Traditional Photodynamic Therapy Research Articles

Implantable and wireless-controlled antibacterial patch for deep abscess eradication and therapeutic efficacy monitoring

Pyogenic abscesses in deep organs represent severe bacterial infections that can be life-threatening. Traditional photodynamic and sonodynamic hybrid therapy (PDT/SDT) faces various limitations when treating deep organ abscess, including difficulties in drug release control, limited penetration of external laser, a hypoxic microenvironment, and challenges in therapeutic efficacy monitoring. To address these issues, we developed an implantable and wireless-controlled antibacterial patch integrated with modules for on-demand drug release, light control and therapeutic efficacy monitoring, providing a comprehensive solution to the clinical challenges of PDT/SDT in treating deep organ abscess. This self-adhesive and miniaturized patch can easily attach to internal tissues, and be wirelessly powered and controlled by external ultrasound. Initially, ultrasound powered the patch’s drug release module through the lead zirconate titanate piezoelectric transducer (PZT), providing distinct electrical-thermal release signals for indocyanine green (ICG) and hemoglobin (Hb). This ensured that Hb was released first to generate oxygen, alleviating the hypoxic microenvironment at the infection site, followed by the release of ICG as both a photosensitizer and sonosensitizer. Subsequently, ultrasound directly activated the sonosensitizer and powered the µLEDs in the light control module, ultimately initiating SDT/PDT hybrid antibacterial treatment. The therapeutic efficacy monitoring module in the patch used hydrogels with infection detection capabilities to provide timely feedback on the treatment status of the infected lesions, enabling doctors to rapidly adjust treatment plans and significantly improve the flexibility and effectiveness of treatments. Both in vitro and in vivo experiments have demonstrated that the patch can completely cure pyogenic liver abscesses. This research also exhibits promise for extending the application of the patch to treat other types of deep infections.

Molecular Engineering of Pure Superoxide Radical Photogenerator for Hypoxia-Tolerant Tumor Theranostics.

Photodynamic therapy (PDT) is a promising cancer treatment, but limited oxygen supply in tumors (hypoxia) can hinder its effectiveness. This is because traditional PDT relies on Type-II reactions that require oxygen. Type-I photosensitizers (PSs) offer a promising approach to overcome the limitations of tumor photodynamic therapy (PDT) in hypoxic environments. To leverage the advantages of Type-I PDT, the design and evaluation of a series of Type-I PSs for developing pure Type-1 PSs, by incorporating benzene, thiophene, or bithiophene into the donor-acceptor molecular skeleton are reported. Among them, CTTI (with bithiophene) shows the best performance, generating the most superoxide radical (O2 •-) upon light irradiation. Importantly, CTTI exclusively produced superoxide radicals, avoiding the less effective Type-II pathway. This efficiency is due to CTTI's energy gap and low reduction potential, which favor electron transfer to oxygen for O2 •- generation. Finally, CTTI NPs are successfully fabricated by encapsulating CTTI into liposomes, and validated to be effective in killing tumor cells, even under hypoxic conditions, making them promising hypoxia-tolerant tumor phototheranostic agents in both in vitro and in vivo applications.

A Novel Boron Dipyrromethene-Erlotinib Conjugate for Precise Photodynamic Therapy against Liver Cancer.

Photodynamic Therapy (PDT) is recognized for its exceptional effectiveness as a promising cancer treatment method. However, it is noted that overexposure to the dosage and sunlight in traditional PDT can result in damage to healthy tissues, due to the low tumor selectivity of currently available photosensitizers (PSs). To address this challenge, we introduce herein a new strategy where the small molecule-targeted agent, erlotinib, is integrated into a boron dipyrromethene (BODIPY)-based PS to form conjugate 6 to enhance the precision of PDT. This conjugate demonstrates optical absorption, fluorescence emission, and singlet oxygen generation efficiency comparable to the reference compound 7, which lacks erlotinib. In vitro studies reveal that, after internalization, conjugate 6 predominantly accumulates in the lysosomes of HepG2 cells, exhibiting significant photocytotoxicity with an IC50 value of 3.01 µM. A distinct preference for HepG2 cells over HELF cells is observed with conjugate 6 but not with compound 7. In vivo experiments further confirm that conjugate 6 has a specific affinity for tumor tissues, and the combination treatment of conjugate 6 with laser illumination can effectively eradicate H22 tumors in mice with outstanding biosafety. This study presents a novel and potential PS for achieving precise PDT against cancer.

