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. 2025 Sep 15;15(10):347. doi: 10.1007/s13205-025-04519-8

Composites based on bismuth nanoparticles: antimicrobial and anticancer properties

R O Shaikenov 1,✉, I S Garkushina 2
PMCID: PMC12436264  PMID: 40964656

Abstract

Every year millions of people die from bacterial infections and cancer, which is a serious global health problem. The rapid spread of antibiotic resistance among pathogenic strains of bacteria is a particular cause for concern. Bismuth nanoparticles, especially quantum dots, demonstrate high potential in the diagnosis and treatment of diseases due to their unique properties. They have antimicrobial activity both in combination with irradiation and on their own, making them a promising alternative to traditional antibiotics. In addition, bismuth nanoparticles exhibit cytotoxicity toward cancer cells, especially when exposed to infrared or X-ray radiation, making them perspective agents for cancer therapy. This review discusses various types of bismuth-containing nanoparticles, their antimicrobial and anti-tumor properties, as well as the main mechanisms of action associated with the generation of reactive oxygen species and the photo-thermal effect.

Keywords: Bismuth, Quantum dots, Nanoparticles, Antimicrobial, Anticancer, Mechanism of action

Introduction

Bacterial infections are widespread diseases in the world. Before the COVID-19 pandemic, more than 70 million people died each year from various bacterial infections. The COVID-19 pandemic resulted in people who contracted the virus having an increased risk of bacterial infection and an increased risk of re-infection (Piantoni et al. 2023). In addition, bacterial infections weaken the body and can lead to death from secondary causes (Ikuta et al. 2022). Other dangerous diseases are oncological illnesses. There are nearly 20 million cases of cancer and 10 million deaths because of cancer each year (Ferlay et al. 2021). Therefore, the development of treatment against these diseases is an important task of modern medicine.

Composites with quantum dots could potentially be used as drugs as well as diagnostic tools. Quantum dots are nanoparticles that exhibit optical and electronic properties which depend on their size and composition. Quantum dots have small sizes: from 1.5 to 10.0 nm. Recently, technologies using quantum dots have been applied in industry as well as in the diagnosis and therapy of diseases (Bailey et al. 2004). Moreover, it has been discovered that quantum dots have antimicrobial and anti-cancer properties (Bailey et al. 2004; Rajendiran et al. 2019; Shahbazi-Gahrouei et al. 2023). Bismuth-based quantum dots are particularly interesting in this field as this metal is practically non-toxic to humans, unlike other heavy metals (Shahbazi-Gahrouei et al. 2023; Rosário et al. 2023).

The value and contribution of this review lies in the analysis of bismuth quantum dots, which are used to treat both bacterial infections and cancer, taking into account the presence or absence of radiation. The aim of this review is to consider bismuth quantum dots and composites based on them as a promising drug against bacterial and oncological diseases. In this paper, we use the terms ‘quantum dots’ and ‘nanoparticles’ interchangeably, since quantum dots are a subset of nanoparticles.

Basic information about bismuth

Bismuth is a chemical element with an atomic number 83. It is located in group 15 of the Periodic Table of Chemical Elements, in the 6th period of the table. Under normal conditions, it is a shiny silvery-white metal. Its atomic weight is 208.98 u. Bismuth compounds have been known to mankind since ancient times, but it was not until modern times that it was discovered that it is an element, i.e., a simple substance.

Bismuth is capable of oxidation degrees from 0 to + 5, but the main forms are represented as Bi (III) and Bi (V). Bi (III) forms complexes with sulfur and sulfur-containing molecules such as cysteine, and also has a high affinity for nitrogen and oxygen ligands (Sun Hongzhe et al. 1997).

Complexes with Bi (III) have a variety of structures Due to the 6s2 pair of electrons. With coordination numbers between 3 and 5, these can be trigonal pyramidal, trigonal bipyramidal and square (Yang and Sun 2007).

Use of bismuth nanoparticles in biology and medicine

Bismuth compounds have been used since ancient times for the treatment of illnesses, including bacterial infections. Nowadays, bismuth is used in composites and ligands, as well as combined with photodynamic and photometric therapy (Xu et al. 2016; Rosário et al. 2023).

