(23) However, considering the application of cancer treatment in the female reproductive tract, sperms are more suitable candidates to transport drugs than purely synthetic micromotors as they are naturally adapted to swim in such environment and possess practical advantages such as payload protection and reduced cytotoxicity thanks to their compact membrane. (22) Mg-based micromotors were also successfully used to deliver drugs in a mouse stomach to treat bacterial infections. For example, artificial flagellae have been reported for gene transfection of human embryonic kidney HEK 293 cells, through the transport of pDNA-loaded lipoplexes (21) and for the cargo-release of calcein-loaded liposomes to single mouse myoblasts in vitro. (20) To achieve targeted drug delivery, some fruitful attempts have also been shown by using synthetic micromotors. Sperms can also efficiently avoid dose dumping, which is regarded as a major issue of micelle carriers, thanks to their compact membrane system. (19) By doing so, the sperm membrane can protect drugs from body fluid dilution, immune reactions, and the degradation by enzymes. Sperm cells also have the extraordinary ability to encapsulate hydrophilic drugs, which have high DNA-binding affinity, (18) storing them in its crystalline nucleus.
(17)Ĭompared to other cellular drug carriers, sperms are naturally optimized to swim in the female reproductive system, which makes them promising candidates for the treatment of cervical cancer and other gynecologic diseases. (12) Nonetheless, it is noteworthy that rapid clearance or even autoimmune reactions might be caused by the immune response to certain bacteria. For example, magneto-aerotactic bacteria were reported to deliver drug-loaded liposomes to the hypoxic regions of tumor tissue in mice. (10, 11) Bacteria, with chemotactic properties (13) and/or with associated synthetic guidance components, (14-16) were shown to actively transport and deliver drugs into tumor tissue. Likewise, self-propelled cells, as a combination of cellular encapsulation and propulsion, have interested scientists all over the world due to their swimming performance in complex physiological microenvironments. (7)Macrophages and red blood cells with and without synthetic guidance or propulsion components have been reported as carriers for cancer therapy (8) and sustained drug release in blood, (9) respectively. (6) Stem cells, for example, have been used as a combinatorial drug delivery system toward regenerative therapy. (5) Among the most promising nano- and microcarrier approaches to overcome such hurdles are cellular drug delivery systems, where cells or microorganisms act as drug carriers, as they have advantages like membrane fluidity, ability to interact with other cells/tissue, long lifespan, and high biocompatibility. (1, 2) The current challenges include the unspecific uptake by other organs, (3) limited tissue penetration, (4) and the decrease of effective concentration due to the dilution in body fluids. The development of drug delivery systems that provide effective doses locally in a controlled way is one of the main goals in the worldwide fight against cancer.
This sperm-hybrid micromotor is a biocompatible platform with potential application in gynecological healthcare, treating or detecting cancer or other diseases in the female reproductive system. Overall, sperm cells are excellent candidates to operate in physiological environments, as they neither express pathogenic proteins nor proliferate to form undesirable colonies, unlike other cells or microorganisms. In our experiments, the sperm cells exhibited a high drug encapsulation capability and drug carrying stability, conveniently minimizing toxic side effects and unwanted drug accumulation in healthy tissues. The sperm release mechanism is designed to liberate the sperm when the biohybrid micromotor hits the tumor walls, allowing it to swim into the tumor and deliver the drug through the sperm–cancer cell membrane fusion. This system is demonstrated to be an efficient drug delivery vehicle by first loading a motile sperm cell with an anticancer drug (doxorubicin hydrochloride), guiding it magnetically, to an in vitro cultured tumor spheroid, and finally freeing the sperm cell to deliver the drug locally. A sperm-driven micromotor is presented as a targeted drug delivery system, which is appealing to potentially treat diseases in the female reproductive tract.
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