Dissecting Exciton Dynamics in pH‐Activatable Long‐Wavelength Photosensitizers for Traceable Photodynamic Therapy

Tumor‐specific activatable long‐wavelength (LW) photosensitizers (PSs) show promise in overcoming the limitations of traditional photodynamic therapy (PDT), such as systemic phototoxicity and shallow tissue penetration. However, their insufficient LW light absorption and low singlet oxygen quantum yield (F1O2) usually require high laser power density to produce thermal energy and synergistically enhance PDT. The strong photothermal radiation causing acute pain significantly reduces patient compliance and hinders the broader clinical application of LW PDT. Through the exciton dynamics dissection strategy, we have developed a series of pH‐activatable cyanine‐based LW PSs (LET‐R, R = H, Cl, Br, I), among which the activated LET‐I exhibits strong light absorption at 808 nm and a remarkable 3.2‐fold enhancement in F1O2 compared to indocyanine green. Transient spectroscopic analysis and theoretical calculations confirmed its significantly promoted intersystem crossing and simultaneously enhanced LW fluorescence emission characteristics. These features enable the activatable fluorescence and photoacoustic dual‐modal imaging‐escorted complete photodynamic eradication of tumors by the folic acid (FA)‐modified LET‐I probe (LET‐I‐FA), under the ultralow 808 nm laser power density (0.2 W cm‐2) for irradiation, without the need for photothermal energy synergy. This research presents a novel strategy of dissecting exciton dynamics to screen activatable LW PSs for traceable PDT.

Dissecting Exciton Dynamics in pH-Activatable Long-Wavelength Photosensitizers for Traceable Photodynamic Therapy.

Tumor-specific activatable long-wavelength (LW) photosensitizers (PSs) show promise in overcoming the limitations of traditional photodynamic therapy (PDT), such as systemic phototoxicity and shallow tissue penetration. However, their insufficient LW light absorption and low singlet oxygen quantum yield (Φ 1O2) usually require high laser power density to produce thermal energy and synergistically enhance PDT. The strong photothermal radiation causing acute pain significantly reduces patient compliance and hinders the broader clinical application of LW PDT. Through the exciton dynamics dissection strategy, we have developed a series of pH-activatable cyanine-based LW PSs (LET-R, R = H, Cl, Br, I), among which the activated LET-I exhibits strong light absorption at 808 nm and a remarkable 3.2-fold enhancement in Φ 1O2 compared to indocyanine green. Transient spectroscopic analysis and theoretical calculations confirmed its significantly promoted intersystem crossing and simultaneously enhanced LW fluorescence emission characteristics. These features enable the activatable fluorescence and photoacoustic dual-modal imaging-escorted complete photodynamic eradication of tumors by the folic acid (FA)-modified LET-I probe (LET-I-FA), under the ultralow 808 nm laser power density (0.2 W cm-2) for irradiation, without the need for photothermal energy synergy. This research presents a novel strategy of dissecting exciton dynamics to screen activatable LW PSs for traceable PDT.

Low-Cytotoxic Core-Sheath ZnO NWs@TiO2-xNy Triggered Piezo-photocatalytic Antibacterial Activity.