Bismuth nanoparticles are also used in computed tomography to improve image quality (Rabin et al. 2006; Kinsella et al. 2011). In addition, it has been discovered that bismuth nanoparticles can be used for cancer theragnostics, i.e., the simultaneous diagnosis and treatment of the disease (Gomez et al. 2021; Ganapathy et al. 2022). In this review, we have focused specifically on the therapeutic effects of nanoparticles.

Bismuth nanoparticles preparation and characterization

To date, many methods for synthesis of bismuth nanoparticles have been developed. One popular group of methods is hydrothermal/solvothermal/ionothermal synthesis of BiNPs. These synthesis methods involve the crystallization of bismuth-based nanoparticles in Liquid solvents at high temperatures and pressures, usually using an autoclave. Hydrothermal methods use water as a solvent, while solvothermal methods use organic solvents and ionothermal methods use ionic Liquids. This group of methods allows for energy-efficient and cost-effective production, providing control over particle size, shape, and crystallization by regulating temperature, reaction time, and pH. These methods can produce particles in a wide range of sizes, from 10 to 300 nm (Shahbazi et al. 2020).

Another popular synthesis method is the sol–gel method. The sol–gel method provides high uniformity, morphology control, and lower processing temperatures when producing BiNPs. In this method, the reaction mixture includes two phases: a colloidal solution (sol) and a gelation phase that forms an interconnected network. The characteristics of the resulting particles can be controlled by changing the synthesis parameters: the nature of the solvent, pH, temperature, gelation time, and additives such as surfactants or catalysts. This method can be used to obtain particles ranging in size from 50 to 250 nm (Shahbazi et al. 2020).

In addition, green synthesis of nanoparticles has recently been gaining popularity. Green synthesis is an environmentally friendly and sustainable approach to the production of bismuth-based nanoparticles using biological resources, such as plant extracts, microorganisms, and biopolymers. This method has a number of advantages: no toxic by-products, reaction under environmental conditions. Synthesis using plants is the most common environmentally friendly method, in which phytochemicals (such as flavonoids, terpenoids, alkaloids) act as reducing agents and stabilizers. Microbial synthesis involves bacteria or fungi that produce enzymes that reduce bismuth salts to nanoparticles. Biopolymers and natural surfactants can help control particle size and morphology while increasing biocompatibility. This method can produce particles ranging in size from 10 to 70 nm (Dousari et al. 2024).

Zeta potential plays a key role in the stability of colloidal solutions of nanoparticles in water or biological media. Higher absolute values (typically above + 30 mV or below − 30 mV) suggest better colloidal stability, preventing aggregation, whereas values near 0 lead to instability and rapid aggregation or agglomeration. Polymers such as β-cyclodextrin or PEG are used to control the zeta potential. Also, as soon as nanoparticles enter biological fluids, proteins adsorb onto their surfaces, forming the so-called corona that can significantly alter the effective surface charge and zeta potential. However, the formation of the corona depends on the composition of the medium, the presence of metal ions and the pH. Controlling these factors and selecting the composition of the nanoparticles allows optimal conditions to be achieved in biological media (Bashiri et al. 2023; Alex and Mathew 2023).

Antimicrobial properties of bismuth nanoparticles

Effective treatment of bacterial infections is the backbone of modern healthcare. It enables the realization of complex medical technologies: transplantation and chemotherapy. However, the overuse of antibiotics inevitably leads to the development of resistance in bacteria and forces the development of new drugs. Therefore, drug-resistant bacterial infections pose a threat to public health. Antibiotic resistance genes are transferred between bacterial strains, leading to a rapid increase in multidrug-resistant bacteria (Larsson and Flach 2022; Urban-Chmiel et al. 2022).

The use of bismuth nanoparticle composites may provide a safe alternative in the fight against bacterial infections. The antibacterial effect of certain nanoparticles summarised in Tables 1 and 2. Also anticancer properties of nanoparticles, that can be beneficial in therapy, are presented in Table 3.

Table 1.

