Microscopy Meets Medicine: Spirulina-Derived Nanoparticles Take Aim at Cancer

This article from the International Journal of Nanomedicine presents a promising new biomimetic strategy that makes use of natural resources as an alternative in cancer therapy. The Researchers have created Spirulina-derived Nanoparticles (sNPs) using a solvent-free process and with the aid of centrifugation and sonication technique. The lysosomes sus-pended averaged an approximate size of 126nm, a polydispersity index of 0.14 and a zeta potential of -38mV. This study stands out as one of the most innovative due to the use of microscopy which acts as a visual aid as well as a basic component for experimental validation. Researchers are really pushing for new ways to treat changes in the cancer therapy field as it keeps getting modified. Chemotherapy, radiation, etc., are standard and still effective in curing cancers but have terrible side effects, and hence are not selective.
These nanoparticles are from Spirulina platensis, a blue-green microalga renowned for having therapeutic and nutritional properties. This nanomaterial was promising for an environment-friendly green approach because it is prepared through a solvent-free process entailing centrifugation and sonication to obtain Spirulina-derived Nanoparticles (sNPs), which yield liposome-like particles measuring about 126 nm in diameter, with a polydispersity index of 0.14 and a zeta potential of -38 mV. This study is indeed among the most innovative as it utilizes microscopy as a visual complement as well as assay methodology for experimental validation.
In sophisticated microscopy methods, particularly fluorescence microscopy and flow cytometry (FACS), the researchers were able to verify the selective internalization of these sNPs into cancer cells, thus providing a compelling basis for a notion of their specific lethal effects. The cytotoxicity of sNPs was tested against various cancer cell lines such as MCF-7 (breast), Caco-2 and HT-29 (colorectal), and TR-146 (buccal) and compared with the results from the normal breast epithelial cell line MCF-10A. The results were shocking: healthy MCF-10A cells showed less than 5% death in all cases while the malignant cells exhibited significant death rates ranging from 30% to 80% depending on the dose and duration of exposure.
These deductions were confirmed by data obtained by the XTT which employs a colorimetric technique to assay cellular viability. However, microscopy unraveled the true story. To identify the sNPs and monitor their uptake, the researchers employed DiI, a red fluorescent lipophilic dye. The DAPI-stained nuclei glowed blue and the DiI-labeled sNPs looked red in TR-146 cells in combination with a fluorescence microscope. Instead of just sticking to the cancer cells’ surfaces, the overlay of these signals demonstrated that the nanoparticles had been internalised into the cells. Additionally, quantitative data from flow cytometry revealed that all malignant lines had 100% cellular uptake, while MCF-10A cells that were not cancerous only displayed 60% uptake.
Strikingly enough, the cytotoxicity levels reported were highly correlated to MFI, or Mean Fluorescence Intensity, which measures the amount of fluorescence detected per cell. Highest MFI was seen in the TR-146 cell line (12,222) and moderately in the MCF-7 cell line (7,509), but less in the HT-29 and Caco-2 cell lines (around 2,800). These results suggest that the efficacy of sNPs in cancer is strongly influenced by these cells’ suitable internalization efficiency. The researchers then used endocytic inhibitors MβCD, which inhibits caveolae-mediated endocytosis, and EIPA, which inhibits macropinocytosis, to investigate the uptake mechanism. Their application demonstrated that caveolae-mediated endocytosis predominantly operated in sNPs’ internalization in cancer cells, particularly in TR-146 and Caco-2 cells, whereby blocking this pathway lowered mortality significantly.
Yet, macropinocytosis was non-essential for MCF-7 and MCF-10A cells but was relevant in HT-29 cells. This extensive knowledge of cellular entrance stemmed from the combined application of cell biology and imaging techniques. Higher fluidity and metabolic activity of cancer cells further rationalize selectivity of sNPs, owing to differential endocytic traffic between cancer and normal cells. This is a well-reported phenomenon in nanoparticle literature. Lack of delayed cytotoxicity in MCF-10A cells up to a week after recovery further reaffirmed low off-target effects of sNPs, thereby corroborating this particular action. Male-derived Caco-2 cells were evidently more sensitive to sNP-induced death compared to female-derived HT-29 cells, actuation disparities due to sex.
These results raise the possibility of personalised nanomedicine by pointing to the intricate interactions among cell biology, nanoparticle interaction, and patient-specific variables including sex. The incorporation of microscopy was crucial to the study’s success since it allowed for the visualisation, validation, and quantification of nanoparticle behaviour at the cellular level. High-resolution spatial and statistical confirmation of sNP uptake was made possible by the DiI and DAPI dual-staining method in conjunction with flow cytometry and image analysis utilising programs like ImageJ. Essentially, microscopy served as a map and a microscope, assisting researchers in navigating the nanoscale terrain of cytotoxicity and drug delivery. By using only natural, edible materials instead of potentially harmful synthetic agents, this study separated out from the many others that rely on metallic or chemically functionalized nanoparticles.Yet, macropinocytosis was non-essential for MCF-7 and MCF-10A cells but was relevant in HT-29 cells. This extensive knowledge of cellular entrance stemmed from the combined application of cell biology and imaging techniques. Higher fluidity and metabolic activity of cancer cells further rationalize selectivity of sNPs, owing to differential endocytic traffic between cancer and normal cells. This is a well-reported phenomenon in nanoparticle literature. Lack of delayed cytotoxicity in MCF-10A cells up to a week after recovery further reaffirmed low off-target effects of sNPs, thereby corroborating this particular action. Male-derived Caco-2 cells were evidently more sensitive to sNP-induced death compared to female-derived HT-29 cells, actuation disparities due to sex. Spirulina-derived nanoparticles are definitely good candidates for efficacious and biocompatible potentially therapeutic development in the future. Furthermore, they could be potential candidates for oral or mucosal delivery systems because of their supposed mucoadhesive properties, characteristically demonstrated in previous studies by the same group. The conclusion of the study says that sNPs have a good promise of being a safe and selective therapeutic agent against various malignancies. It recommends further research on their molecular mechanisms, effectiveness in vivo, and possible clinical applications. It represents a significant stride toward personalised, biocompatible, and less invasive cancer treatment. More than just pictures, microscopy reveals mechanisms, affirms theories, and realizes the reality of precision medicine–nature shaped, science-improved–closer.

Fluorescence microscopy images showing the uptake of sNPs labeled with DiI (red) by TR-146 buccal cancer cells. The top left image shows the DiI-labeled sNPs
(red), the top right image displays the DAPI-stained nuclei of TR-146 cells (blue), and the bottom image is a merged overlay showing the internalization of sNPs within the
cells, as evidenced by the overlap of red and blue signals. Scale bars represent 100 μm.

Reference- Drori E, Rahamim V, Patel D, Anker Y, Meir S, Uzan G, Drori C, Anker Y, Azagury A. The Selective in vitro Cytotoxicity of Spirulina-Derived Nanoparticles: A Novel Biomimetic Approach to Cancer Therapy. Int J Nanomedicine. 2025;20:4285-4298
https://doi.org/10.2147/IJN.S498865

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