(Nanowerk Spotlight) The precise delivery of cancer drugs to tumors has remained one of medicine’s most difficult challenges. Traditional chemotherapy affects the entire body indiscriminately, while newer targeted therapies often fail to penetrate deep into tumor tissue. Scientists exploring microscopic robots as a solution have faced persistent obstacles: synthetic materials trigger immune responses, chemical propulsion systems lack precise control, and complex electronics are difficult to miniaturize safely for use in the body.
Meanwhile, photodynamic therapy emerged as a promising treatment that uses light-activated drugs to destroy cancer cells. This approach offers precision, as drugs only become active when exposed to specific wavelengths of light. However, its effectiveness has been limited by poor drug delivery to tumors and the low-oxygen environment inside cancer tissue, which reduces the therapy’s potency.
The field of biohybrid robotics has offered potential solutions by combining living cells with synthetic materials. Bacteria and other microorganisms can swim naturally through body tissues, but controlling their movement has proved challenging. Some microorganisms respond to light, magnetic fields, or chemical gradients, but harnessing these responses for precise medical applications has remained elusive.
Recent advances in molecular engineering, particularly in modifying cell surfaces and creating specialized drug carriers, have opened new possibilities. These techniques allow researchers to attach therapeutic payloads to living cells while preserving their natural functions. Additionally, improved understanding of how single-celled organisms navigate and respond to environmental signals has suggested ways to guide them to specific locations in the body.
Building on these developments, researchers have now turned to an unlikely source for medical robotics: photosynthetic algae. These microscopic organisms offer several advantageous properties – they swim efficiently, respond to light, and naturally produce oxygen through photosynthesis.
Reporting in Advanced Functional Materials (“Light-Directed Microalgae Micromotor with Supramolecular Backpacks for Photodynamic Therapy”), researchers at the University of Macau have harnessed these unique properties of algae in a novel cancer treatment system. They chose Chlamydomonas reinhardtii, a single-celled green algae about 10 micrometers in diameter – roughly one-tenth the width of a human hair. These organisms navigate using two microscopic tails called flagella and possess a light-sensitive “eyespot” that allows them to respond to light direction.
The team transformed these algae into drug carriers through a precise molecular modification process. They coated the algae’s surface with ring-shaped molecules called cyclodextrins, which function like microscopic docking stations. These stations can securely grip specially prepared drug containers – tiny spheres of fat called liposomes – through a lock-and-key mechanism at the molecular level. The liposomes carry 5-aminolevulinic acid, a drug that generates cell-killing reactive oxygen when exposed to red light.
Scheme showing a bionic micromotor with backpacks (R-motor) developed by conjugating ADA-modified liposome (loaded with a photosensitizer) on the surface of CD-modified C. reinhardtii through host–guest interaction, which precisely targets and accumulates at the tumor site, producing oxygen while simultaneously enabling photodynamic therapy (PDT) for tumor treatment. (Image: Reprinted with permission by Wiley-VCH Verlag)
This system takes advantage of a unique feature of tumor biology: cancer tissues often contain elevated levels of hydrogen peroxide, which enhances the algae’s natural tendency to swim toward light. When injected into the bloodstream and guided by red light focused on the tumor, the algae actively swim against blood flow and accumulate at the cancer site. Their natural swimming ability allows them to penetrate deep into tumor tissue, reaching areas that passive drug carriers cannot access.
Laboratory tests revealed that these algae-based robots maintain their ability to photosynthesize after modification, producing oxygen that helps counter the low-oxygen environment typical of tumor tissue. This oxygen production serves two crucial functions: it helps maintain the algae’s swimming ability and improves the effectiveness of the light-activated cancer drug.
In trials with mice bearing breast tumors, the researchers demonstrated the system’s precision and effectiveness. When they shined red light on tumor sites, the drug concentration in the illuminated areas increased tenfold compared to treatments using drug-containing liposomes alone. The algae’s oxygen production created better conditions for the light-activated drug to work, leading to complete tumor regression after two weeks of treatment.
Importantly, the treatment showed minimal effects on healthy tissue. The light-activated drug only becomes toxic when exposed to specific wavelengths of red light, which the researchers focused solely on tumor areas. Blood tests and organ examinations revealed no significant side effects, suggesting the algae robots are well-tolerated by the body. In some cases, the treatment appeared to help normalize blood chemistry that had been disrupted by cancer.
The system’s effectiveness stems from its three synchronized mechanisms: precise guidance to tumors using light, enhanced oxygen levels through photosynthesis, and targeted drug activation. This combination addresses multiple barriers that have limited previous cancer treatments.
Several technical challenges must be addressed before this technology could enter clinical trials. The body eventually clears the algae through immune responses, typically within 48-72 hours of injection. Current light-guidance techniques limit treatment to tumors that can be reached by red light, which penetrates only about one centimeter into tissue. The researchers suggest future work should focus on extending the algae’s survival time in the body and developing methods to reach deeper tumors, possibly using implanted light sources or bioluminescent markers.
Despite these limitations, this work demonstrates how combining living organisms with synthetic drug delivery systems can create sophisticated medical robots. The approach offers new possibilities for precise, effective cancer treatment while minimizing side effects, potentially opening avenues for treating other diseases that require targeted drug delivery.
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