Sonophotodynamic antimicrobial therapy (SPDAT) is recognized as a highly efficient biomedical treatment option, known for its versatility and remarkable healing outcomes. Nevertheless, there is a scarcity of sonophotosensitizers that demonstrate both low cytotoxicity and exceptional antibacterial effectiveness in clinical applications. In this paper, a novel ZnO nanowires (NWs)@TiO2-xNy core-sheath composite was developed, which integrates the piezoelectric effect and heterojunction to build dual built-in electric fields. Remarkably, it showed superb antibacterial effectiveness (achieving 95% within 60 min against S. aureus and ∼100% within 40 min against E. coli, respectively) when exposed to visible light and ultrasound. Due to the continuous interference caused by light and ultrasound, the material's electrostatic equilibrium gets disrupted. The modification in electrical properties facilitates the composite's ability to attract bacterial cells through electrostatic forces. Moreover, Zn-O-Ti and Zn-N-Ti bonds formed at the interface of ZnO NWs@TiO2-xNy, further enhancing the dual internal electric fields to accelerate the excited carrier separation to generate more reactive oxygen species (ROS), and thereby boosting the antimicrobial performance. In addition, the TiO2 layer limited Zn2+ dissolution into solution, leading to good biocompatibility and low cytotoxicity. Lastly, we suggest a mechanistic model to offer practical direction for the future development of antibacterial agents that are both low in toxicity and high in efficacy. In comparison to the traditional photodynamic therapy systems, ZnO NWs@TiO2-xNy composites exhibit super piezo-photocatalytic antibacterial activity with low toxicity, which shows great potential for clinical application as an antibacterial nanomaterial.

The fusion of light and immunity: Advancements in photoimmunotherapy for melanoma.

Metastatic melanoma is an aggressive skin cancer with high mortality and recurrence rates. Despite the clinical success of recent immunotherapy approaches, prevailing resistance rates necessitate the continued development of novel therapeutic options. Photoimmunotherapy (PIT) is emerging as a promising immunotherapy strategy that uses photodynamic therapy (PDT) to unleash systemic immune responses against tumor sites while maintaining the superior tumor-specificity and minimally invasive nature of traditional PDT. In this review, we discuss recent advances in PIT and strategies for the management of melanoma using PIT. PIT can strongly induce immunogenic cell death, inviting the concomitant application of immune checkpoint blockade or adoptive cell therapies. PIT can also be leveraged to selectively remove the suppressive immune populations associated with immunotherapy resistance. The modular nature of PIT therapy design combined with the potential for patient-specific antigen selection or drug co-delivery makes PIT an alluring option for future personalized melanoma care.

A tumor-targeted multifunctional nanosystem with light-triggered NO generation for synergistic photodynamic/gas therapy

Photodynamic therapy (PDT) has emerged as a promising strategy for cancer treatment. Nevertheless, PDT alone still faces a considerable challenge in efficiently eliminating cancer cells, and combination with other therapeutic strategies can significantly improve anticancer efficacy. Herein, a multifunctional nanosystem (Ru-PArg-HA) composed of biocompatible and tumor-targeted hyaluronic acid (HA), a photosensitizer [Ru(phen)2(PIP-OCH3)]2+ (termed Ru, phen = 1,10-phenanthroline, PIP-OCH3 = 2-(4-methoxy phenyl)-1H-imidazo[4,5-f] [1,10] phenanthroline) and a NO donor poly-l-arginine (PArg), was fabricated via electrostatic interactions. Under 470 nm light irradiation, Ru-PArg-HA could not only catalyze 1,4-dihydronicotinamide adenine dinucleotide (NADH) oxidation to produce H2O2, but also could generate a large amount of reactive oxygen species (ROS, including 1O2 and O2−) for PDT therapy. The light-driven production of 1O2 and H2O2 could further convert PArg into nitric oxide (NO), enabling synergistic gas therapy. The experimental outcomes demonstrated that Ru-PArg-HA exhibited much enhanced anticancer activity compared to traditional mono-modal PDT. This finding provides new inspiration for the development of multifunctional nanosystems with efficient and targeted anticancer activity.

