Abstract
Biohybrid microswimmers exploit the swimming and navigation of a motile microorganism to target and deliver cargo molecules in a wide range of biomedical applications. Medical biohybrid microswimmers suffer from low manufacturing yields, which would significantly limit their potential applications. In the present study, a biohybrid design strategy is reported, where a thin and soft uniform coating layer is noncovalently assembled around a motile microorganism. Chlamydomonas reinhardtii (a single‐cell green alga) is used in the design as a biological model microorganism along with polymer–nanoparticle matrix as the synthetic component, reaching a manufacturing efficiency of ≈90%. Natural biopolymer chitosan is used as a binder to efficiently coat the cell wall of the microalgae with nanoparticles. The soft surface coating does not impair the viability and phototactic ability of the microalgae, and allows further engineering to accommodate biomedical cargo molecules. Furthermore, by conjugating the nanoparticles embedded in the thin coating with chemotherapeutic doxorubicin by a photocleavable linker, on‐demand delivery of drugs to tumor cells is reported as a proof‐of‐concept biomedical demonstration. The high‐throughput strategy can pave the way for the next‐generation generation microrobotic swarms for future medical active cargo delivery tasks.
Highlights
Over the past decade, biohybrid microrobots, in which living mobile microorganmicroorganism to target and deliver cargo molecules in a wide range of isms are physically integrated with untethbiomedical applications
We have recently explored C. reinhardtii as the live component of biohybrid microrobots for the active delivery of therapeutics.[7]
The nonliving component consists of a conformal layer around C. reinhardtii using a natural biopolymer chitosan through electrostatic interactions, where positively charged chitosan polymer attaches to the negatively charged C. reinhardtii cell wall
Summary
Biohybrid microrobots, in which living mobile microorganmicroorganism to target and deliver cargo molecules in a wide range of isms are physically integrated with untethbiomedical applications. When microalgae were incubated within the mixture of CSIONPs dispersed in chitosan solution, coating was dramatically enhanced as illustrated in Figure 1C (third row), in which the population of red fluorescent algal cells is significantly elevated. Fluorescence imaging of a single bare and biohybrid microalgae demonstrates the chitosan coating (indicated by green fluorescent) and CSIONPs (indicated by red fluorescence) on algal cell wall (Figure 2A). Drug loaded nanoparticles (CSIONPs-L-DOX) were attached on the surface of algal cell wall through electrostatic interactions as presented in Figure 1A previously. As a proof-of-concept cargo delivery demonstration, we modified the coating with a model drug DOX through a photocleavable linker, and showed uptake of DOX molecules by the cancer cells upon a light-stimuli. The high-throughput strategy presented in this study can be applied to a broad range of microorganisms, and advance the performance of the biohybrid microrobots for different applications
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