Photodynamic therapy (PDT) is a light-activated treatment strategy that leverages the generation of cytotoxic reactive oxygen species (ROS) within targeted cells. Its defining advantage lies in precise spatiotemporal control: the therapeutic effect occurs only within the illuminated area, minimizing off-target interactions.
The mechanistic foundation of PDT relies on a cascade of photochemical reactions. Upon absorbing photons, a photosensitizer transitions from its ground state to an excited singlet state, which then undergoes intersystem crossing to a longer-lived triplet state. In this state, the photosensitizer can engage with surrounding biomolecules via two primary pathways:
Type I reaction: Electron or proton transfer occurs with biomolecular substrates, generating superoxide anions, hydrogen peroxide, and other ROS.
Type II reaction: Energy is transferred to molecular oxygen in its triplet state, producing highly reactive singlet oxygen.
Singlet oxygen can irreversibly oxidize proteins, lipids, and nucleic acids within cells, ultimately triggering cell death. This mechanism underpins PDT's ability to selectively eliminate targeted cells while limiting collateral damage.
PDT represents a sophisticated integration of photophysics, photochemistry, and biological response. The therapeutic process can be summarized in three stages:
Photosensitizer administration: The agent is delivered either locally or systemically, followed by a defined drug-light interval to ensure sufficient accumulation in the target tissue while minimizing presence in healthy tissue.
Light activation: Illumination with a wavelength matched to the photosensitizer's absorption spectrum triggers the photochemical reactions.
ROS-mediated cellular damage: Generated ROS, particularly singlet oxygen, rapidly disrupts key cellular structures, such as mitochondrial and lysosomal membranes, activating death pathways.
Due to the extremely short lifetime of singlet oxygen (diffusion radius typically<20 nm), its cytotoxic effect is highly localized, confining therapeutic impact to the illuminated region.
The efficacy of PDT relies on the coordinated interaction of three essential elements:
Photosensitizer: Determines the treatment window and efficiency. Ideal properties include selective accumulation in target tissue, strong absorption in the visible or near-infrared range for deep tissue penetration, and high singlet oxygen quantum yield. Commonly studied compounds include porphyrin derivatives such as protoporphyrin IX and phthalocyanines.
Light source: Selected based on target depth and location. Surface lesions can be treated with lasers or LED arrays matched to the photosensitizer's absorption peak, while deeper tissues require near-infrared light or fiber-optic delivery.
Oxygen: Acts as the substrate for photochemical reactions. Insufficient oxygen concentration in the target tissue can significantly reduce ROS production and impair PDT efficiency, representing a fundamental limitation.
Conventional PDT faces several intrinsic challenges:
Nanotechnology offers effective solutions:
Enhanced solubility and stability: Encapsulation in liposomes, polymeric micelles, or dendrimers prevents aggregation and maintains photophysical activity. For example, zinc phthalocyanine loaded into PLA-PEG nanoparticles improves solubility and achieves selective accumulation via enhanced permeability and retention.
Active targeting: Surface functionalization with antibodies, peptides, or aptamers promotes selective accumulation in diseased tissues, reducing off-target exposure.
Expanded therapeutic capabilities: Nanoplatforms enable combination strategies (e.g., PDT with photothermal therapy) and allow the use of upconversion nanoparticles to convert deeply penetrating near-infrared light into visible wavelengths, activating photosensitizers that normally require visible light and extending the reach of PDT to deep tissues.
Fig.1 Tumor cell damage via nanoparticle-assisted PDT1,2.
The integration of nanoparticle systems has significantly advanced the capabilities of PDT by addressing several key limitations of conventional treatment methods. These nanoparticle platforms serve not only as inert carriers but also as active participants in the photophysical and biological processes involved in PDT. By improving the physicochemical properties of photosensitizers, optimizing their delivery routes, and enhancing the efficiency of light-to-ROS conversion, nanoparticles form the technological backbone of next-generation PDT.
A major challenge in PDT is the poor solubility and stability of many photosensitizers, such as phthalocyanine and porphyrin derivatives, which are often hydrophobic in nature. This hydrophobicity causes these molecules to aggregate or precipitate in aqueous environments, leading to fluorescence quenching and reduced singlet oxygen production. The aggregation of photosensitizers diminishes their therapeutic efficacy by transferring energy to neighboring molecules as heat instead of generating the ROS required for treatment.
