Dark-Bubble Phenomenon in Biophysics

Cancer remains a formidable health challenge globally, ranking as the second leading cause of death in the United States. Traditional cancer treatments have long relied on radiation therapy (RT), either as a standalone treatment or in conjunction with chemotherapy, to reduce tumor burden by destroying cancer cells. However, the crux of maximizing the efficacy of RT lies in the accurate pre-planning of the radiation dose (RD). This is crucial not only to ensure the destruction of cancer cells but also to prevent damage to adjacent healthy tissues or the induction of secondary carcinogenesis. Therefore, establishing the precise threshold RD is of paramount importance for optimizing RT outcomes.

Addressing this critical need, our research introduces an innovative technology that leverages laser trapping (LT) combinatory techniques to analyze irreparable DNA damage simultaneously. This breakthrough stems from a novel LT technique developed in our laboratory, which allows for the precise measurement of ionization RD at the cellular level based on charge. The LT optical technique facilitates the manipulation of dielectric particles ranging from nanometers to microns, encompassing both living and non-living molecules. Through this method, our team has successfully demonstrated the feasibility of determining the minimum RD necessary to eradicate cancer cells at a cellular level.

This novel approach promises greater accuracy than existing standard methods and is poised to revolutionize RT for cancer treatment. It also addresses the challenge posed by combinatorial treatments, where many cancer drugs exhibit radiosensitivity, potentially altering the effective dosage for cells. Our prior research on the effects of oligostilbenes on cellular responses to radiation underscores the potential of these compounds in enhancing antitumor activity while minimizing damage to normal tissues.

The current proposal seeks to extend this innovative method to animal models and explore its application in combinatorial therapy settings, particularly in combined chemoradiotherapy. This is driven by the need to improve RD determination in antitumor activity and reduce toxicity in normal tissues. Specifically, we aim to:

• Aim 1: Determine the radiation dose for various cancer cells in different patients treated with oligostilbenes. By focusing on cancer and epithelial cells from human breast and lung, this screening aims to establish the effectiveness of oligostilbenes in enhancing radiation sensitivity in cancer cells and protecting normal tissues from radiation-induced damage. We will also assess the combined effect of oligostilbenes with various cancer drugs on different cancer lines.
• Aim 2: Evaluate the effectiveness of certain cancer drugs in increasing the radio-sensitivity of tumor cells while reducing radiation toxicity in normal cells, using a mouse model. This involves using an integrated screening platform to examine the combination of cancer treatment drugs and RT.

Sub-Project: Electromagnetic Dynamics and Characterization of the 'Dark-bubble' Phenomenon in Cancer Cell-Magnetic Bead Interactions

Background: The interaction of dielectric materials with electromagnetic fields is pivotal for the development of advanced technologies. While considerable research has focused on static fields, the dynamics within oscillating electromagnetic environments are less understood. This sub-project aims to explore these dynamics, specifically through the lens of a novel "Dark-bubble" phenomenon observed in cancer cell-magnetic bead interactions within a laser trapping apparatus. This phenomenon, characterized by the formation and subsequent collapse of a "Dark-bubble" that emits intense radiation, akin to a micro-scale star, represents a groundbreaking discovery in biophysics.

Specific Aims/Hypothesis:

1. Investigate the mechanisms behind the "Dark-bubble" phenomenon, including its formation, expansion, and collapse.
2. Model the entrapment and release of electromagnetic energy within this context, utilizing the framework of Electromagnetic Characterization and Dynamics of Concentric Dielectric Spheres in Oscillating Fields.
3. Determine the quantitative relationship between the incident laser power and the intensity of the radiation emitted upon the "Dark-bubble" collapse.

The hypothesis posits that the "Dark-bubble" phenomenon results from complex interactions between electromagnetic fields and the dielectric properties of cancer cells and magnetic beads. These interactions can be effectively modeled by extending the theory of concentric dielectric spheres in oscillating electromagnetic fields.

This project, along with its sub-project, stands to offer valuable insights into the effectiveness of RT and lay the groundwork for the development of more accurate RT treatment plans, whether used alone or in combination with chemotherapeutics or oligostilbenes. By delving into the electromagnetic dynamics and characterization of the "Dark-bubble" phenomenon, we aim to further enhance the precision of cancer treatments, potentially revolutionizing targeted therapy approaches and biophysical research.