Microalgae oral drug carriers for gut microbiota homeostasis and intestinal disease/cancer treatment

We use microalga Spirulina platensis to construct an innovative oral delivery system for radioprotector Amifostine, showing comprehensive drug accumulation, effective radioprotection in the whole small intestine, beneficial gut microbiota homeostasis, and efficient disease treatment.
Microalgae oral drug carriers for gut microbiota homeostasis and intestinal disease/cancer treatment
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Protecting the whole small intestine from radiation-induced intestinal injury during the radiotherapy of abdominal or pelvic solid tumors remains an unmet clinical need. Amifostine is a promising selective radioprotector for normal tissues. However, its oral application in intestinal radioprotection remains challenging. Herein, we use microalga Spirulina platensis as a microcarrier of Amifostine to construct an oral delivery system. The system shows comprehensive drug accumulation and effective radioprotection in the whole small intestine that is significantly superior to free drug and its enteric capsule, preventing the radiation-induced intestine injury and prolonging the survival without influencing the tumor regression. It also shows benefits on the gut microbiota homeostasis and long-term safety. Based on a readily available natural microcarrier, this work presents a convenient oral delivery system to achieve effective radioprotection for the whole small intestine, providing a competitive strategy with great clinical translation potential.

figure 1

Fig. 1: Synthesis and characterization of SP@AMFa Schematic illustration of synthetic protocols and radioprotective mechanisms of SP@AMF. I. SP protects AMF from gastric destruction. II-IV. SP@AMF gradually degrades and slowly releases AMF through the whole small intestine (duodenum, jejunum and ileum). V. SP@AMF protects intestinal tissue from radiation-induced epithelial injury, inflammation, and fibrosis. VI. SP@AMF maintains the health of gut microbiota. b SP cultivated in medium and its lyophilized powder. c PBS suspension of the prepared SP@AMF and its bright-field microscope and SEM images. Scale bar = 20 µm. d Lyophilized powder of the mass prepared SP@AMF. The net weight of SP@AMF in the bottle is 7.331 grams. e Fourier transform infrared (FTIR) spectra of SP, AMF, and SP@AMF. f Drug loading efficiency (DLE) under various concentrations of AMF loading solution (n = 3 independent experiments). The data show means + SD. g Release profiles of AMF from SP@AMF in simulated intestinal fluid (SIF) after being treated by simulated gastric fluid (SGF) for 1 and 2 h. Untreated SP@AMF was used as control (n = 3 independent experiments). The data show means + SD. h pH values of the SGF supernatant containing different concentrations of SP@AMF (n = 3 independent experiments). The data show means + SD. P was calculated using two-tailed t-test.

Fig. 2

Fig. 2: In vitro, SP@AMF shows lower toxicity and more effective protection on normal cells than free AMF. a Viabilities of the IEC-6 cells (small intestinal epithelium cells) after incubating with various concentrations of SP, AMF, and SP@AMF for 24 h. The viabilities were determined by an MTT assay kit (n = 6 biologically independent cells). The data show means + SD. P was calculated using two-tailed t-test. b Calcein-AM/PI fluorescence images (green, living cell; red, dead cell) of the IEC-6 cells irradiated by 6 Gy X-ray (IR) (except for PBS group) after 1, 2, 3, or 4 h of incubation with the renewed medium in different groups. Scale bar = 100 µm. Experiment was repeated three times independently with similar results. cf Crystal violet staining (c, d) and quantification (e, f) of the surviving colonies of IEC-6 cells and CT26 cells (colorectal cancer cells) irradiated by 0, 2, 4, and 6 Gy X-ray in different treatment groups (PBS, SP, AMF, and SP@AMF) (n = 3 biologically independent cells). The data show means + SD. P was calculated using two-tailed t-test. n.s. no significance (P > 0.05).

figure 3

Fig. 3: Compared with free drug, SP-based system shows retention among villi, progressive degradation, and extensive drug distribution throughout the small intestine.

 In summary, we successfully constructed SP@AMF, a natural microcarrier-based orally delivered system, to effectively prevent the healthy intestine from radiation-induced damage in radiotherapy. Benefiting from the comprehensive intestinal biodistribution, the natural microcarrier, SP, significantly improved the radioprotection of AMF on the whole intestine. Possessing significant superiority to a commercial capsulation, the benefits on flora balance, as well as the high safety for long-term use, SP@AMF shows great potential to be applied in clinical radiotherapy of abdominal/pelvic tumors. Our study used readily available natural material to facilely construct a competitive radioprotective strategy with high translational potential in cancer radiotherapy.

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Dr. Xingcai Zhang, Harvard/MIT Research Fellow; Science Writer/Editorial (Advisory) Board Member for Springer Nature, Materials Today, Royal Society of Chemistry, Wiley; with 5 STEM degrees/strong background in sustainable Nature-derived/inspired/mimetic materials for biomed/sensing/catalysis/energy/environment applications, with more than 100 high-impact journal publications in Nature Reviews Materials, Nature Nanotechnology, Nature Medicine, etc. https://scholar.google.com/citations?hl=en&user=2vDraMoAAAAJ&view_op=list_works&sortby=pubdate

https://scholar.harvard.edu/xingcaizhang 

https://orcid.org/0000-0001-7114-1095

Contact: Dr. Xingcai Zhang xingcai@mit.edu  chemmike1984@gmail.com +1-2253041387 wechat:drtea1

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