Photothermal therapy (PTT) is a non-invasive treatment approach that uses photosensitizers to efficiently convert light energy into heat under near-infrared (NIR) irradiation, inducing localized temperature increases (typically 42 ℃–52 ℃) to ablate tumor cells. The integration of nanotechnology provides key photothermal transducers for PTT, such as gold nanorods, gold nanoshells, and black phosphorus nanosheets, which possess strong localized surface plasmon resonance (LSPR) or broad optical absorption bands. These nanomaterials can produce substantial thermal effects under low-intensity light, thereby improving therapeutic efficiency while reducing harm to healthy tissues.
Meanwhile, nanocarriers enable the co-delivery of drugs, genes, or immunomodulators, forming multimodal therapies that combine photothermal effects with chemotherapy or immunotherapy. This theranostic approach allows simultaneous treatment and monitoring of the therapeutic process using imaging modalities such as photoacoustic, fluorescence, or magnetic resonance imaging.
In recent years, strategies such as armored gold nanostars, composite nanoplatforms capable of real-time photoacoustic thermal monitoring, and mild photothermal therapy (mPTT) combined with immune checkpoint inhibition have demonstrated significant tumor suppression in animal models. These advances indicate that nanotechnology-driven photothermal therapy is rapidly progressing toward precise, low-side-effect cancer treatment.
The core principle behind photothermal therapy is the ability of nanomaterials to absorb light and convert it into heat. This process begins when nanoparticles are exposed to light at specific wavelengths, particularly within the near-infrared region (600–1350 nm). When light interacts with these nanoparticles, it excites electrons to higher energy levels. These excited electrons then transfer energy to the lattice structure of the nanoparticle through electron-phonon interactions, which generates heat.
Nanoparticles used in photothermal therapy employ different mechanisms for photothermal conversion, based on their material properties. Noble metal nanoparticles, such as gold nanorods, rely on surface plasmon resonance (SPR). This phenomenon occurs when the frequency of incoming light matches the collective oscillation frequency of conduction electrons in the metal, resulting in strong light absorption and scattering. Carbon-based nanomaterials, such as single-walled carbon nanotubes, utilize their sp2 hybridized carbon network structure for efficient photothermal conversion via π-π electron transitions*. Semiconductor materials, such as Ag2S quantum dots, exhibit photothermal properties that depend heavily on their band structure. Advances in band-gap engineering allow the modification of these materials to enhance their light absorption range and photothermal efficiency.
Nanoparticle-mediated heat generation offers several distinct advantages over traditional thermal therapies, especially in terms of targeting precision, treatment efficiency, and biocompatibility.
Targeted Accumulation at Tumor Sites: Nanoparticles can accumulate at tumor sites through both passive and active targeting mechanisms. Passive targeting exploits the enhanced permeability and retention (EPR) effect, a phenomenon in which the leaky vasculature of tumor tissues allows nanoparticles (typically between 20 and 200 nm in size) to accumulate more efficiently. Active targeting, on the other hand, involves surface modifications of nanoparticles with specific ligands (e.g., folic acid, peptides, or antibodies) that bind to overexpressed receptors on tumor cells, further enhancing accumulation and treatment precision.
Superior Photothermal Conversion Efficiency: Nanoparticles can exhibit exceptional photothermal conversion efficiencies and tunable optical properties. For example, NaYF4:Yb3+, Tm3+@NaYF4:Yb3+@SiO2-SWCNT composites have demonstrated a temperature increase of 36.8 ℃ in water dispersions upon exposure to 980 nm light. Additionally, protein-coated Ag2S nanoparticles have been shown to achieve a photothermal conversion efficiency of 59%, while emitting effective fluorescence in the second near-infrared window, making them ideal for combined therapeutic and imaging purposes.
Synergistic Therapy: Nanoparticles enable the integration of multiple therapeutic modalities in a single platform. For instance, a dual-layer composite nanoparticle can carry a photothermal agent, a photodynamic agent, and chemotherapeutic drugs (such as doxorubicin). This combination allows for a synergistic therapy strategy that alternates photothermal and photodynamic treatments with chemotherapy, improving tumor suppression and treatment outcomes.
