Photothermal Applications of Nanoparticles

Gold and silver nanoparticles are commonly selected for photothermal applications due to the ability to controllably vary the optical properties through the visible and near-infrared (NIR) regions of the spectrum to overlap with common laser wavelengths by changing particle size and shape. The figure below shows the range across which the plasmon resonance of different nanomaterials can be tuned.

The environment that the particles will be exposed to is an important consideration for maintaining the stability of the particles and optical properties over a required time period. Gold-based nanoparticles are generally more inert over a wider range of solution conditions compared with silver-based nanoparticles. Silver particles may etch rapidly when exposed to salt or low-pH environments, resulting in undesirable changes to the particle optical properties or release of free silver ions if coatings around the particles are not used to enhance stability. For these reasons, silver nanomaterials are typically selected for topical applications, while gold nanomaterials may be used for both injectable and topical treatments.

In addition to overall tuning of the plasmon resonance wavelength based on morphology and composition, the wavelength-dependent scattering and absorption responses of particles can also be tuned. The figure on the left below shows the total extinction (scattering + absorption) measured for a solution of gold nanoshells. The figure on the right shows the calculated extinction for a solution of gold nanoshells, along with the calculated scattering and absorption components that make up the total extinction.

In photothermal applications, the absorption component of the optical properties contributes to the conversion of light energy into heat energy. The scattering contribution can assist in distributing light energy throughout a region, effectively increasing the pathlength of light through a sample, and providing more opportunities for absorption to take place. We can help fine-tune nanoparticle optical properties to increase efficiency in particular applications.

Implementing nanoparticles for photothermal applications requires the selection of not only the appropriate particle size, shape, and metal type but also the appropriate surface chemistry and targeting ligands. At nanoComposix, we can modify the surface of many nanoparticles with specific functional groups, biocompatible polymers, inorganic coatings, and biomolecules (proteins, antibodies, oligonucleotides). The table below summarizes some of the most common surface modifications employed by nanoComposix for photothermal applications.

	Polyethylene glycol (PEG) ligands offer a high degree of biocompatibility, can improve stability in high salt environments, and reduce non-specific interactions. PEG ligands can be covalently bound to the metal surface to produce stable coatings.
	Silica shells act as partial barrier between the core particle and surrounding environment, providing compatibility with a wide range of solvents and improving thermal stability. The silica surface is easily modified to introduce functional groups or polymers on the surface or to attach targeting biomolecules.
	Antibodies, peptides, oligos and other targeting biomolecules can be attached to many metal nanoparticle surfaces by physisorption (passive conjugation) or covalent attachments (EDC/NHS chemistry, click reagents, or other coupling methods).

Nanoparticle-based hyperthermia is a therapeutic approach in which nanoparticles are locally or systemically administered and then activated by an external energy source to generate heat, causing selective damage to nearby tumor cells or tissues. In combination with surgery, radiotherapy, or chemotherapy, hyperthermia is an effective adjuvant therapy for cancer.

The use of metal nanoparticles can provide some advantages compared to conventional approaches. The passivation of metal nanoparticles with biocompatible surfaces such as polyethylene glycol (PEG) can achieve long circulation times, allowing accumulation of particles in tumors via the enhanced permeability and retention (EPR) effect, or by functionalizing the particles with cancer-targeting molecules. Because gold is inert and nonreactive with biological tissues, there is a lower concern regarding toxicity of gold nanoparticles compared with some other therapeutic agents, though clinical trials and studies are ongoing to continue to understand potential risks. Additionally, the absorption cross-section of nanoparticles can be orders of magnitude larger than organic dye molecules that may be used for absorption, further increasing the efficacy of the particles in absorbing light and converting to heat.

References

• Hirsch, Leon R., et al. "Nanoshell-mediated near-infrared thermal therapy of tumors under magnetic resonance guidance." Proceedings of the National Academy of Sciences, 2003, 100(23), 13549-13554.
• Riley, Rachel S., and Emily S. Day. "Gold nanoparticle‐mediated photothermal therapy: applications and opportunities for multimodal cancer treatment." Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology, 2017, 9(4), e1449.
• Mendes, Rita, et al. "Photothermal enhancement of chemotherapy in breast cancer by visible irradiation of gold nanoparticles." Scientific Reports, 2017, 7(1), 10872.
• Singh, Priyanka, et al. "Gold nanoparticles in diagnostics and therapeutics for human cancer." International Journal of Molecular Sciences, 2018, 19(7), 1979.
• Chatterjee, Dev Kumar, Parmeswaran Diagaradjane, and Sunil Krishnan. "Nanoparticle-mediated hyperthermia in cancer therapy." Therapeutic Delivery, 2011, 2(8), 1001-1014.

Nanoparticles can be functionalized and loaded with active pharmaceutical ingredients (APIs), acting as promising nanocarriers for targeted delivery of drugs or genes. The payload of such systems can be released in the designated location through plasmonic heat generation following irradiation by near-infrared (NIR) radiation, enabling another format of photothermal therapy. With the ability to be decorated and/or loaded with a variety of compounds including doxorubicin, hyaluronic acid, folate, polymers (polyethylene glycol, poly(N-isopropylacrylamide), proteins (ovalbumin, biotin) and DNA and RNA (siRNA and shRNA), gold nanoparticles provide a versatile platform for delivering therapeutic cargos.

