Advances and Perspectives on Bioelectronic and Atomic Nanogenerators for Anticancer Therapy
Abstract
:1. Introduction
2. Unconventional Strategies for Anti-Cancer Therapy
2.1. Localised Drug Delivery (LDD)
2.2. Photodynamic Therapy (PDT)
2.3. Sonodynamic Therapy (SDT)
2.4. Electrical Stimulation Therapy (EST)
2.5. Nanoparticle-Based Therapy (NPT)
2.6. Targeted Alpha Therapy (TAT) and Atomic Nanogenerators (ANGs)
2.7. Photoactivatable Atomic Nanogenerators (PhANGs)
3. Bioelectronic Nanogenerators for Anti-Cancer Therapy
3.1. Bioelectronic Nanogenerators (BNGs): Materials and Mechanisms
3.1.1. Piezoelectric Materials and Nanogenerators
3.1.2. Triboelectric Materials and Nanogenerators
3.1.3. Pyroelectric Materials and Nanogenerators
3.2. BNGs for Localised Anti-Cancer Drug Delivery
3.3. BNGs for Photodynamic Anti-Cancer Therapy
3.4. BNGs for Sonodynamic Anti-Cancer Therapy
3.5. BNGs for Cancer Treatment Through Bioelectrical Stimulation
4. Conclusions: Challenges and Outlook
4.1. Material Limitations
4.2. Size Requirements
4.3. Power Management Challenges
4.4. Reliability and Durability
4.5. Integration with Existing Therapies
4.6. Regulatory Hurdles
4.7. Cost-Effectiveness
4.8. Biocompatibility Issues
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Type of Device/Approach | Working Principle | Materials | Stage of Research | Ref. | |
---|---|---|---|---|---|
LOCALISED DRUG DELIVERY | Biodegradable TNG connected to an interdigitated electrode | The TNG is used as the power source to stimulate the electric field to increase the speed of the drug delivery system release of doxorubicin (DOX) from RBCs, facilitating the precise killing of cancer cells, and the DOX release rate returns to normal after the applied field is stopped. | PLA, Reed film, Mg Rice paper, gingko biloba | Device scale In vivo | [276] |
Magnet TNG in a drug delivery system | The contacting-mode TNG can ensure high and consistent electricity for enhancing the release of DOX from RBCs. | PTFE, PDMS, magnet, Cu, Ti | Device scale In vivo | [281] | |
Disk TNG within a self-powered drug delivery system | The disk-shaped TNG provides a current source for the self-powered drug delivery system and electrically stimulates cells seeded in the gap between the electrodes, facilitating also the uptake of DOX from cancer cells. | PMMA, polyamide, PVDF, Cr/Ag, Au | Device scale In vitro | [309] | |
Implantable, biodegradable, wireless TNG | With the excitation of ultrasound to the TNG, it can generate an alternating current voltage and concurrently release the loaded anti-mitotic drugs into tumor tissues, which synergistically disrupts the assembly of microtubules and filament actins, induces cell cycle arrest, and finally enhances cell death. The drug carrier incorporated into the TNG is based on carbonaceous metal-organic framework zeolitic imidazolate framework-8 (ZIF-8) NPs. | Polycaprolactone, Mg | Device scale In vivo | [275] | |
PHOTODYNAMIC THERAPY | Fully implantable, wireless, flexible optoelectronic system | The system is capable of continuous and effective cancer treatment by fusing PDT and hyperthermia and enabling tumor size monitoring in real time. It exploits inorganic μ-LEDs that emit light with a wavelength of 624 nm, and precisely monitors the tumor size by Si phototransistor during a long-term implantation | Cu, polyimide PDMS, µLED | Device scale In vivo | [285] |
PyNG for specific mytochondria-targeting | The PyNG is used for chemo-photodynamic therapy against HepG2 malignant liver tumors. A superb ROS production and tumor cell elimination capability is disclosed via mitochondria-targeting and hypoxia-relieving performances. The PyNG, based on the heat-conducting coating of poly-dopamine, is integrated in a drug delivery system for the co-release of DOX and EGCG. | Barium titanatePoly-dopamine (PDA) | In vitro | [310] | |