Nanoparticle-based encapsulation technologies offer an effective solution to this issue. By loading hydrophobic photosensitizers into amphiphilic polymer micelles or lipid bilayers, these particles ensure that the photosensitizers remain in a monodispersed, stable state in aqueous environments. For example, nanoparticles made from poly (lactic-co-glycolic acid) (PLGA) provide a biocompatible hydrophobic core that isolates individual photosensitizer molecules, reducing inter-molecular interactions that lead to aggregation. This encapsulation maintains a high quantum yield for singlet oxygen generation and also protects the photosensitizer from degradation due to enzymatic activity or pH changes in biological environments. Furthermore, the encapsulation enhances the stability of the photosensitizers during storage and circulation in the body.
A critical aspect of enhancing PDT efficacy is the precise delivery and accumulation of photosensitizers at the target site, such as tumor tissues, while minimizing systemic side effects. Nanoparticles facilitate the controlled delivery of photosensitizers through both passive and active targeting mechanisms.
Passive Targeting: Tumor tissues often exhibit enhanced permeability and retention (EPR) effects due to their leaky vasculature and impaired lymphatic drainage. Nanoparticles with sizes ranging from 10 to 200 nm can easily penetrate the tumor vasculature and remain trapped in the interstitial spaces of the tumor. The size and surface charge of nanoparticles can be fine-tuned to optimize this passive accumulation process. For instance, nanoparticles with a size of around 50 nm show superior tumor uptake compared to larger particles (e.g., 200 nm), as demonstrated in murine models.
Active Targeting: Active targeting strategies involve functionalizing nanoparticles with ligands that specifically bind to overexpressed receptors on the surface of target cells. Ligands such as folic acid, transferrin, or specific peptides (e.g., RGD) can enhance the specificity of nanoparticle accumulation at tumor sites. The binding of these ligands to their corresponding receptors not only increases local nanoparticle concentration but also promotes receptor-mediated endocytosis, facilitating the efficient internalization of photosensitizers into target cells. The localization of the photosensitizer close to critical cellular organelles, such as mitochondria or lysosomes, further enhances the therapeutic effects of PDT by maximizing the cytotoxic impact of singlet oxygen.
The effectiveness of PDT is often limited by the depth of light penetration in tissues and the efficiency with which photosensitizers generate ROS upon light activation. Nanotechnology offers promising solutions to overcome these physical barriers.
Improving Light Penetration: One major challenge in deep tissue PDT is the limited ability of visible light to penetrate the body. Upconversion nanoparticles (UCNPs) provide a potential solution by converting near-infrared (NIR) light, which has better tissue penetration, into visible light that can activate traditional photosensitizers. UCNPs, composed of rare-earth element-doped crystals, absorb NIR light and, through a series of energy transfer processes, emit higher-energy visible light. This enables the activation of photosensitizers in deeper tissue regions, allowing for more effective treatment of deeper tumors or lesions.
Enhancing ROS Generation: The efficiency of ROS production can be significantly improved by employing energy transfer or catalytic enhancement strategies. One approach involves incorporating fluorescent dyes or molecules within nanoparticles that can transfer absorbed light energy to the photosensitizer through Förster resonance energy transfer (FRET). This boosts the photosensitizer's absorption of specific wavelengths of light, thereby increasing ROS generation. Another strategy involves utilizing nanoparticles with intrinsic catalytic properties, such as those exhibiting peroxidase-like activity, which can decompose hydrogen peroxide (H2O2) into oxygen within the tumor microenvironment. This not only alleviates hypoxic conditions but also sustains ROS production, enabling a continuous and efficient PDT process.
By integrating these strategies, light penetration enhancement, local field amplification, and oxygen self-supply, nanoparticles significantly improve the overall efficacy of PDT, even in deeper tumor sites. In some cases, nanoparticles have been shown to maintain a singlet oxygen quantum yield above 0.5 at depths of up to 1 cm, thereby ensuring that deep-seated lesions can be effectively treated with minimal tissue damage from heat or excessive light exposure.
BOC Sciences offers versatile nanoparticles engineered for targeted drug delivery and therapeutic applications. Our customized solutions enhance treatment efficacy and precision.
Polymeric and lipid-based nanocarriers are widely used in PDT due to their excellent biocompatibility, adjustable drug loading capacities, and minimal toxicity. These nanocarriers are particularly effective for encapsulating and delivering photosensitizers to targeted tissues.
