ABSTRACT
Developing a cancer theranostic nanoplatform with diagnosis and treatment capabilities to effectively treat tumors and reduce side effects is of great significance. Herein, we present a drug delivery strategy for photosensitizers based on a new liquid metal nanoplatform that leverages the tumor microenvironment to achieve photodynamic therapeutic effects in pancreatic cancer. Eutectic gallium indium (EGaIn) nanoparticles were successfully conjugated with a water-soluble cancer targeting ligand, hyaluronic acid, and a photosensitizer, benzoporphyrin derivative, creating EGaIn nanoparticles (EGaPs) via a simple green sonication method. The prepared sphere-shaped EGaPs, with a core-shell structure, presented high biocompatibility and stability. EGaPs had greater cellular uptake, manifested targeting competence, and generated significantly higher intracellular ROS. Further, near-infrared light activation of EGaPs demonstrated their potential to effectively eliminate cancer cells due to their single oxygen generation capability. Finally, from in vivo studies, EGaPs caused tumor regression and resulted in 2.3-fold higher necrosis than the control, therefore making a good vehicle for photodynamic therapy. The overall results highlight that EGaPs provide a new way to assemble liquid metal nanomaterials with different ligands for enhanced cancer therapy.
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.