Twinning structured PNG for self-powered PDT | Powered by energy harvested from body motion, the system realizes effective tumor tissue killing and inhibition. | Parylene/PET, Cu, Ag, PVDF | Device scale In vivo | [287] | |
PNG for PDT/SDT low-dose/long-term cancer treatment | Implantable self-powered therapeutic pellet that provides wireless PDT/SDT hybrid therapy for low-dose/long-term cancer recurrence inhibition and tumor regression. The miniature pellet contains an integrated self-powered unit, a light-emitting diode illuminant, and a control circuit. | Ag Polyimide | Device scale In vivo | [297] | |
PNG coupled with a self-powered wireless drug/light injector | The device comprises a semi-invasive pedestal with a micro light emitting diode (μ-LED) and a syringe needle, as well as a detachable actuator that contains a drug reservoir, a thermally-driven pump, and a wireless control circuit. The device can be wirelessly controlled to deliver on-demand dosages of drugs and light into the tumor under the skin, producing ROS species and inducing cancer cell apoptosis. | Magnet µLED | Device scale In vivo | [311] | |
SONODYNAMIC THERAPY | PNG for piezo-catalytic treatment of hypoxic tumors | The system includes acid-degradable Janus-type multicompartmental carriers able to separately encapsulate piezocatalytic Au nanoparticle-coated poly(ethylene glycol)-modified zinc oxide nanorods (Au@P-ZnO NRs) and O2-generating catalase (CAT). The sequential release by the Janus carriers significantly increased the intracellular ROS levels under hypoxia conditions upon ultrasound irradiation owing to the O2 supplied by the CAT. | Poly(ethylene glycol)ZnO Au | Device scale In vivo | [312] |
PNG based on iron-doped and oxygen-deficient piezoelectric nanosheets | Due to the existence of oxygen defects introduced through Fe doping, the bandgap of BWO-Fe is significantly narrowed so that BWO-Fe can be more easily activated by exogenous ultrasound (US). The oxygen defects acting as the electron traps inhibit the recombination of US-induced electrons and holes. More importantly, the dynamically renewed piezoelectric potential facilitates the migration of electrons and holes to the opposite side and causes energy band bending, which further promotes the production of reactive oxygen species and induces the tumor cells’ apoptosis. | Bismuth tungstate nanosheets Fe | In vivo | [313] | |
Ultrasound-activated Au/ZnO-based Trojan PNG | Firstly, the ZnO-nanogenerators will generate a piezoelectric potential difference of about 140 mV by ultrasonic excitation when targeted (by MLS moiety) to the mitochondria, disrupting the mitochondrial membrane potential for electrostimulation. Secondly, the nanogenerators enhance greatly multiple enzyme-like activities of Au nano-components for enhanced tumor catalytic therapy | ZnO, Au Poly(ethylene glycol) | In vitro | [13] | |
PNG based on ultrasonic-responsive piezoelectric NPs for treatment of glioblastoma | The remote ultrasound-mediated piezo-stimulation significantly reduced the proliferation of glioblastoma cells in vitro, and when combined with a sub-toxic concentration of temozolomide, it enhanced sensitivity to chemotherapy while producing remarkable anti-proliferative and pro-apoptotic effects. | Barium titanate | In vitro | [295] | |
Wireless, battery-free therapeutic dot for piezo-PDT | The therapeutic dot is implanted directly inside the tissue around the tumor and wirelessly controlled by ultrasound (US), allowing dual activation of electron-hole pairs from the nanocomposites via US and ultraviolet light (UV). The internally generated piezoelectric field minimizes electron-hole recombination, maximizing ROS induction within tumor cells. | Au, ZnO nanorods Poly(ethylene glycol) | In vivo | [291] | |