The efficiency of photothermal therapy depends on several key factors that must be optimized for maximum therapeutic effect. These parameters, which interact in complex ways, include:
Light Source Parameters: The wavelength of the light source plays a crucial role in determining the therapeutic efficacy of photothermal therapy. Wavelengths must match the absorption characteristics of the nanoparticles to achieve optimal light-to-heat conversion. Most applications utilize wavelengths within the red to near-infrared spectrum (600 to 1070 nm), referred to as the "optical window," where tissue absorption and scattering are minimized, enabling deeper penetration.
Energy Density: The energy density of the light must be high enough to induce the desired therapeutic effects but not so high as to cause toxicity or adverse side effects. Recent innovations in photothermal therapy devices, such as microneedle systems, allow for deeper penetration with reduced laser power, these devices can penetrate tissues 20 times deeper than traditional lenses while requiring only one-fifth of the power to achieve the same treatment temperature.
Nanoparticle Characteristics: Several nanoparticle properties directly affect photothermal conversion efficiency:
Spatiotemporal Coordination: The overall therapeutic efficacy of photothermal therapy can be significantly influenced by the precise timing and coordination of the treatment. One promising strategy involves alternating photothermal therapy and chemotherapy in a sequential manner. For instance, a study proposed a high-intensity treatment schedule involving three rounds of photothermal therapy within the first 20 hours, followed by 28 hours of chemotherapy. This approach maximized treatment intensity while minimizing side effects by adjusting the treatment sequence.
Real-Time Temperature Monitoring: Monitoring and controlling the temperature of the treated area in real time is essential to ensure effective and safe treatment. Tumor tissues often have complex temperature distributions, and ensuring that the temperature stays within the optimal therapeutic range is critical to avoid damage to healthy tissue. Research into self-monitoring photothermal agents that combine up-conversion nanoparticles with single-walled carbon nanotubes for temperature sensing shows promise in providing precise, real-time feedback during treatment. This temperature feedback not only helps optimize therapeutic outcomes but also minimizes side effects on surrounding normal tissues.
Fig.1 Nanomaterial-mediated photothermal therapy on tumor cells1,2.
Photothermal nanomaterials can be categorized based on their composition and properties, with each type exhibiting unique photothermal conversion mechanisms and functional characteristics. Ideal photothermal nanomaterials typically combine high photothermal conversion efficiency, biocompatibility, adequate tissue penetration, and controllable surface functionalization. Among the most extensively studied are noble metal nanomaterials, carbon-based nanostructures, semiconductor nanoparticles, and magnetic nanoparticles. These materials demonstrate strong absorption in the near-infrared region, enabling efficient conversion of light energy into heat and facilitating precise photothermal applications.
Gold nanomaterials are among the most widely explored photothermal agents, with their optical properties primarily arising from localized surface plasmon resonance. When the frequency of incident light matches the collective oscillation of electrons in gold nanoparticles, strong light absorption and scattering occur.
Gold nanorods: Their plasmonic resonance can be precisely tuned by adjusting the aspect ratio, allowing peak absorption in the NIR region. Gold nanorods can rapidly elevate local temperatures under NIR irradiation, achieving efficient photothermal conversion.
Gold nanoshells: Composed of a dielectric core and a gold shell, the optical response of nanoshells can be tuned by modifying the core size and shell thickness. Their absorption peaks are easily shifted to the NIR range, making them suitable for deep-tissue photothermal applications.
Gold nanostars: The branched morphology generates strong local electric field enhancement at the tips, further increasing photothermal efficiency.
Surface functionalization of gold nanomaterials is straightforward, enabling the conjugation of targeting ligands such as peptides or antibodies for enhanced accumulation at specific sites. Gold-based composite nanostructures combining gold with other functional nanomaterials can also be engineered for multimodal synergistic applications.
Carbon-based nanomaterials are recognized for their excellent photothermal stability and high conversion efficiency.
Graphene and graphene oxide (GO): The sp2-hybridized two-dimensional structure exhibits broad NIR absorption. The large surface area facilitates functionalization, enabling molecular loading via π-π stacking, covalent bonds, or electrostatic interactions. GO's oxygen-containing functional groups provide good dispersibility and functionalization potential, while reduced graphene oxide (rGO) partially restores the conjugated network, enhancing photothermal performance. PEGylated GO can accumulate efficiently at target sites and produce significant heat under NIR irradiation.
Carbon nanotubes (CNTs): Both single-walled and multi-walled CNTs possess one-dimensional tubular structures with strong NIR absorption. Their aspect ratio influences cellular uptake and tissue distribution, and surface modification can improve water dispersibility and biocompatibility while preserving thermal and photostability.