A piezoelectric-driven microneedle platform for skin disease therapy

With over a million cases detected each year, skin disease is a global public health problem that diminishes the quality of life due to its difficulty to eradicate, propensity for recurrence, and potential for post-treatment scarring. Photodynamic therapy (PDT) is a treatment with minimal invasiveness or scarring and few side effects, making it well tolerated by patients. However, this treatment requires further research and development to improve its effective clinical use. Here, a piezoelectric-driven microneedle (PDMN) platform that achieves high efficiency, safety, and non-invasiveness for enhanced PDT is proposed. This platform induces deep tissue cavitation, increasing the level of protoporphyrin IX and significantly enhancing drug penetration. A clinical trial involving 25 patients with skin disease was conducted to investigate the timeliness and efficacy of PDMN-assisted PDT (PDMN-PDT). Our findings suggested that PDMN-PDT boosted treatment effectiveness and reduced the required incubation time and drug concentration by 25% and 50%, respectively, without any anesthesia compared to traditional PDT. These findings suggest that PDMN-PDT is a safe and minimally invasive approach for skin disease treatment, which may improve the therapeutic efficacy of topical medications and enable translation for future clinical applications.

Deciphering Oxygen-Independent Augmented Photodynamic Oncotherapy by Facilitating the Separation of Electron-Hole Pairs.

Developing Type-I photosensitizers provides an attractive approach to solve the dilemma of inadequate efficacy of photodynamic therapy (PDT) caused by the inherent oxygen consumption of traditional Type-II PDT and anoxic tumor microenvironment. The challenge for the exploration of Type-I PSs is to facilitate the electron transfer ability of photosensitization molecules for transforming oxygen or H2O to reactive oxygen species (ROS). Herein, we propose an electronic acceptor-triggered photoinduced electron transfer (a-PET) strategy promoting the separation of electron-hole pairs by marriage of two organic semiconducting molecules of a non-fullerene scaffold-based photosensitizer and a perylene diimide that significantly boost the Type-I PDT pathway to produce plentiful ROS, especially, inducing 3.5-fold and 2.5-fold amplification of hydroxyl (OH⋅) and superoxide (O2 -⋅) generation. Systematic mechanism exploration reveals that intermolecular electron transfer and intramolecular charge separation after photoirradiation generate a competent production of radical ion pairs that promote the Type-I PDT process by theoretical calculation and ultrafast femtosecond transient absorption (fs-TA) spectroscopy. By complementary tumor diagnosis with photoacoustic imaging and second near-infrared fluorescence imaging, this as-prepared nanoplatform exhibits fabulous photocytotoxicity in harsh hypoxic conditions and terrific cancer revoked abilities in living mice. We envision that this work will broaden the insight into high-efficiency Type-I PDT for cancer phototheranostics.

Precise Photodynamic Therapy by Midkine Nanobody-Engineered Nanoparticles Remodels the Microenvironment of Pancreatic Ductal Adenocarcinoma and Potentiates the Immunotherapy.

Pancreatic ductal adenocarcinoma (PDAC) is notorious for its resistance against chemotherapy and immunotherapy due to its dense desmoplastic and immunosuppressive tumor microenvironment (TME). Traditional photodynamic therapy (PDT) was also less effective for PDAC owing to poor selectivity, insufficient penetration, and accumulation of photosensitizers in tumor sites. Here, we designed a light-responsive novel nanoplatform targeting the TME of PDAC through tumor-specific midkine nanobodies (Nbs), which could efficiently deliver semiconducting polymeric nanoparticles (NPs) to the TME of PDAC and locally produce abundant reactive oxygen species (ROS) for precise photoimmunotherapy. The synthesized nanocomposite can not only achieve multimodal imaging of PDAC tumors (fluorescence and photoacoustic imaging) but also lead to apoptosis and immunogenic cell death of tumor cells via ROS under light excitation, ultimately preventing tumor progression and remodeling the immunosuppressive TME with increased infiltration of T lymphocytes. Combined with a PD-1 checkpoint blockade, the targeted PDT platform showed the best antitumor performance and markedly extended mice survival. Conclusively, this work integrating Nbs with photodynamic NPs provides a novel strategy to target formidable PDAC to achieve tumor suppression and activate antitumor immunity, creating possibilities for boosting efficacy of immunotherapy for PDAC tumors through the combination with precise local PDT.