ELECTRICAL STIMULATION THERAPY | Human-driven TNG coupled with implantable and biodegradable nanofibrous patch | The nanofibrous patch incorporates doxorubicin (DOX) and graphitic carbon nitride (g-C3N4), in which the peroxidase (POD)-like activity of g-C3N4 to produce hydroxyl radical (•OH) can be distinctly enhanced by the self-driven electrical stimulation for 4.12-fold, and simultaneously DOX can be released to synergize the therapy. | PDMS, TiO2, Nitrile, Al Gelatin, polycaprolactone | Device scale In vivo | [8] |
Optically microprinted flexible interdigital electrode with an Au-plated polymer microneedle array | The flexible microneedle-array-integrated interdigital electrode is fabricated by combining optical 3D microprinting and electroless plating processes. Electrical stimulation of cancer cells induced necrotic cell death through mitochondrial Ca2+ overload and increased intracellular reactive oxygen species (ROS) production. This led to the release of damage-associated molecular patterns that activated the immune response and potentiated immunogenic cell death (ICD). | Au, acrylic | Device scale In vivo | [136] | |
AC stimulation electrodes in tumor cell cultures | Low frequency, low intensity alternating current electrical stimulation drastically enhances chemotherapeutic efficacy in MDR1 drug-resistant malignant tumors. | Stainless steel leads | In vitro | [299] | |
Ultrasound-activated piezoelectric nanoparticles (NPs) | Chronic piezoelectric stimulation results in the ability to inhibit cancer cell proliferation by upregulating the expression of the gene encoding Kir3.2 inward rectifier potassium channels, by interfering with Ca2+ homeostasis, and by affecting the organization of mitotic spindles during mitosis. | Barium titanate NPs | In vitro | [304] | |
Electrodes for nano-pulsed electrical stimulation | The study is conducted on a mouse malignant melanoma model. After stimulation, the number of T lymphocytes as measured in the spleen increased, indicating that the therapy stimulates the immune system of the animal to attack the tumor. | Metal leads | In vivo | [314] | |
NANOPARTICLE-BASED THERAPY | Magnetostrictive-piezoelectric triggered tumor therapy | The system initiates an intratumoral magneto-driven and piezoelectric-catalyzed reaction using core–shell structured CoFe2O4–BiFeO3 magnetostrictive-piezoelectric nanoparticles under an alternating magnetic field. The NPs catalyze the generation of (ROS), in particular superoxide radicals (•O2–) and hydroxyl radicals (•OH). | CoFe2O4–BiFeO3 | In vivo | [315] |
Piezoelectric oral microrobots for targeted catalytic and immunotherapy of colorectal cancer | The microrobots consist of Veillonella atypica (VA) cells whose surface is loaded with Staphylococcus aureus cell membrane–coating BaTiO3 nanocubes via click chemical reaction. Following oral administration, the microrobots accurately targeted orthotopic colorectal cancer. Under in vitro ultrasonic stimulation, the piezoelectric particles catalyze two reduction reactions (O2 → •O2− and CO2 → CO) and three oxidation reactions (H2O → •OH, GSH → GSSG, and LA → PA) simultaneously, effectively inducing immunogenic death of tumor cells. | Barium titanate NPs | Device scale In vivo | [316] | |
Janus-type nanocarriers with piezoelectric nanomaterials | The acid-degradable Janus-type multicompartmental carriers are able to separately encapsulate piezocatalytic gold nanoparticle-coated poly(ethylene glycol)-modified zinc oxide nanorods and O2-generating catalase. The sequential release by the Janus carriers significantly increased the intracellular ROS levels under hypoxia conditions upon ultrasound irradiation owing to the O2 supplied by the catalase. | Au, ZnO nanorods, Poly(ethylene glycol) | In vivo | [312] | |
