Helicobacter pylori (H. pylori) is globally recognized as a high-priority pathogen associated with various gastric diseases, including peptic ulcers, chronic gastritis [1,2], gastric mucosa-associated tissue lymphomas [3], and gastric adenocarcinomas [[4], [5], [6]]. Moreover, H. pylori is estimated to infect more than half of the population worldwide [[7], [8], [9], [10], [11]]. Nowadays, H. pylori infection is eradicated with triple therapy using proton pump inhibitors (PPI) and two or three antibiotics (triple/quadruple therapy), either bismuth-based or bismuth-free (sequential and concomitant) [12]. Unfortunately, antibiotic resistance limits the effectiveness of these therapies [[13], [14], [15]], which also leads to the undesirable removal of intestinal symbiotic bacteria that are closely related to metabolic processes [[16], [17], [18]]. Therefore, there is a growing need to develop alternative approaches to eradicate H. pylori without causing antibiotic resistance or side effects.

Antimicrobial photodynamic therapy (aPDT) has attracted considerable attention as a new antibacterial therapy in recent years. PDT involves the use of harmless visible light in combination with a photosensitizer (PS) and oxygen present in and around cells. Visible light of an appropriate wavelength excites the non-toxic PS, which then reacts with oxygen to form singlet oxygen or other cytotoxic reactive oxygen species (ROS), which triggers a series of reactions in the biological system, leading to cell death and possibly bacterial resistance. However, aPDT with an exogenous photosensitizer (ex-PS) is a relatively complex clinical procedure that requires the administration of ex-PS and the avoidance of prolonged light exposure to prevent photosensitization. H. pylori produces and accumulates endogenous photosensitizers, a mixture of protoporphyrin IX (PpIX) and coproporphyrin (CP), which can sensitize and kill the bacterium upon illumination by visible light, particularly blue light [19,20], suggesting that aPDT without ex-PS is a promising novel approach to eliminating H. pylori infection in the human stomach.

The above porphyrins mainly absorb light at approximately 415 nm and, interestingly, at the longer wavelength of 630 nm [21]. The main limitation of PDT is the poor penetration of light through tissues: violet-blue light, which is commonly used to sensitize porphyrins, is absorbed by tissues and blood vessels. Within the visible light spectral range, red light seems to be a promising alternative because it is less attenuated by blood [22]. Considerable reduction of the bacterial load in patients by PDT has been repeatedly demonstrated using endoscopic light sources [[23], [24], [25]]. Nevertheless, this treatment cannot provide complete eradication, and it is invasive and associated with poor patient compliance.

Fortunately, approved photosensitizers can be initiated with relatively low-cost light-emitting diodes (LEDs), which have been proven to be as effective as traditional medical lasers [[26], [27], [28]]. Moreover, alternative endoscopic light sources in the form of endoscopic therapeutic capsules have been developed [29,30]. In particular, an innovative medical device was prepared into a swallowable capsule equipped with an LED unit [[31], [32], [33]] to perform PDT in the stomach in a minimally invasive way. Tortora et al. [31] first presented two ingestible capsules integrated with 8 LEDs (emitting at 405 or 625 nm) on an electronic board with a magnetic switch and battery. Both types of capsules, emitting red light (625 nm, 30 min, 16 J/cm2) or blue light (405 nm, 30 min, 9 J/cm2), acted on H. pylori with an antibacterial rate of approximately 96 %. Orsini et al. [34] further measured the functional temperature of the above capsules and verified their chemical resistance under conditions mimicking gastric and gut environments. Moreover, safety tests of the capsules under illumination and in transit through the gastrointestinal tract of a healthy minipig model verified the integrity of the capsules and the absence of side effects. However, developing LED capsules as a new technology for PDT of H. pylori infection faces many challenges, mainly associated with the trade-off between power supply and light power density.

Currently, LED devices are miniaturized by adopting two power modes: battery-based power supply or wireless charging [26]. The battery-powered mode suffers from limited battery capacity, with the voltage decreasing as the battery depletes, resulting in a short duration of the effective optical power. In contrast, wirelessly charged devices are constrained by the coil size, making it difficult to achieve light power that reaches the therapeutic threshold. Moreover, the power may destabilize as the distance between the wireless power supply and receiver varies. Therefore, current research is focused on exploring feasible and appropriate LED parameters on the basis of existing power supplies to achieve efficacious phototherapy of H. pylori infection.

In this study, we first investigated the dose–effect relationship of LED-mediated aPDT (LED-aPDT) with and without ex-PS against H. pylori at the bacterial suspension and biofilm levels. Then, we observed inflammation, immune infiltration, and intestinal flora before and after aPDT against H. pylori in SD rats.

This project focused on technical issues in the treatment of H. pylori infection using LED-based capsules. We first explored the dose–effect relationship of LED-aPDT with ex-PS and LED-aPDT without ex-PS in the treatment of H. pylori infection at the suspension and biofilm levels. Then, we observed inflammation, immune infiltration, and intestinal flora before and after aPDT of SD rats with H. pylori infection, demonstrating that aPDT(with ex-PS and without ex-PS) at 630 nm effectively killed H. pylori in vivo. Subsequently, an ingestible magnetically controlled LED capsule was designed on the basis of the above parameters, and its performance was characterized to provide reference for future development of LED capsule robots, thereby advancing the clinical application of PDT in the treatment of gastrointestinal H. pylori infection.