The photothermal effect of carbon-based nanomaterials is driven by electron excitation and non-radiative relaxation within their conjugated networks, allowing stable and sustained heat generation without performance degradation.
Semiconductor nanomaterials: Materials such as copper sulfide, black phosphorus, and transition metal chalcogenides extend their absorption edges into the NIR region through bandgap engineering. Copper sulfide nanoparticles can generate reactive species during photothermal conversion, enabling combined photothermal-catalytic effects. Black phosphorus quantum dots feature tunable band gaps and strong NIR absorption, along with favorable degradability.
Magnetic nanoparticles: Primarily superparamagnetic iron oxide nanoparticles, these materials generate heat via magnetic hysteresis or relaxation processes under alternating magnetic fields. The size and morphology of iron oxide nanoparticles influence magnetic heating efficiency, with cubic particles typically exhibiting higher performance than spherical ones due to enhanced anisotropy. Optimized nanoparticles in the 30–40 nm range can achieve substantial heating efficiency under suitable field conditions.
BOC Sciences offers versatile nanoparticles engineered for targeted drug delivery and therapeutic applications. Our customized solutions enhance treatment efficacy and precision.
Nanoparticle-induced photothermal effects rely on the intricate interplay of photophysical and photochemical processes, enabling precise ablation of target cells. When nanoparticles are irradiated with light of specific wavelengths, energy is absorbed, converted, and ultimately released as heat at levels sufficient to disrupt cellular structures. Understanding these mechanisms is crucial for optimizing photothermal performance and guiding the design of advanced nanomaterials. The photothermal efficiency of nanoparticles is influenced not only by their material composition but also by size, morphology, surface chemistry, and the surrounding microenvironment.
Light absorption: Governs photothermal efficiency. Different types of nanoparticles absorb photons through distinct mechanisms. Noble metal nanoparticles primarily rely on localized surface plasmon resonance, carbon-based materials absorb light through electronic transitions within conjugated structures, and semiconductor nanoparticles utilize bandgap excitation. These absorption mechanisms determine the intensity and spectral range at which nanoparticles can effectively harvest light energy.
Localized surface plasmon resonance: Mechanism in noble metals. In noble metal nanoparticles, when the incident light frequency matches the collective oscillation frequency of free electrons, strong resonance absorption occurs. Nanostructures such as gold nanorods and nanoshells can be engineered to shift their plasmon resonance into the near-infrared region, taking advantage of the optical transparency window of biological media for deeper light penetration.
Heat dissipation: Mechanisms and influencing factors. After photon absorption, the energy of excited electrons is transferred to the nanoparticle lattice through electron–phonon coupling, rapidly raising the particle temperature on picosecond to nanosecond timescales. Heat subsequently diffuses into the surrounding environment primarily through phonon–phonon interactions. Heat transfer efficiency depends on nanoparticle surface chemistry, thermal conductivity of the local medium, and interfacial resistance between the particle and surrounding biomolecules. Surface functionalization can improve thermal contact, while nanoparticle aggregation can modulate heat dissipation pathways, sometimes producing synergistic enhancement of the photothermal effect.
Thermal effects: Drive cellular damage. Local temperature elevations to 40–45 ℃ induce heat stress responses in target cells, including protein denaturation and altered membrane fluidity. Further increases to 45–50 ℃ result in membrane disruption and enzyme inactivation, while temperatures above 50 ℃ trigger rapid coagulative cell death. These thermal effects involve molecular events such as heat shock protein upregulation, cytoskeletal remodeling, and collapse of mitochondrial membrane potential, ultimately activating intrinsic cell death pathways and DNA fragmentation. Short-duration high-temperature exposure has been found to be more effective than prolonged moderate heating in triggering cellular demise.
Reactive oxygen species: Contribute synergistically. Many nanoparticles generate ROS upon light excitation, including singlet oxygen, superoxide, and hydroxyl radicals. These reactive species induce oxidative stress, damaging lipids, proteins, and nucleic acids.
Thermal stress and ROS act synergistically: heat increases cell susceptibility to oxidative stress, while ROS amplify thermal-induced cytotoxicity. Certain nanomaterials, such as copper sulfide or iron oxide, possess enzyme-like activity that catalyzes the decomposition of endogenous hydrogen peroxide, further enhancing oxidative damage.
