Photoacoustic nanodroplets for oxygen enhanced photodynamic therapy of cancer

Marvin Xavierselvan; Jason Cook; Jeanne Duong; Nashielli Diaz; Kimberly Homan; Srivalleesha Mallidi

doi:10.1016/j.pacs.2021.100306

Photoacoustic nanodroplets for oxygen enhanced photodynamic therapy of cancer

Photoacoustics. 2021 Sep 27:25:100306. doi: 10.1016/j.pacs.2021.100306. eCollection 2022 Mar.

Authors

Marvin Xavierselvan¹, Jason Cook², Jeanne Duong¹, Nashielli Diaz¹, Kimberly Homan², Srivalleesha Mallidi^{1

3}

Affiliations

¹ Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA.
² NanoHybrids Inc., Austin, TX 78744, USA.
³ Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA.

Abstract

Photodynamic therapy (PDT) is a well-known cancer therapy that utilizes light to excite a photosensitizer and generate cytotoxic reactive oxygen species (ROS). The efficacy of PDT primarily depends on the photosensitizer and oxygen concentration in the tumor. Hypoxia in solid tumors promotes treatment resistance, resulting in poor PDT outcomes. Hence, there is a need to combat hypoxia while delivering sufficient photosensitizer to the tumor for ROS generation. Here we showcase our unique theranostic perfluorocarbon nanodroplets as a triple agent carrier for oxygen, photosensitizer, and indocyanine green that enables light triggered spatiotemporal delivery of oxygen to the tumors. We evaluated the characteristics of the nanodroplets and validated their ability to deliver oxygen via photoacoustic monitoring of blood oxygen saturation and subsequent PDT efficacy in a murine subcutaneous tumor model. The imaging results were validated with an oxygen sensing probe, which showed a 9.1 fold increase in oxygen content inside the tumor, following systemic administration of the nanodroplets. These results were also confirmed with immunofluorescence. In vivo studies showed that nanodroplets held higher rates of treatment efficacy than a clinically available benzoporphyrin derivative formulation. Histological analysis showed higher necrotic area within the tumor with perfluoropentane nanodroplets. Overall, the photoacoustic nanodroplets can significantly enhance image-guided PDT and has demonstrated substantial potential as a valid theranostic option for patient-specific photodynamic therapy-based treatments.

Keywords: 1O2, singlet oxygen; BPD, benzoporphyrin derivative; DLS, dynamic light scattering; DPPC, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine; DSPE-mPEG, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000]; H&E, hematoxylin and eosin; HbT, total hemoglobin; Hypoxia; ICG, indocyanine green; IF, immunofluorescence; Image guided PDT; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; NIR, near infrared radiation; PA, photoacoustic; PBS, phosphate buffered saline; PDT, photodynamic therapy; PFC, perfluorocarbon; PFP, perfluoropentane; PS, photosensitizer; Perfluorocarbon nanodroplets; Photoacoustic imaging; Photodynamic therapy; ROS, reactive oxygen species; SOSG, singlet oxygen sensor green; StO2, oxygen saturation; TBAI, tertbutylammonium iodide; pO2, partial pressure of oxygen.