Bi-nanoparticles and efficiency of their antibacterial properties

Nanoparticles Bacteria strain % Of inhibition Concentration of nanoparticles References
With irradiation Without irradiation
Bi2S3 Escherichia coli 100 ≈ 0 0.4 mg/ml (Sun et al. 2019)
AgVO3/BiO2-X MRSA 100 0 50–500 μg/ml (Wang et al. 2021)
AgBiS2 Staphylococcus aureus 100 ≈ 40 6–60 μg/ml (Wen et al. 2021)
Escherichia coli 100 ≈ 40
Ag-Bi@SiO2 MRSA 100 ≈ 25 4–1024 μg/ml (Cao et al. 2020)
Bi2Se3 NPs/PEI Staphylococcus aureus 100 ≈ 0 10–80 ppm (Gorle et al. 2018)
Escherichia coli 100 ≈ 0
Bi2O3 Bacillus cereus – 93,8 0.5–15 mg/ml (Chinnappa Reddy et al. 2022)
Pseudomonas aeruginosa – 93,8
PVP-Bi Candida albicans – ≈ 83,5 0.5–256 μg/ml (Vazquez-Munoz et al. 2020)
Staphylococcus aureus – 100
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The maximum and minimum percentages of inhibition were taken in each paper

Table 2.

Bi-nanoparticles and efficiency of their antibacterial properties

Nanoparticles Bacteria strain Zone of inhibition, mm Concentration of nanoparticles References
Bi2S3 Staphylococcus aureus 15 50 µL/disk (Batool et al. 2021)
Escherichia coli 21
Bi2Se3/GO/PVA Escherichia coli 17 15 and 25 μg/ml (Imran et al. 2022)
Pseudomonas aeruginosa 18
CuxBi2-xSe3 Escherichia coli 14 20 mg/ml (Ahmad et al. 2022)
Pseudomonas aeruginosa 29
g-C3N4/CS-Bi2O3 Escherichia coli 2,85 10 and 20 mg/ml (Ikram et al. 2023)
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Disk-diffusion method

The maximum and minimum percentages of inhibition were taken in each paper

Table 3.

Bi-nanoparticles and efficiency of their anticancer properties

Nanoparticles Cell line % Of inhibition Concentration of nanoparticles References
With irradiation Without irradiation
AgBi2S NIH/3T3 60 – 6–120 μg/ml (Wen et al. 2021)
PVP-Bi U14 65 0 31–500 μg/ml (Lei et al. 2017)
Bi@GEL HepG-2 95 10 31–500 μg/ml (Liu et al. 2020)
HeLa 93 7
Bi2Se3@AIPH HepG-2 90 0 40 μg/ml (Li et al. 2019a)
Bi@CCM CT26 – 17 10–100 μg/ml (Ren et al. 2021)
F-RBC Bi 4T1 85 10 5–100 μg/ml (Deng et al. 2018)
Bi2O3 (90 nm) MCF-7 98 12 0.05 μM (Zulkifli et al. 2018)
Bi2O3 9L 93 – 50 μg/ml (Stewart et al. 2016)
BiO-Cis MCF-7 – 97 0.05–500 μM (Sisin et al. 2019)
MDA-MB-231 – 100
NIH/3T3 – 82
Bi2S3@BSA-MTX SW480 75 75 3.3–300 μg/ml (Faghfoori et al. 2020)
Bi2Se3@Sec BEL-7402 85 0 50 ppm (Du et al. 2017)
BisBAL HCT-116 – 80 0.125–100 μM (Cabral-Romero et al. 2020)
HeLa – 89
DU145 – 100
LL47 (MaDo) – 79
Bi2O3 (Thermo Fisher Life Technologies, USA) MCF-7 – 83 0.5–100 μg/ml (Alamer et al. 2020)
Bi2O3 (Sigma Aldrich, USA) MCF-7 – 66 1–300 μg/ml (Ahamed et al. 2019)
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The maximum and minimum percentages of inhibition were taken in each paper

Antimicrobial properties of bismuth nanoparticles under irradiation

In most of the research papers, nanoparticles are used in combination with some kind of irradiation: lamp or laser (Li et al. 2022a).

Sun, H et al. found that bismuth sulfide nanoparticles under IR irradiation effectively inhibit the growth of Escherichia coli in vitro (Sun et al. 2019). Similar results were obtained by Yuan Li et al. when studying bismuth sulfide in complex with acetylcholine and S-nitrosothiol. In research, the complex could effectively inhibit the growth of several bacterial strains in vitro and effectively control Staphylococcus aureus in vivo (Li et al. 2022b).

