery platform for a wide range of therapeutic cargos.”

Dr Diaz and Dr Care talked about the potential of protein-based nanoparticles on Vitalcast two years ago, when they were at the outset of the research journey that led to this publication – listen to the episode here.

Image: A light-activatable ROS-generating encapsulin nanocompartment for in vitro photodynamic therapy (PDT). (a) Diagram showing the cellular delivery, activation and phototoxic effect of encapsulin nanocompartments (Enc) loaded with mini-Singlet Oxygen Generator (Enc-mSOG). Photosensitizing Enc-mSOG enters tumor cells via endocytosis. Upon photoexcitation with blue light, internalized Enc-mSOG converts intracellular O2 into cytotoxic reactive oxygen species (ROS) that induces tumor cell death. (b) Confocal microscopy showing the internalization of fluorescent-labelled Enc (green) by A549 lung cancer cells. (c) Live-cell microscopy of a ROS-sensor (pink) in live A549 cells pre-incubated with Enc or Enc-mSOG and then non-irradiated (Dark) or irradiated with a blue laser (Light). (d) Intracellular ROS levels inside live A549 cells after each treatment; measurements given as normalized integrated density (NI). (e) Cytotoxicity: A549 viability after incubation without (control) or with Enc or Enc-mSOG for different time periods in the dark. Cell viability subsequently determined by MTT assay. (f) Phototoxicity (i.e. in vitro PDT): A549 viability after incubation without (control) or with Enc or Enc-mSOG for different durations in the dark, followed by activation with blue laser light. Cell viability later quantified via MTT assay. Scale bars = 25 µm. Adapted from Diaz et al. ACS Appl Mater Inter 2021 13 (7), 7977-7986.

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