Polymeric Nanocarriers:
Polymeric nanoparticles, such as those made from PLGA, are commonly used for PDT. PLGA nanoparticles, typically in the range of 30–150 nm, offer controlled drug release, allowing for the sustained delivery of photosensitizers over extended periods. The degradation rate of PLGA can be tailored to achieve a consistent release profile, ensuring that the photosensitizer remains active during the treatment window. Additionally, dendritic polymers, with their highly branched structures, can offer precise control over drug loading and surface modification, allowing for targeted delivery and enhanced treatment specificity.
Lipid-Based Nanocarriers:
Lipid-based nanocarriers, particularly liposomes and polymeric micelles, are also popular choices for PDT. Liposomes, which consist of a phospholipid bilayer, are capable of encapsulating both hydrophilic and hydrophobic photosensitizers. Their structure mimics the natural cell membrane, enhancing biocompatibility and stability in biological systems. Furthermore, the surface of liposomes can be modified with targeting ligands to improve tumor localization. Polymeric micelles, formed by amphiphilic block copolymers, have a hydrophobic core that can effectively encapsulate hydrophobic photosensitizers, while their hydrophilic shell stabilizes them in the bloodstream, minimizing premature drug release. These organic carriers are biodegradable and can be metabolized into non-toxic products after completing their therapeutic task.
Inorganic nanoparticles, due to their unique optical, electrical, and catalytic properties, are increasingly integrated into PDT as multifunctional platforms that extend beyond simple drug delivery.
Gold Nanoparticles:
Gold nanoparticles, particularly gold nanorods and gold nanoshells, are widely studied for their plasmonic properties. These particles can efficiently absorb near-infrared light due to surface plasmon resonance, which is particularly useful for PDT since it allows for deeper tissue penetration. Gold nanoparticles not only serve as carriers for photosensitizers but also generate localized heat under light irradiation, enabling simultaneous photothermal therapy. The surface of gold nanoparticles can be easily functionalized with thiol groups, allowing for the attachment of targeting ligands and photosensitizers, enhancing tumor-specific delivery and reducing off-target effects.
Silica Nanoparticles:
Silica nanoparticles, particularly mesoporous silica particles, are valued for their high surface area and tunable pore sizes, which enable efficient encapsulation of photosensitizers. The mesoporous structure of silica allows for the loading of large quantities of photosensitizers, while the silica matrix provides protection from premature degradation. Surface modification strategies, such as the attachment of targeting moieties, can be employed to facilitate active tumor targeting. Additionally, the optical inertness of silica ensures that most of the light energy is directed toward the photosensitizer, improving the efficiency of PDT.
Quantum Dots:
Quantum dots, such as cadmium selenide/zinc sulfide (CdSe/ZnS) or silver sulfide quantum dots, are semiconductor nanocrystals with excellent fluorescence properties. These nanoparticles are capable of wide absorption spectra and narrow emission spectra, making them ideal for use in fluorescence-based PDT. Quantum dots can transfer energy to adjacent photosensitizers through FRET, enhancing the efficiency of PDT. Furthermore, quantum dots are highly stable and their surface can be functionalized to improve biocompatibility and tumor targeting.
Hybrid and stimuli-responsive nanostructures represent an advanced class of nanoparticles that combine the benefits of organic and inorganic materials and incorporate responsive mechanisms that enable more precise control over drug release and therapy.
Hybrid Nanoparticles:
Hybrid nanoparticles integrate both organic and inorganic components to take advantage of the unique properties of each material. For example, gold nanoparticles can serve as the core, providing photothermal capabilities, while mesoporous silica or polymer coatings can be used to load photosensitizers and target specific tissues. This design allows for the combination of photothermal therapy with photodynamic therapy, enhancing the therapeutic effect. The outer surface can be further modified with targeting ligands, enabling the nanoparticles to specifically accumulate in tumor tissues.
Stimuli-Responsive Nanostructures:
Stimuli-responsive nanoparticles are designed to release their payloads in response to specific environmental triggers, such as pH, enzymes, temperature, or light. For example, pH-sensitive nanoparticles can undergo structural changes in response to the acidic microenvironment typical of tumors, leading to the release of photosensitizers at the targeted site. Another example includes temperature-sensitive nanoparticles that release their payload upon exposure to near-infrared light, which induces localized heating, thereby triggering drug release. These smart systems ensure that the photosensitizer is activated only at the tumor site, minimizing damage to healthy tissues and improving the precision of PDT.