Also, silver and bismuth compounds are capable of exhibiting antibacterial activity. Changyu C et al. discovered that the combination of bismuth and silver particles in porous silicon, alongside IR laser irradiation, effectively inhibits the growth of Staphylococcus aureus in vitro and in vivo (Cao et al. 2020). Wen S et al. obtained similar outcomes in the research of AgBiS2 nanoparticles on Staphylococcus aureus and Escherichia coli in vitro. Moreover, IR laser reduced bacterial survival to almost 0% although particles without irradiation only reduced survival to 60% (Wen et al. 2021).

Bismuth and selenium compounds are also frequently used. For example, Gorle, G et al. created a composite of Bi2Se3 and polyethylenimine nanoparticles. The composite showed high antimicrobial properties against Escherichia coli and Staphylococcus aureus in vitro (Gorle et al. 2018).

However, in addition to IR radiation, xenon lamp light and even sunlight can also be used. Wang R et al. found that AgVO3/BiO2 nanoparticles can inhibit the growth of Staphylococcus aureus (MRSA) in vitro under xenon lamp irradiation and also inhibit the growth of the same bacterium in vivo under sunlight irradiation (Wang et al. 2021).

All researchers have identified two primary mechanisms of antibacterial activity: heat generation and formation of reactive oxygen species (ROS). These methods of combatting infection could serve as an alternative to antibiotics, as pathogenic bacterial growth is optimal between 35 and 37 ℃, while temperature of media with nanoparticle under IR laser can achieve up to 50–55 ℃ (Gorle et al. 2018; Li et al. 2022b). Although bacteria are able to defend themselves against the ROS through their own metabolic pathways (antioxidant defense include decarboxylation of pyruvate and α-ketoglutarate, the glyoxylate shunt and pentose phosphate pathway and other reactions) exposure to ROS is still an effective way of disinfection (Li et al. 2021a). Therefore, these mechanisms can be considered as effective ways of antibacterial therapy. Some examples of successful experiments against bacteria are presented in Fig. 1.

Fig. 1.

Fig. 1

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Antimicrobial properties of bismuth nanoparticles: a Bismuth and sulfur nanoparticles were used for photo-thermal therapy. The number of Escherichia coli bacteria decreased significantly after the application of nanoparticles and a laser (Sun et al. 2019).

Copyright 2018, Wiley–VCH. b Silver/bismuth nanoparticles in SiO2 spheres had a significant antibacterial effect against methicillin-resistant Staphylococcus aureus under the influence of a NIR laser. Reproduced with permission (Cao et al. 2020).Copyright 2020, Wiley–VCH. c Nanocomposites of Bi2Se3 and graphene oxide in the presence of poly(vinyl alcohol) had a significant antibacterial effect against Escherichia coli and Pseudomonas. Reproduced with permission (Imran et al. 2022). Copyright 2022, Elsevier. d Bi2O3 nanoparticles almost completely suppressed the growth of Bacillus cereus and Pseudomonas aeruginosa in an in vitro experiment. Reproduced with permission (Chinnappa Reddy et al. 2022). Copyright 2022, Elsevier

Antimicrobial properties of bismuth nanoparticles without irradiation

However, besides nanoparticles that exhibit antimicrobial properties under radiation, there are also nanoparticles that are toxic to bacteria by themselves, in the absence of additional conditions.

Zahida et al. found that Bi2Se3 nanoparticles effectively inhibited the growth of Staphylococcus aureus and Escherichia coli in vitro. Moreover, the toxicity of the particles was comparable to that of tigecycline and significantly superior to that of levofloxacin (Batool et al. 2021). Also, Ahmad D et al. investigated the antibacterial activity of Bi2Se3 and Bi2Se3 doped with copper. It was found that both types of nanoparticles have antimicrobial activity, and increasing the copper content increased the antimicrobial activity (Ahmad et al. 2022). Similar results were obtained by Imran et al., they investigated a composite based on Bi2Se3, graphene oxide and polyvinyl alcohol. The composite had antimicrobial properties against Pseudomonas aeruginosa and Escherichia coli in vitro (Imran et al. 2022).

Ikram M et al. investigated the antibacterial activity of bismuth nanoparticles with graphite carbon nitride and carbon spheres. The composite exhibited antibacterial properties, but compared to the positive control, ciprofloxacin, the efficacy of the composite was low (Ikram et al. 2023).