Achieving precise non-invasive ROS spatiotemporal manipulation for colon cancer immunotherapy

Colon cancer (CC) stands as a formidable global health challenge, ranking as the third leading cause of cancer-related mortality. Traditional photodynamic therapy encounters limitations stemming from the limited penetration depth of light and the effective regulation of reactive oxygen species (ROS). Here, we present an in-situ ROS spatiotemporal manipulation system that synergizes the power of piezoelectric nanoparticles with potent immune adjuvants. This exclusive ROS nanogenerator exhibits precision in targeting colon tumor sites, inducing controlled oxidative stress to eliminate malignant cells, while simultaneously unleashing the full potential of the immune system to suppress cancer cell growth and impede metastasis. Notably, this system achieves spatiotemporal manipulation of ROS through piezocatalytic mechanisms triggered self-generated ROS. Moreover, it skillfully customizes ROS production in response to tumor size, optimizing therapeutic efficacy with precision. To enhance the therapeutic efficacy, glucan, a bioactive polysaccharide that augments the immune response while simultaneously inhibiting the spread of cancer cells, is integrated. This cancer treatment approach is enabling precise ROS generation and immune modulation at the tumor site, ushering in a new era of dynamic immunotherapy.

A self-enhanced chemiexcited PDT system for targeted and efficient treatment of deeply seated tumors

NP3 with H2O2 supplementation and self-enhanced chemiexcited PDT system are developed, exhibiting efficient chemiexcited PDT activity towards subcutaneously implanted and lung metastatic tumors, providing new insights for development of novel chemiexcited PDT.

Low-dose X-ray stimulated NO-releasing nanocomposites for closed-loop dual-mode cancer therapy.

X-ray-excited photodynamic therapy (X-PDT) employs X-rays as an energy source, overcoming the light penetration limitations of traditional photodynamic therapy (PDT) but is constrained by high-energy radiation and the hypoxic tumor microenvironment. Low-dose X-ray-excited photodynamic therapy and reduction of mitochondrial oxygen consumption can serve as significant breakthroughs in overcoming these barriers. In this study, NaLuF4:Tb/Gd (15%/5%)@NaYF4 (ScNP) nanoparticles adsorbing the photosensitizer MC540 and loaded with α-(nitrate ester) acid (NEAA) were prepared as low X-ray dose triggered nano-scintillators. The final product obtained was NaLuF4:Tb/Gd (15%/5%)@NaYF4@mSiO2@MC540@NEAA (ScNP-MS@MC540@NEAA) nanocomposites, which exhibited intense green luminescence. X-PDT generates cytotoxic reactive oxygen species (ROS) with minimal ionizing radiation damage. Simultaneously, NEAA reacts with glutathione (GSH) to generate nitric oxide (NO) for gaseous treatment of the damaged mitochondrial respiratory chain to reduce oxygen consumption and alleviate hypoxia, enhancing the X-PDT efficacy and realizing a closed-loop treatment. The superoxide ions (˙O2-) can rapidly react with NO produced to form the highly cytotoxic reactive nitrogen species (RNS) peroxynitrite anion (ONOO-), which exhibits higher cytotoxicity compared to ROS. Furthermore, GSH scavenges toxic ROS and maintains the physiological function of tumor cells. It can induce cancer cell overoxidation and nitrosative stress. This work describes a low-dose X-ray-triggered X-PDT system with total radiation of 50 mGy, which involves GSH consumption, self-supplied NO, mitochondrial damage alleviation, and hypoxia relief to generate ROS and RNS, forming a closed-loop anti-hypoxia dual-mode system with synergistically enhanced anti-tumor effects, without significant biological side effects. It provides a promising platform for deep-seated tumor X-PDT with considerable application prospects.

A Targeting Singlet Oxygen Battery for Multidrug-Resistant Bacterial Deep-Tissue Infections.