Incorporating hybrid and stimuli-responsive elements into nanocarriers enhances their versatility, allowing for more controlled and efficient treatment delivery. These advanced nanostructures not only improve the stability and loading capacity of photosensitizers but also enable their precise activation in response to external stimuli, offering significant improvements in therapeutic outcomes.
With the advancement of nanotechnology, PDT has evolved from a single-modal treatment to a multifunctional and synergistic therapeutic platform. These platforms integrate various therapeutic or diagnostic functions within a single nanostructure, aiming to overcome tumor heterogeneity and complexity, thereby achieving synergistic effects that exceed the sum of individual therapies. This integrated strategy represents a step forward in precision medicine at the nanoscale.
Nanoparticles that combine PDT and photothermal therapy (PTT) are powerful tools for synergistic treatment strategies. PTT utilizes photothermal agents to convert light into heat, generating local hyperthermia to ablate tumor cells. By incorporating both PDT and PTT within a single nanoparticle system, two therapeutic mechanisms can be simultaneously triggered with a single light source.
For example, gold nanocages and copper sulfide nanoparticles, which strongly absorb near-infrared light, serve as efficient photothermal agents while also supporting the generation of ROS through energy transfer from the surface-bound photosensitizer. This dual-action approach not only enhances the therapeutic efficacy by alleviating the hypoxic conditions in tumors but also amplifies ROS production, increasing the susceptibility of tumor cells to oxidative stress. Additionally, localized heating can disrupt tumor cell membranes and inhibit repair proteins, making the cells more sensitive to ROS-induced damage.
The co-delivery of chemotherapeutic drugs and photosensitizers via nanoparticles offers a promising strategy for achieving synchronized, site-specific treatment. Nanoparticles, such as lipid-based carriers, polymeric micelles, or mesoporous silica nanoparticles, are ideal for loading both types of agents due to their versatile structures and high drug-loading capacities.
By carefully controlling the release profile of both agents, this approach ensures that the drugs and photosensitizers reach the tumor site simultaneously, enhancing their therapeutic efficacy. For instance, PLGA-PEG nanoparticles can encapsulate doxorubicin and adsorb Ce6, a photosensitizer. When exposed to light, ROS generated by Ce6 disrupt the lysosomal membrane, facilitating the nuclear translocation of doxorubicin and increasing its cytotoxicity. This synergistic effect allows for a reduction in the required doses of each drug while maintaining or improving treatment efficacy, reducing systemic toxicity.
The tumor microenvironment (TME) exhibits distinct physiological features such as low pH, high levels of hydrogen peroxide, overexpressed enzymes, and hypoxia. These unique characteristics offer opportunities to design intelligent nanoplatforms that can respond to specific stimuli in the TME, enabling precise and on-demand drug release.
Nanoplatforms designed to exploit these features typically use pH-sensitive bonds or redox-sensitive materials that remain stable in the normal physiological conditions but degrade or release their payload under the acidic conditions of the tumor. For example, pH/enzymatic dual-responsive nanogels made from hyaluronic acid and polyhistidine can maintain structural integrity at pH 7.4 but degrade in the acidic TME (pH 6.5), increasing drug penetration and ROS production. This enhanced ROS generation induces immunogenic cell death, which can stimulate the body's immune response against the tumor.
Further, nanoparticles can catalyze the decomposition of excess hydrogen peroxide in the TME to generate oxygen, improving hypoxic conditions and facilitating PDT. Alternatively, nanoparticles that consume intracellular glutathione can enhance the sensitivity of tumor cells to oxidative stress, boosting the efficacy of PDT. These TME-responsive platforms provide highly targeted, efficient, and controlled therapy, significantly improving the precision and outcome of cancer treatment.
One of the key challenges in PDT is the efficient delivery and activation of photosensitizers in deep tissue. BOC Sciences has pioneered the development of intelligent nanocarriers capable of activating the photosensitizers deep within the tissue. Through advanced surface modification techniques, such as the incorporation of targeting molecules and pH-sensitive materials, these nanocarriers can specifically target diseased areas and release their payloads under controlled conditions.
