A photothermal driven chemotherapy for the treatment of metastatic melanoma

Abstract

Solid tumors are abnormal mass of tissue, which affects the organs based on its malignancy and leads to the dysfunction of the affected organs. The major problem associated with treatment of solid tumors is delivering anticancer therapeutics to the deepest layers/core of the solid tumor. Deposition of excessive extracellular matrix (ECM) hinders the therapeutics to travel towards the core of the tumor. Therefore, conventional anticancer therapeutics can only reduce the tumor size and that also for a limited duration, and tumor recurrence occurs once the therapy is discontinued. Additionally, by the time the cancer is diagnosed, the cancer cells already started affecting the major organs of the body such as lung, liver, spleen, kidney, and brain, due to their ability to metastasize and lung is the primary site for them to be infiltrated. To facilitate the anticancer therapeutics to penetrate the deeper layers of tumor, and to provide concurrent treatment of both the solid tumor and metastasis, we have designed and developed a Bimodal Light Assisted Skin Tumor and Metastasis Treatment (BLAST), which is a combination of photothermal and chemotherapeutic moieties. The BLAST is composed of 2D boron nitride (BN) nanosheet with adsorbed molecules of BCL-2 inhibitor, Navitoclax (NAVI) on its surface, that can breakdown excessive ECM network and thereby facilitate dissociation of the solid tumor. The developed BLAST was evaluated for its ability to penetrate solid tumors using 3D spheroids for the uptake, cytotoxicity, growth inhibition, reactive oxygen species (ROS) detection, penetration, and downregulation of proteins upon laser irradiation. The in vivo therapeutic studies on a skin cancer mice model revealed that the BLAST with and without laser were able to penetrate the solid tumor, reduce tumor volume in mice, dissociate the protein network, and prevent lung metastasis as confirmed by immunohistochemistry and western blot analysis. Post analysis of serum and blood components revealed the safety and efficacy of BLAST in mice. Hence, the developed BLAST holds strong promise in solid tumor treatment and metastasis prevention simultaneously.

Keywords: 2D nanomaterials; Boron nitride; Photothermal; Solid tumor; Tumor microenvironment.