Engineered NPs carrying photosensitizers | The NPs can be specifically activated within tumors by conjugating antibodies against programmed death ligand 1 (PDL1) with matrix metalloproteinase protein 2 (MMP-2)–sensitive NPs that carry a photosensitizer, ICG (MMP-2 is highly expressed in tumors). When used in conjunction with localized near-infrared radiation that activates the photosensitizer to produce ROS, the effect of limiting the growth and metastasis of murine tumors is enhanced. | αPDL1/ICG nanocomplexesEpigallocatechin-3-O-gallate (dEGCG) Poly(ethylene glycol) | In vivo | [317] | |
ATOMIC NANOGENERATORS | Liquid metal nanodroplet-based NO nanogenerator | The liquid metal nanodroplet (LMND)-based NO nanogenerator (LMND@HSG) is stabilized by a bioreducible guanylated hyperbranched poly(amido amine) (HSG) ligand. Mechanically, the tumor microenvironment specifically triggers a cascade process of glutathione elimination, ROS generation, and NO release. | EGaIn | In vivo | [318] |
Calcium phosphate ANG for NO production | The calcium phosphate nanotheranostic system (GCAH) is constructed for effective synergistic cancer starvation/gas therapy and it is obtained by a facile biomineralization strategy using glucose oxidase (GOx) as a biotemplate, followed by loading of l-Arginine (L-Arg) and modification of hyaluronic acid (HA) to allow special selectivity for glycoprotein CD44 overexpressed cancer cells. The system only exhausts the glucose nutrients in tumor region by the GOx-triggered glucose oxidation, while the generated H2O2 can oxidize L-Arg into NO under acidic tumor microenvironment for enhanced gas therapy. | Calcium phosphate | In vivo | [319] | |
Ultrasound and laser-promoted dual-gas ANG | In this nanogenerator, calcium carbonate–polydopamine–manganese oxide NPs undergo reactive decomposition in a moderately acidic tumor, resulting in the generation of calcium, manganese ions, carbon dioxide (CO2), and oxygen (O2). Calcium and manganese ions act as adjuvants that trigger an immune response. The cancer cell membrane rupture caused by sudden bursts of bubbles (CO2 and O2) under ultrasound stimulation and the photothermal properties of polydopamine also contributed to the anti-tumor effect. | Calcium carbonate Polydopamine Manganese oxide | In vivo | [320] | |
ANG for Ca2+ production | The ANG is based on calcium phosphate (CaP)-doped hollow mesoporous copper sulfide. This generates Ca2+ directly and persistently in the lysosomes (low pH). Near-infrared light radiation can accelerate Ca2+ generation from the basic Ca2+ nanogenerator by disturbing the crystal lattice of hollow mesoporous copper sulfide via NIR-induced heat. Curcumin can facilitate Ca2+ release from the endoplasmic reticulum to the cytoplasm and inhibit the expelling of Ca2+ in the cytoplasm through the cytoplasmic membrane. | Calcium phosphate-doped hoped mesoporous copper sulfide | In vivo | [321] |
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Mariello, M. Advances and Perspectives on Bioelectronic and Atomic Nanogenerators for Anticancer Therapy. Nanoenergy Adv. 2025, 5, 4. https://doi.org/10.3390/nanoenergyadv5020004
Mariello M. Advances and Perspectives on Bioelectronic and Atomic Nanogenerators for Anticancer Therapy. Nanoenergy Advances. 2025; 5(2):4. https://doi.org/10.3390/nanoenergyadv5020004
Chicago/Turabian StyleMariello, Massimo. 2025. "Advances and Perspectives on Bioelectronic and Atomic Nanogenerators for Anticancer Therapy" Nanoenergy Advances 5, no. 2: 4. https://doi.org/10.3390/nanoenergyadv5020004
APA StyleMariello, M. (2025). Advances and Perspectives on Bioelectronic and Atomic Nanogenerators for Anticancer Therapy. Nanoenergy Advances, 5(2), 4. https://doi.org/10.3390/nanoenergyadv5020004