Multi-Lens Arrays (MLA)-Assisted Photothermal Effects for Enhanced Fractional Cancer Treatment: Computational and Experimental Validations

SIMPLE SUMMARY: Colorectal cancer is one of the most common cancers and the third leading cause of cancer-related deaths in the United States. As a non- or minimally invasive cancer treatment, photothermal therapy (PTT) has been widely used to generate irreversible thermal injuries in tumors. However, conventional PTT employs an end-firing flat fiber to deliver laser energy, leading to the incomplete removal of tumor tissues due to an uneven beam distribution over the tumor surface. Multi-lens arrays (MLA) generate multiple micro-beams to uniformly distribute laser energy on the tissue surface. Therefore, the application of MLA for PTT in cancer affords a spatially enhanced distribution of micro-beams and laser-induced temperature in the tumor. The purpose of the current study is to computationally and experimentally demonstrate the therapeutic benefits of MLA-assisted fractional PTT on colorectal cancer, in comparison to flat fiber-based PTT. ABSTRACT: Conventional photothermal therapy (PTT) for cancer typically employs an end-firing flat fiber (Flat) to deliver laser energy, leading to the incomplete treatment of target cells due to a Gaussian-shaped non-uniform beam profile. The purpose of the current study is to evaluate the feasibility of multi-lens arrays (MLA) for enhanced PTT by delivering laser light in a fractional micro-beam pattern. Computational and experimental evaluations compare the photothermal responses of gelatin phantoms and aqueous dye solutions to irradiations with Flat and MLA. In vivo colon cancer models have been developed to validate the therapeutic capacity of MLA-assisted irradiation. MLA yields 1.6-fold wider and 1.9-fold deeper temperature development in the gelatin phantom than Flat, and temperature monitoring identified the optimal treatment condition at an irradiance of 2 W/cm(2) for 180 s. In vivo tests showed that the MLA group was accompanied by complete tumor eradication, whereas the Flat group yielded incomplete removal and significant tumor regrowth 14 days after PTT. The proposed MLA-assisted PTT spatially augments photothermal effects with the fractional micro-beams on the tumor and helps achieve complete tumor removal without recurrence. Further investigations are expected to optimize treatment conditions with various wavelengths and photosensitizers to warrant treatment efficacy and safety for clinical translation.