Synergy with chemotherapy: Photothermal heating can increase vascular permeability and tissue perfusion, improving nanoparticle-mediated drug accumulation. Elevated temperatures also enhance membrane fluidity, promoting cellular uptake of chemotherapeutics, and can suppress drug efflux proteins. For example, drug-loaded gold nanorods under near-infrared irradiation have demonstrated tumor growth inhibition significantly higher than either therapy alone. Heat-responsive drug release systems enable spatially and temporally controlled delivery, minimizing systemic exposure.
Synergy with photodynamic therapy: Photothermal effects can alleviate hypoxic conditions, enhancing oxygen-dependent cytotoxicity in PDT. Conversely, ROS generated during PDT compromise cellular antioxidant defenses, increasing susceptibility to heat-induced damage. Multifunctional nanoparticles can achieve sequential photothermal–photodynamic activation: the inner core generates heat to modulate the local environment, followed by outer-shell ROS production. This staged activation strategy improves therapeutic efficiency while reducing off-target effects.
Enhancing the photothermal conversion efficiency of nanoparticles is critical for optimizing their performance in photothermal applications. Strategic material design and structural modulation can significantly improve light absorption, heat generation, and tumor-targeting specificity, enabling effective treatment at reduced light intensity.
Surface functionalization is a key approach to improving nanoparticle biodistribution and target specificity. By decorating nanoparticles with specific targeting ligands, such as peptides, antibodies, or polysaccharides, nanoparticles can preferentially accumulate at the intended site, enhancing local concentration while minimizing off-target interactions.
For example, peptide-drug conjugates incorporating biotin or other targeting moieties can exploit enhanced permeability and retention effects alongside active recognition mechanisms, promoting efficient cellular uptake. The inclusion of targeting ligands not only increases accumulation in diseased regions but also mitigates nonspecific distribution in healthy tissues, thereby enhancing system-level safety.
Surface functionalization also improves colloidal stability and biocompatibility. Biomolecule-based coatings, such as keratin-capped gold nanoparticles, enhance dispersion in aqueous media while providing bioinspired surfaces that reduce cytotoxicity compared with conventional citrate or surfactant-capped nanoparticles. Such functionalization extends circulation half-life and enables improved interaction with the biological microenvironment.
The biocompatibility and structural stability of nanoparticles are essential for their translational potential. Ideal nanoparticles maintain stability under physiological conditions and can be metabolized or degraded after completing their intended function, avoiding long-term accumulation.
Carbon quantum dots (CDs), typically below 10 nm in size, demonstrate excellent biocompatibility and renal clearance potential, reducing accumulation in the reticuloendothelial system. Composite systems such as CDs-ICG@BSA combine carbon quantum dots with indocyanine green and bovine serum albumin, achieving high photothermal conversion efficiency (approximately 61%) alongside excellent aqueous solubility and minimal toxicity.
Photostability is another critical factor. Many organic photothermal agents, such as ICG, are prone to photobleaching under continuous light exposure. Hybridization with inorganic materials or incorporation into composite nanostructures can enhance stability. For instance, CDs-ICG@BSA nanoparticles maintain strong photothermal performance and minimal size, demonstrating the advantages of such a composite design.
Precise control over heat distribution and effective penetration into deep tissue are major challenges in photothermal applications. Nonuniform heating can result in incomplete ablation or damage to surrounding healthy structures.
Patterned or lattice-based irradiation approaches allow controlled spatial distribution of light, providing more uniform temperature profiles across irregularly shaped targets. This minimizes overheating of superficial or deep regions, protecting the surrounding material.
For deeper penetration, the second near-infrared window (NIR-II, 900–1880 nm) offers reduced scattering and autofluorescence, enhancing signal-to-noise ratios. Advanced systems using AIE luminogens integrated into polymeric nanofibers enable NIR-II-guided photothermal activity, facilitating precise targeting of deep or residual regions. Monte Carlo simulations can further optimize nanoparticle concentration, light power, and tissue depth to predict heating profiles, guiding design decisions during early development.
Photothermal strategies have expanded from localized ablation to modulation of the microenvironment, enabling suppression of secondary growth or metastasis. By inducing controlled cellular stress, photothermal systems can trigger the release of molecular signals that activate systemic responses, enhancing the overall efficacy of combination strategies.
Innovative approaches integrating engineered microbial systems or implantable photothermal patches offer additional advantages. For example, biodegradable polymeric nanofiber scaffolds embedded with AIE luminogens enable repeated, spatially controlled photothermal activation post-implantation. This approach ensures precise ablation of residual regions while minimizing off-target effects.
