Light-Directed Microalgae Micromotor with Supramolecular Backpacks for Photodynamic Therapy

Abstract

In recent years, the development of micromotors for biomedical applications has surged. However, challenges such as immunogenicity and the difficulty in controlling motion direction have hindered their clinical translation. In this study, Chlamydomonas reinhardtii, a natural unicellular green microalgae known for its biocompatibility and phototaxis properties in hydrogen peroxide environments is applied, as a micromotor for efficient drug delivery and photodynamic therapy. 5-Aminolevulinic acid-loaded liposomes are anchored onto the surface of algae through host–guest complexation between β-cyclodextrin-modified algae and adamantane-modified liposomes. This created a micromotor capable of carrying a drug-loaded backpack for light-driven tumor targeting and drug delivery. Additionally, light irradiation activates the photosynthesis of chloroplasts in microalgae leading to oxygen production and alleviation of the tumor's hypoxic microenvironment. In tumor-bearing mice, light irradiation on tumor tissue directs the micromotor to accumulate in the tumor region, significantly increasing the local drug concentration from 0.007 to 0.069 mg mL⁻¹ compared to free liposomes. Furthermore, oxygen generated from photosynthesis enhances the efficacy of photodynamic therapy, resulting in complete tumor regression in Balb/c mice after 14 days. This system achieves a three-in-one effect, combining targeted drug delivery, oxygen generation, and photodynamic treatment. These findings hold promise for the advancement of micromotor-based biomedical applications.