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

A magnetic microrobot fabricated by Spirulina platensis is proposed to accumulate in tumor regions and generate in situ high calcium concentration and sufficient oxygen. These characteristics of the microrobot present a strategy for triggering calcium overload therapy and chlorophyll-mediated photodynamic therapy, and such combination resulted in a synergetic antitumor effect via mitochondrial-mediated pathways.

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.