Chinnappa Reddy and et al. published the data that bismuth (III) oxide made by combustion method was able to inhibit the growth of Bacillus cereus and Pseudomonas aeruginosa by more than 90% at a concentration of 15 mg/ml (Chinnappa Reddy et al. 2022).

Also, bismuth nanoparticles in composite with poly(vinyl pyrrolidone) (PVP) was investigated by Vazquez-Munoz, R et al. Authors found that the in vitro antimicrobial efficacy of the composite against Staphylococcus aureus was comparable to existing antibiotics. While the in vitro toxicity against Candida albicans was less than the existing drug (Vazquez-Munoz et al. 2020).

Additionally, the use of commercial nanoparticles is promising. Sahar R et al. used nanoparticles (Nano Scientific Co., USA) against Enterococcus faecalis and Streptococcus salivarius. The nanoparticles had significantly greater antimicrobial activity compared to the positive control, chlorhexidine (Rostamifar et al. 2021).

The presented research suggests that such nanoparticles can be used to prevent the growth and development of bacteria in places and environments where it is not possible to treat the area with any type of radiation. One such application would be to create an antibacterial dressing to treat wounds, or to create prostheses that would reduce the risk or prevent the development of post-operative infection altogether.

Anticancer and cytotoxicity properties of bismuth nanoparticles

Bismuth nanoparticles are able to inhibit the growth of not only prokaryotic cells but also eukaryotic cells. This allows them to fight against cancer (Cheng and Zhang 2018).

Among the substances that are tested in cancer treatment are often presented bismuth sulfide, bismuth selenide, bismuth compounds with silver and other metals, and especially much bismuth oxide (Cheng and Zhang 2018; Badrigilan et al. 2020; Shahbazi-Gahrouei et al. 2023). Examples of anticancer research are presented in Fig. 2.

Fig. 2.

Fig. 2

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Anticancer properties of bismuth nanoparticles: a Bismuth nanoparticles combined with polyvinylpyrrolidone effectively stopped tumor growth in vivo under laser and X-ray exposure. Reproduced with permission (Lei et al. 2017).

Copyright 2017, Wiley–VCH. b Folate-inserted, red blood cell membrane-modified bismuth nanoparticles effectively suppressed 4T1 cells in vivo under X-ray exposure. Reproduced with permission (Deng et al. 2018). Copyright 2017, Elsevier. c Poly(vinylpyrrolidone)- and selenocysteine-modified Bi2Se3 nanoparticles suppressed tumor growth in vivo and also helped to reduce the side effects of radiotherapy due to selenium. Reproduced with permission (Du et al. 2017). Copyright 2017, Wiley–VCH. d Bi2Se3 nanoparticles modified with a free radical generator (AIPH) almost completely suppressed the growth of cancer cells, but this effect was only observed under the NIR laser. Open access (Li et al. 2019a)

Anticancer and cytotoxicity properties of bismuth nanoparticles under NIR irradiation

In the study of bismuth nanoparticles for cytotoxicity, IR laser is used because light at longer wavelengths is able to penetrate deeper into tissues and thus deliver more energy (Meesters et al. 2014; Ash et al. 2017).

Shengwu W. et al. found that AgBiS2 nanoparticles are marginally toxic to NIH/3T3 (mouse embryo fibroblast) cells in the absence of additional exposure (Wen et al. 2021). Similar results were obtained by Lei P et al. It was found that a composite of bismuth and poly(vinyl pyrrolidone) (PVP) nanoparticles was not toxic to U14 cells (mouse cervical carcinoma) without additional exposure. However, in an in vivo experiment, it was found that the composite completely suppressed tumor growth in the body when used in conjunction with IR radiation (Lei et al. 2017).

Also, Liu C et al. investigated composites of bismuth nanoparticles and gelatin, bovine and human serum albumin and found that the composite was non-toxic to HepG-2 (human liver carcinoma) and HeLa (human cervical adenocarcinoma) cell Lines without radiation. However, with IR irradiation, the composite reduced cell survival by more than 90% (Liu et al. 2020).

The study of bismuth nanoparticles in the formation of non-oxygen radicals was investigated by Xiaomin Li et al. The interaction of Bi2Se3, AIPH (2,2′-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride) and IR laser against HepG2 (human liver carcinoma) cells had a photo-thermal effect and also induced the formation of free non-oxygen radicals (Li et al. 2019a).

