A photoactivatable nano-liposome containing tripartite therapeutics for photothermal-triggered chemotherapy

Abstract

Chemotherapy represents a conventional method for cancer treatment, but it inevitably has the issues of low clinical efficacy, therapy resistance and severe side effects. In view of the unique characteristics of nanosystems that can deliver drugs in an effective and safe manner, we report photoactivatable nano-liposomes containing a hypoxia-responsive prodrug tirapazamine (TPZ), glucose oxidase (GOx) and indocyanine green (ICG) for photothermal-triggered chemotherapy of subcutaneous metastatic breast cancer. The nano-liposomes (termed IGT@NPs) are fabricated using a thermo-responsive liposome component to enable photoactivatable drug delivery via the photothermal effect. IGT@NPs mediate the local temperature increase under near-infrared (NIR) laser irradiation, not only allowing for photothermal therapy (PTT), but also achieving on-demand TPZ and GOx release. In the tumor microenvironment, GOx catalyzes the consumption of glucose and oxygen, resulting in aggravated hypoxia levels. As a consequence, TPZ is activated through the aggravated hypoxic microenvironment to trigger the chemotherapeutic action. Therefore, photothermal-triggered chemotherapy is achieved by IGT@NPs, which leads to the effective inhibition of primary tumor growth and metastatic tumor occurrence in subcutaneous 4T1 tumors. This current study thus provides a photoactivatable nanosystem containing tripartite therapeutics for cancer treatment with controllable and combined functions.