References

1. Liu, Ji, et al. "Gold nanorods coated with mesoporous silica shell as drug delivery system for remote near-infrared light‐activated release and potential phototherapy." Small, 2015, 11(19), 2323-2332.
2. Kawano, Takahito, et al. "PNIPAM gel-coated gold nanorods for targeted delivery responding to a near-infrared laser." Bioconjugate Chemistry, 2009, 20(2), 209-212.

Gold and silver nanoparticles have been used in photothermal therapies targeting the treatment of skin cancer and other skin conditions such as rosacea and acne, along with other dermatology applications related to hair removal or liposuction. For topical applications, both gold and silver-based nanoparticles may be used, while gold-based particles are typically only used for in vivo applications.

Topical formulations containing gold or silver nanoparticles have been used in similar ways to treat acne and to improve the efficacy of laser hair removal. In both applications, a gel containing nanoparticles with tuned optical absorption is applied to the skin and ultrasonic energy is used to drive the particles into the pores. Heating of the nanoparticles in the pores can cause targeted heating and damage to the sebaceous gland to reduce the production of sebum that can cause acne or can similarly cause damage to the follicle for the removal of unwanted hair. The surface functionalization, size, and composition of the nanoparticles are critical for obtaining efficient penetration into the pores and for the efficacy of the treatment.

Local heating caused by gold nanoparticles injected into fat tissue has also been shown to improve the efficiency of liposuction procedures, with the potential to improve patient recovery time.

References

1. Paithankar, Dilip, et al. "Ultrasonic delivery of silica–gold nanoshells for photothermolysis of sebaceous glands in humans: Nanotechnology from the bench to clinic." Journal of Controlled Release, 2015, 206, 30-36.
2. Friedman, Nethanel, et al. "Physical properties of gold nanoparticles affect skin penetration via hair follicles." Nanomedicine: Nanotechnology, Biology and Medicine, 2021, 36, 102414.
3. Sheng, Wangzhong, et al. "A Single-Blind Study Evaluating the Efficacy of Gold Nanoparticle Photothermal-Assisted Liposuction in an Ex Vivo Human Tissue Model." Aesthetic Surgery Journal, 2018, 38(11), 1213-1224.

Cryopreservation allows viable cells and tissues to be preserved over time in a frozen, vitrified (glassy) state. During the transition between biological temperatures and cryogenic temperatures, the formation of ice within cells is generally lethal – both cooling and heating rates must be rapid enough to avoid the formation of ice crystals. While the injection of cryoprotectant agents can reduce the formation of ice, additional approaches may be needed to increase the cryopreservation success rate.

One example of where additional approaches are needed is in the preservation of relatively large aquatic embryos, for example for the genetic banking of embryos for research use or aquaculture. A collaboration between nanoComposix and Professor John Bischof from University of Minnesota showed that gold nanorods can be successfully used as a platform for cryopreservation of zebrafish embryos, where the large size limits the application of external convective heating during the rewarming process. The injection of biocompatible gold nanorods into the embryos prior to freezing allowed an external laser to rapidly heat the frozen embryos from within, significantly increasing the survival rate and producing embryos that develop into normal adult fish.

This technology has broad implications as a platform technology to preserve germplasm of many vertebrate and nonvertebrate systems. and may be adapted to larger cell and small tissue systems. The ability to preserve such germplasm will provide an important tool for preserving the biodiversity of the planet while also maintaining important genetic research models.

References

1. Khosla, Kanav, et al. "Gold nanorod induced warming of embryos from the cryogenic state enhances viability." ACS Nano, 2017, 11(8), 7869-7878.
2. Daly, Jonathan, et al. "Successful cryopreservation of coral larvae using vitrification and laser warming." Scientific Reports, 2018, 8(1), 15714.

While nanoparticle heating can be used to selectively induce localized damage to nearby tissues for hyperthermia applications, plasmonic nanoparticles may also be used for in situ bulk heating of particle dispersions. This property may be used, for example, to overcome the relatively slow thermocycling time that can limit the throughput of conventional polymerase chain reaction (PCR) techniques that use bulky block heaters. PCR carried out in combination with LED or laser irradiation of nanoparticle solutions has been shown to significantly reduce the time associated with each heating step, improving the DNA amplification rate. The incorporation of nanoparticles into amplification steps and other assays may improve portability and increase throughput of a variety of point-of-care applications.

References

1. Blumenfeld, Nicole R., et al. "Multiplexed reverse-transcriptase quantitative polymerase chain reaction using plasmonic nanoparticles for point-of-care COVID-19 diagnosis." Nature Nanotechnology, 2022, 17(9), 984-992.
2. Cheong, Jiyong, et al. "Fast detection of SARS-CoV-2 RNA via the integration of plasmonic thermocycling and fluorescence detection in a portable device." Nature Biomedical Engineering, 2020, 4(12), 1159-1167.