Moreover, there are studies in which nanoparticles are placed in structures that have selectivity to tumors. Ren et al. investigated bismuth nanoparticles coated on the membranes of CT26 (mouse carcinoma fibroblast) cancer cells. In an in vitro experiment the composite had better absorption to cancer cells than the nanoparticles alone. And under IR irradiation, the composite almost completely killed all cancer cells. In an in vivo experiment, it was discovered that the composite was able to linger longer in the bloodstream, and accumulate better in the tumor than the nanoparticles by themselves (Ren et al. 2021).

Most articles report that the mechanisms of anti-cancer activity in the case of IR are heat generation and induction of ROS formation. However, as already shown in Xiaomin Li et al., some nanoparticles are also capable of forming non-oxygen radicals, also toxic to cells.

Anticancer and cytotoxicity properties of bismuth nanoparticles under X-ray irradiation

X-Ray irradiation is widely used in cancer therapy because it suppresses the growth of cancer cells and induces their apoptosis (De Ruysscher et al. 2019).

Junjie et al. also investigated bismuth nanoparticles coated with a special composite. It was found that bismuth nanoparticles were not toxic to 4T1 cells, but when the composite of erythrocyte membranes and folate was used, as well as X-ray irradiation, the cell survival rate decreased dramatically. The composite was highly cytotoxic in an in vivo experiment (Deng et al. 2018).

Similar results were obtained by Zulkifli et al. It was discovered that the Bi2O3 nanoparticles they synthesized in two sizes (60 and 90 nm) were non-toxic to MCF-7 (human breast adenocarcinoma) cell Line. However, when exposed to X-rays, the cell survival rate dropped rapidly, especially in the sample with 60 nm size nanoparticles (Zulkifli et al. 2018). Bismuth oxide was also studied by Stewart, C et al.: Bi2O3 nanoparticles and their interaction with X-ray irradiation were investigated on the 9L (rat gliosarcoma fibroblast) cell line in vitro. Irradiation reduced cell survival on its own, but the addition of nanoparticles to cell culture significantly enhanced the effect of radiotherapy and more cancer cells were killed (Stewart et al. 2016). In addition, Sisin N et al. investigated the combined cancer therapy with Bi2O3 nanoparticles, cisplatin and irradiation. Authors found that the nanoparticles were not toxic by themselves, but in the presence of cisplatin and irradiation significantly reduced the survival of MCF-7 (human breast adenocarcinoma) and MDA-MB-231 (human breast adenocarcinoma) cells. However, against NIH/3T3 (mouse embryo fibroblast) cells, the anti-cancer effect of triple therapy was weaker (Sisin et al. 2019).

In addition, it is possible to use nanoparticles in combination with drug-delivery systems. Thus, Faghfoori M et al. synthesized a composite based on nanoparticles of bismuth, bovine albumin and methotrexate and conducted an in vitro experiment on SW480 (human adenocarcinoma epithelial) cells. The study found that bismuth nanoparticles with albumin, and with albumin and methotrexate were insignificantly toxic to cells in the absence of irradiation, but when exposed to X-rays, the survival of SW480 cells was dramatically reduced (Faghfoori et al. 2020).

These studies suggest that some bismuth nanoparticles are not toxic to cancer cells by themselves and exhibit anti-cancer properties when interacting with X-rays.

Anticancer and cytotoxicity properties of bismuth nanoparticles under both NIR and X-ray irradiation

Radiotherapy is a popular method of cancer control, but it can cause a variety of side effects (Mohan et al. 2019).

Therefore, Du et al. investigated a composite based on Bi2Se3 nanoparticles and poly(vinyl pyrrolidone) modified with the amino acid selenocysteine. It was discovered that when combined with photo and radiotherapy, the composites significantly inhibited cancer tumor growth in vivo, rapidly reducing its volume to almost 0. Moreover, trace amounts of selenium were found to enter the bloodstream when the nanocomposites decompose, improving immune function and reducing the side effects of radiation throughout the body (Du et al. 2017).

Unfortunately, there are few such studies on nanoparticle-mediated elimination of radiotherapy side effects, so more research is needed in this area.

Anticancer and cytotoxicity properties of bismuth nanoparticles without irradiation

However, there are also nanoparticles that are toxic on their own, in the absence of any irradiation.