Photothermal nanoparticles also show promising applications in antibacterial and tissue engineering contexts. Biocompatible gold nanoparticles, for instance, can selectively inactivate thermosensitive microbial strains, offering new strategies for addressing drug-resistant infections.
In tissue regeneration, photothermal nanofibers act as scaffolds that mimic the extracellular matrix, supporting cell adhesion, proliferation, and migration. These multifunctional platforms not only prevent regrowth of unwanted cellular populations but also promote regeneration of healthy tissue structures.
By combining photothermal functionality with other molecular interventions, such as immunomodulatory or metabolic signaling agents, these systems offer synergistic enhancement of target responses while maintaining controlled safety profiles.
BOC Sciences provides cutting-edge nanoparticle technologies focused on photothermal therapy. Our product portfolio includes metal, carbon-based, semiconductor, and magnetic nanoparticles, offering tunable photothermal properties and excellent biocompatibility, widely applied in tumor treatment, drug delivery, and multimodal therapy. We also offer surface functionalization of nanoparticles to optimize therapeutic outcomes, catering to personalized needs.
Table 1. Nanocarriers for Drug and Gene Delivery in PTT.
| Product Category | Key Features | Application Scenarios | Inquiry |
| Metal Nanoparticles | Tunable photothermal properties, NIR absorption, deep tissue penetration | Tumor photothermal therapy, combined with chemotherapy or photodynamic therapy | Inquiry |
| Carbon-based Nanoparticles | High photothermal stability, broad NIR absorption, large surface area | Photothermal therapy, drug delivery | Inquiry |
| Semiconductor Nanoparticles | Tunable bandgap, strong photothermal conversion, degradability | Deep tissue tumor treatment, combined photothermal therapy | Inquiry |
| Magnetic Nanoparticles | Heat generation under alternating magnetic fields, magnetic-thermal synergistic therapy | Magnetic-thermal combined therapy, targeted tumor treatment | Inquiry |
| Composite Nanoplatforms | Multifunctional platforms, drug and photosensitizer loading | Multimodal therapy, combined photothermal and chemotherapy | Inquiry |
BOC Sciences offers comprehensive nanoparticle customization services, including the synthesis of metal, carbon-based, and semiconductor nanoparticles with adjustable size, shape, and photothermal properties. Our services extend to surface functionalization, photothermal performance optimization, drug delivery design, and stability/biocompatibility testing. We ensure the high efficacy and safety of our nanoparticles both in vitro and in vivo, enabling precise and effective photothermal therapy solutions.
Table 2. Advanced Nanoparticle Delivery Solutions for Photothermal Therapy.
| Service Category | Service Content | Inquiry |
| Nanoparticle Customization | Synthesis of metal, carbon-based, semiconductor nanoparticles with tunable size, shape, and photothermal properties | Inquiry |
| Surface Functionalization | Modification with ligands, antibodies, peptides to enhance targeting and biocompatibility | Inquiry |
| Photothermal Performance Optimization | Evaluation of photothermal efficiency and computational simulation to optimize treatment parameters | Inquiry |
| Drug Delivery Design | Design of thermoresponsive drug release systems for controlled release and targeted delivery | Inquiry |
| Stability/Biocompatibility Testing | In vitro and in vivo stability and biocompatibility assessments of nanoparticles | Inquiry |
Nanoparticle-assisted photothermal therapy efficiently converts light energy into heat, enabling precise localized heating of tumor tissues and providing an effective, controllable strategy for tumor ablation. The diverse design and functionalization of nanomaterials not only enhance photothermal conversion efficiency and tumor-targeting capability but also allow synergistic integration with drug delivery and multimodal therapies, further improving therapeutic outcomes. Through fine-tuned control of light source parameters, nanoparticle characteristics, and heat distribution, combined with real-time temperature monitoring and deep-tissue penetration technologies, photothermal therapy achieves high-precision tumor management while ensuring safety. Looking ahead, nanotechnology-driven photothermal platforms hold broad potential in cancer treatment and related biomedical applications, offering reliable solutions for precision medicine. Leveraging its expertise in optimizing nanoparticle properties, light parameters, and thermal profiles, BOC Sciences is advancing nanoparticle-assisted photothermal therapy toward precise, efficient tumor management and expanded biomedical applications.
References
