Living Microalgae-Based Magnetic Microrobots for Calcium Overload and Photodynamic Synergetic Cancer Therapy

Abstract

The combination of Ca2+ overload and reactive oxygen species (ROS) production for cancer therapy offers a superior solution to the lack of specificity in traditional antitumor strategies. However, current therapeutic platforms for this strategy are primarily based on non-targeting nanomaterials, leading to undesirable off-target side effects. Additionally, resistance to ROS and apoptosis induced by the hypoxic tumor microenvironment (TME) further limits therapeutic efficiency. Herein, a magnetic microrobot based on living Spirulina Platensis (SP), which is coated with a double layer of Fe3O4 nanoparticles (NPs) and CaCO3 NPs. The microrobots can accumulate in tumor regions under magnetic attraction, which produces a high-Ca2+ environment under the acidic TME and facilitates Ca2+ overload under ultrasound (US) stimulation. Meanwhile, sufficient oxygen (O2) production by photosynthesis helps alleviate hypoxia and promotes in situ ROS production by chlorophyll-mediated photodynamic therapy (PDT), which can coordinate with Ca2+ overload to induce cell apoptosis. With these unique properties, the SP-based microrobots offer a promising microrobotics-based strategy for in situ Ca2+ accumulation and ROS production, contributing to a precise and effective way for cancer treatment.