For example, Cabral-Romero C et al. investigated the anti-cancer abilities of BiBal nanoparticles (a composite of bismuth and 2,3-dimercapto-1-propanol) on HCT-116 (human epithelial carcinoma), HeLa (human cervical adenocarcinoma), DU145 (human prostate carcinoma), and LL47 (MaDo—a non-cancerous line, human lung fibroblast). The nanoparticles embedded in a carbopol-based hydrogel had high in vitro anticancer activity against cancer lines, and the LL47 line was less sensitive to BiBal nanoparticles (Cabral-Romero et al. 2020).

Commercial bismuth oxide nanoparticles are also known to have anti-cancer activity. Ali A. et al. investigated Bi2O3 particles from Thermo Fisher Life Technologies, USA on MCF-7 (human breast adenocarcinoma) Line. The nanoparticles significantly reduced cell survival, below 30%, and also induced ROS formation (Alamer et al. 2020). Similar results were obtained by Ahamed M. et al. when studying Bi2O3 nanoparticles from Sigma Aldrich, USA, also on MCF-7 cell Line. It was found that nanoparticles significantly reduced cell survival rate, below 40%, and induced ROS formation. Moreover, the researchers explored possible mechanisms for the anti-cancer activity of nanoparticles (Ahamed et al. 2019).

A potentially good composite in the treatment of cancer is one that will destroy mutated cells under the influence of some irradiation, but has low toxicity itself, so as not to damage healthy cells throughout the body.

Mechanism of antimicrobial and anticancer activity of bismuth nanoparticles

The two main mechanisms of antimicrobial and anticancer activity of bismuth nanoparticles are ROS formation and photo-thermal effect that have been observed in studies of both bacteria and cancer cell lines.

ROS formation is achieved due to the interaction of electrons from bismuth nanoparticles with molecular oxygen of the medium under the influence of NIR irradiation (or other type of irradiation). This is connected with the transition of electrons to a new energy level.

When nanoparticles are exposed to light, electrons absorb energy and move from the valence zone to the conduction zone, electron–hole pairs are formed. In the place of electrons accumulation, a reduction site is formed, where ROS is produced as a result of interaction between electrons and molecular oxygen. And the accumulation of holes forms an oxidation site, which is involved in the damage to cell walls and membranes of bacteria.

Depending on the combination of substances (in the case of two materials), several types of mechanisms are distinguished. The energy zones of the two substances may be approximately equal, with the forbidden zone of one substance being smaller (type I); the energy zones may be slightly displaced relative to each other (type II); or significantly displaced so that the conduction zone of one substance coincides with the valence zone of the other (type III) (Fig. 3). The second mechanism is the most efficient since electrons in conduction band (CB) and holes in valence band (VB) accumulate better, which increases the redox properties of the particles. However, an even more efficient z-scheme of the system has now been developed, where electron–hole pairs are formed in a substance with a lower energy zone and then the electrons transfer to the VB and then to the CB of the second substance. In the case of three materials or more, more complex mechanisms are involved (Kumar et al. 2021).

Fig. 3.

Fig. 3

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a Energy zones in three types of mechanisms of transition of electrons. The energy bands of two substances may be approximately equal, with the forbidden band of one substance being smaller (type I); the energy bands may be slightly offset relative to each other (type II); or significantly offset, so that the conduction band of one substance coincides with the valence band of the other (type III). Electron migration in b type II mechanism and c z-scheme. Reproduced with permission (Kumar et al. 2020)

Copyright 2020, Elsevier

A typical type II mechanism was observed in the case of AgVO3/BiO2-X nanoparticles. When exposed to sunlight, electrons transfer to the conduction band in BiO2-X. The conduction potential is − 0.46 eV and the standard O2/*O2- potential is − 0.33 eV, so the BiO2-X potential and the concentrated electrons are able to capture molecular oxygen and convert it into *O2-. AgVO3/BiO2-X nanoparticles possessed greater redox capabilities than BiO2-X nanoparticles and were more efficient in forming ROS (Wang et al. 2021).

A similar system was observed in the case of gold rods coated with Bi2S3. Under IR irradiation, the electrons in bismuth sulfide move from the valence band to the conduction band and from there migrate to gold. The electrons accumulated in gold react with the surrounding O2 to form the radical *O2-, and the holes localized in Bi2S3 react with OH- to form the radical *OH. Thus, two types of ROS are formed at once (Wang et al. 2020).