These intelligent carriers are designed to respond to the unique characteristics of the tumor microenvironment, such as low pH, elevated temperature, and increased oxidative stress, thereby enhancing the precision of treatment. For instance, BOC Sciences has synthesized polymer-based, lipid-based, and inorganic nanoparticles that release photosensitizers upon exposure to specific light conditions. This controlled release mechanism significantly enhances the therapeutic potential of PDT, particularly in deep-seated tumors or tissues that are difficult to penetrate.
Moreover, BOC Sciences has incorporated imaging technologies into its nanocarrier platforms, enabling real-time monitoring of treatment progress. This dual-functionality not only allows for precise localization of the therapeutic agents but also ensures maximum therapeutic efficacy.
Table 1. Product Portfolio for Nanoparticle-Enhanced Photodynamic Therapy.
| Product Category | Description | Application | Inquiry |
| Polymeric Nanoparticles | Engineered with tunable particle size, high biocompatibility, and customizable surface chemistry to enhance photosensitizer dispersion and stability. | Photosensitizer loading, sustained-release systems, improving the performance of hydrophobic photosensitizers in PDT workflows. | Inquiry |
| Mesoporous Silica Nanoparticles (MSN) | High surface area and adjustable pore structures enable efficient encapsulation and protection of photosensitizers. | Scenarios requiring high loading capacity, molecular diffusion control, and stability enhancement of photosensitizers. | Inquiry |
| Gold Nanomaterials (Nanorods, Nanoshells, Nanocages) | Offer tunable surface plasmon resonance and strong NIR absorption to support optical enhancement and energy conversion. | Optical amplification strategies, improved energy transfer, and enhanced light–matter interaction in PDT platforms. | Inquiry |
| Quantum Dots | Provide strong photostability and narrow emission peaks, enabling efficient energy transfer to photosensitizers. | FRET-enhanced PDT configurations, fluorescence tracking, and light activation optimization. | Inquiry |
| Stimuli-Responsive Nanomaterials | Designed to undergo structural changes in specific microenvironments, enabling on-demand photosensitizer release. | Precision delivery scenarios that rely on microenvironment-triggered activation to elevate ROS performance. | Inquiry |
| Hybrid Nanomaterials | Integrate multiple functional modules, offering structural stability and adaptable optical properties. | Use cases requiring multi-mechanism enhancement or modular PDT platform engineering. | Inquiry |
BOC Sciences continues to advance photodynamic therapy by developing next-generation nanomaterial platforms that deliver enhanced functionality, controlled release, and improved deep-tissue penetration. With an increasing understanding of nanomaterials, the company has expanded its research beyond traditional photosensitizer carriers, exploring new frontiers such as nanorobots, nanocatalysts, and composite nanomaterials.
A key focus of these advancements is achieving more efficient and targeted treatment outcomes. BOC Sciences has made notable strides in developing new composite materials that enhance the optical activity and biocompatibility of nanocarriers. By utilizing cutting-edge materials such as quantum dots, carbon nanotubes, and metal-organic frameworks (MOFs), the company can modulate light absorption and emission at different wavelengths, thereby broadening the therapeutic scope and improving treatment depth.
In addition, BOC Sciences has explored surface functionalization of nanoparticles, incorporating specific drugs or biomolecules to further enhance the targeting capabilities and therapeutic outcomes. These innovations enable PDT to be applied more effectively to a broader range of diseases, especially in complex, multidimensional research settings.
Table 2. Comprehensive Nanoparticle Services for Advanced PDT Applications.
| Service Category | Service Content | Inquiry |
| Custom Nanoparticle Development | Design and production of polymeric nanoparticles, MSNs, gold nanomaterials, and quantum dots with customizable size, surface engineering, and payload configurations. | Inquiry |
| Photosensitizer Encapsulation & Formulation Optimization | Nanoformulation strategies for hydrophobic or aggregation-prone photosensitizers, improving loading efficiency, stability, and release profiles. | Inquiry |
| Nanostructure Characterization & Quality Analysis | Comprehensive characterization of morphology, particle size, pore structure, and optical performance to support material selection and quality control. | Inquiry |
| Nanoparticle Stability & Compatibility Testing | Evaluation of storage stability, dispersion behavior, and photostability to guide formulation refinement and material screening. | Inquiry |
Through these ongoing innovations, BOC Sciences continues to make substantial contributions to the development of photodynamic nanomaterials. The breakthroughs in intelligent nanocarriers and next-generation PDT platforms set the stage for more effective, precise, and personalized therapeutic approaches in the future.
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