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Cancer metastasis, especially to the lungs, presents a formidable challenge in medicine. Lung metastases often evade effective treatment due to targeting difficulties and low drug accumulation in the lung tissue. Consequently, researchers have been diligently searching for new methods to treat lung metastases more effectively.

An innovative approach is detailed in a recent article published in Science Advances titled "Biohybrid microrobots locally and actively deliver drug-loaded nanoparticles to inhibit the progression of lung metastasis." The research, conducted by a team from the University of California, San Diego, highlights a novel solution. The team identified that the main reason chemotherapy drugs are ineffective against lung metastases is the inadequate drug delivery method, which fails to transport sufficient drug quantities to the deep lung tissues, resulting in drug concentrations too low to kill tumor cells. Therefore, the team focused on finding a new delivery method as the key to treating lung metastases.

In recent years, microrobots have garnered significant attention from researchers worldwide. Initially, microrobots were typically made of rigid metals or polymers. However, with advances in biotechnology, a new class of biohybrid microrobots has emerged. Biohybrid microrobots are functionalized single-celled microorganisms, such as algae, bacteria, or even sperm, using synthetic components. These microrobots harness the motility of living microorganisms to provide propulsion and transport synthetic payloads to perform various tasks. Among these microorganisms, algae have shown great promise as mobile bio-motors for various biomedical and environmental applications. Because these robots are essentially microorganisms, they are more easily degraded in the body or excreted through cellular metabolism, ensuring higher safety in treatments compared to traditional microrobots.

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Preparation and characterization of algae-NP(DOX)-robot.

  1. Schematic depicting the use of algae-NP(DOX)-robot for the treatment of melanoma lung metastasis. (B) Transmission electron microscopy image of RBC membrane–coated DOX-loaded nanoparticles [denoted NP(DOX)]. Scale bar, 100 nm. (C and D) Size (C) and surface zeta potential (D) of NP(DOX) and bare DOX-loaded polymeric nanoparticles [denoted PLGA(DOX)] (n = 3; mean + SD). (E and F) Drug loading yield (E) and encapsulation efficiency (F) of NP(DOX) and PLGA(DOX) (n = 3; mean + SD). (G) Schematic illustration of algae-NP(DOX)-robot, in which NP(DOX) is covalently conjugated onto algae via click chemistry. (H) Representative bright-field (BF) and fluorescent images of an algae-NP(DOX)-robot. Autofluorescence of algae chloroplast in the Cy5 channel; NP(DOX) in the RFP channel. Scale bar, 10 μm. (I) Pseudo-colored SEM image of an algae-NP(DOX)-robot. Algae in green; NP(DOX) in orange. Scale bar, 2 μm. (J) Optical absorption spectrum of algae-NP(DOX)-robot compared with bare algae and NP(DOX). a.u., arbitrary units. (K) Quantification of DOX loading on 1 × 106 algae at various initial drug inputs (n = 3; mean ± SD). (L) Representative flow cytometry histograms of algae before (gray) and after (red) functionalization with NP(DOX) at a 25-μg drug input. DOX is measured on the phycoerythrin (PE) channel.

Credit:DOI: 10.1126/sciadv.adn6157

Inspired by biohybrid microrobots and the unique characteristics of the lungs, the research team developed an algae-based microrobot as a new method for delivering drugs to lung metastases. The team designed a microrobot platform called "Algae-NP (DOX)-Robot," composed of natural green algae functionalized with polymeric nanoparticles loaded with doxorubicin (DOX) and coated with red blood cell membranes. The cell membranes enhance the biocompatibility of the algae microrobots, preventing immune system attacks during transport. In animal trials, researchers found that once the microrobots entered the lungs, they could swim and distribute the drug within lung tissues. Additionally, the microrobots offered significant advantages over conventional chemotherapy, such as avoiding the destruction of lung immune cells. The trials showed that the microrobots released higher drug concentrations and remained in the lungs longer. The median survival time of mice treated with algae microrobots increased from 27 days to 37 days. As previously mentioned, algae microrobots can be broken down into non-toxic components by immune cells and eventually cleared from the body.

Although this research has shown promising results in animal trials, further improvements are needed for the delivery method using algae's unique motility to transport chemotherapy drugs. The research team is also exploring techniques like magnetic guidance and ultrasonic capture to enhance drug concentration at specific targets within the body, allowing for more precise and rapid effects on tumors rather than normal cells.

Reference:

Zhang F, Guo Z, Li Z, Luan H, Yu Y, Zhu AT, Ding S, Gao W, Fang RH, Zhang L, Wang J. Biohybrid microrobots locally and actively deliver drug-loaded nanoparticles to inhibit the progression of lung metastasis. Sci Adv. 2024 Jun 14;10(24):eadn6157. doi: 10.1126/sciadv.adn6157. Epub 2024 Jun 12. PMID: 38865468; PMCID: PMC11168470.