Similarly, in the case of the combination of Bi2S3 and Ti3C2Tx under NIR irradiation, electrons transferred from the CB of Bi2S3 to the CB of Ti3C2Tx, where they accumulated and interacted with oxygen (Li et al. 2021b).

Type I mechanism was observed in the case of CN-Zn/Bi2S3 nanoparticles. Under IR irradiation, electron–hole pairs were formed in CN-Zn particles and then the electrons transferred to CB Bi2S3 where ROS were formed (Li et al. 2019b).

Thus, the formation of ROS occurs due to the separation of electrons and holes in the particles under the influence of irradiation. Parallel to the redistribution of electrons, a large amount of heat is generated by the transition of electrons from a high energy level to a low energy level (during the transition from the CB of one substance to the CB of another substance). However, the mechanism of ROS formation by bismuth nanoparticles without irradiation is still insufficiently studied, and additional research is required.

Use of radiation in combination with nanoparticles

Nanoparticles often exhibit their unique antimicrobial and anticancer properties only when exposed to radiation: NIR laser or X-rays. In experiments on cell lines and animal models, this combination shows significant positive results. However, the use of radiation on humans can present certain difficulties.

In particular, the use of NIR lasers raises a number of issues that must be taken into account when planning the clinical use of nanoparticles and lasers. One of the significant problems is the localization of nanoparticles in the body: they must be concentrated as much as possible in the tumor area, in the case of oncology, or in the area infected with bacteria. Otherwise, the generation of heat and ROS will be insufficient for effective therapy. Therefore, the modification of nanoparticles for targeted delivery is considered a promising direction. Another important problem is pain when using a laser. Particles can heat up to 50 degrees Celsius or more, which can cause pain and burns to healthy tissue. The main approaches to solving this problem are real-time monitoring of the patient’s condition and the use of anesthesia. However, the latter has its own difficulties in terms of tolerability and dosage. In addition, there is a problem with radiation penetration. Although IR radiation penetrates deeper than other types of radiation, sometimes this is not enough if the center of infection or cancer is located deep within the body. This is also complicated by the characteristics of the patient’s body and skin color. To increase penetration, invasive techniques such as fiber optics are suggested, but any additional surgical invasion can have a negative effect on the patient (Salimi et al. 2022) (Zhang et al. 2024).

When using X-ray radiation, a similar problem arises in terms of the complexity of localizing and targeting the delivery of particles. Although X-rays penetrate deeper than NIR lasers, it is still necessary to ensure the accumulation of nanoparticles in tumors for effective therapy. Other problems also arise, such as the oxygen-poor environment of the tumor, which hinders the active formation of ROS and reduces the effectiveness of treatment. In addition, X-rays must be used with caution as high doses of radiation can negatively affect DNA and RNA, leading to long-term side effects that may not always be apparent in preclinical and clinical studies (Liu et al. 2024) (Chen et al. 2025).

Thus, the use of radiation in combination with nanoparticles requires the resolution of important issues. A promising direction would be the development of nanoparticles that not only effectively suppress the growth of bacteria or cancer cells, but also reduce the side effects of using NIR lasers and X-rays.

Conclusion

Bismuth nanoparticles can be a promising replacement for antibiotics as they have a strong antibacterial effect when interacting with IR, solar or X-ray irradiation and in its absence both in vivo and in vitro. Bismuth nanoparticles show high antibacterial properties against common pathogenic strains, such as Escherichia coli and Staphylococcus aureus. In addition, bismuth nanoparticles show strong anti-cancer properties both in the presence of irradiation (IR or X-ray) and by themselves. However, there is selective cytotoxicity against cancer cells. Nevertheless, much research is still needed in this field to develop an effective anti-cancer drug based on bismuth nanoparticles.

Acknowledgements

This research was supported by the NRC «Kurchatov Institute» – PNPI – IMC (№124013000726-6).

Author contributions

Shaikenov R.O.: Writing–original draft, Conceptualization. Garkushina I.S.: Conceptualization, Writing–review & editing, Project administration, Supervision.

Data availability

Data will be made available on request.

Declarations

Conflict of interest

All authors declare no conflict of interests.

References

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