Traditional photodynamic therapy (PDT) is dependent on externally applied light and oxygen, and the depth of penetration of these factors can be insufficient for the treatment of deep infections. The short half-life and short diffusion distance of reactive oxygen species (ROS) also limit the antibacterial efficiency of PDT. Herein, we designed a targeting singlet oxygen delivery system, CARG-Py, for irradiation-free and oxygen-free PDT. This system was converted to the "singlet oxygen battery" CARG-1 O2 and released singlet oxygen without external irradiation or oxygen. CARG-1 O2 is composed of pyridones coupled to a targeting peptide that improves the utilization of singlet oxygen in deep multidrug-resistant bacterial infections. CARG-1 O2 was shown to damage DNA, protein, and membranes by increasing the level of reactive oxygen inside bacteria; the attacking of multiple biomolecular sites caused the death of methicillin-resistant Staphylococcus aureus (MRSA). An in vivo study in a MRSA-infected mouse model of pneumonia demonstrated the potential of CARG-1 O2 for the efficient treatment of deep infections. This work provides a new strategy to improve traditional PDT for irradiation- and oxygen-free treatment of deep infections while improving convenience of PDT.

A Targeting Singlet Oxygen Battery for Multidrug‐Resistant Bacterial Deep‐Tissue Infections

AbstractTraditional photodynamic therapy (PDT) is dependent on externally applied light and oxygen, and the depth of penetration of these factors can be insufficient for the treatment of deep infections. The short half‐life and short diffusion distance of reactive oxygen species (ROS) also limit the antibacterial efficiency of PDT. Herein, we designed a targeting singlet oxygen delivery system, CARG‐Py, for irradiation‐free and oxygen‐free PDT. This system was converted to the “singlet oxygen battery” CARG‐1O2 and released singlet oxygen without external irradiation or oxygen. CARG‐1O2 is composed of pyridones coupled to a targeting peptide that improves the utilization of singlet oxygen in deep multidrug‐resistant bacterial infections. CARG‐1O2 was shown to damage DNA, protein, and membranes by increasing the level of reactive oxygen inside bacteria; the attacking of multiple biomolecular sites caused the death of methicillin‐resistant Staphylococcus aureus (MRSA). An in vivo study in a MRSA‐infected mouse model of pneumonia demonstrated the potential of CARG‐1O2 for the efficient treatment of deep infections. This work provides a new strategy to improve traditional PDT for irradiation‐ and oxygen‐free treatment of deep infections while improving convenience of PDT.

Internal Light Sources-Mediated Photodynamic Therapy Nanoplatforms: Hope for the Resolution of the Traditional Penetration Problem.

Photodynamic therapy (PDT) is an alternative cancer treatment technique with a noninvasive nature, high selectivity, and minimal adverse effects. The indispensable light source used in PDT is a critical factor in determining the energy conversion of photosensitizers (PSs). Traditional light sources are primarily concentrated in the visible light region, severely limiting their penetration depth and making them prone to scattering and absorption when applied to biological tissues. For that reason, its efficacy in treating deep-seated lesions is often inadequate. Self-exciting PDT, also known as auto-PDT (APDT), is an attractive option for circumventing the limited penetration depth of traditional PDT and has acquired significant attention. APDT employs depth-independent internal light sources to excite PSs through resonance or radiative energy transfer. APDT has considerable potential for treating deep-tissue malignancies. To facilitate many researchers' comprehension of the latest research progress in this field and inspire the emergence of more novel research results. This review introduces internal light generation mechanisms and characteristics and provides an overview of current research progress based on the recently reported APDT nanoplatforms. The current challenges and possible solutions of APDT nanoplatforms are also presented and provide insights for future research in the final section of this article.

NIR-II Light-Activated Gold Nanorods for Synergistic Thermodynamic and Photothermal Therapy of Tumor.

There are tricky challenges in tumor therapy due to the hypoxic tumor microenvironment, inevitably inhibiting the treatment efficacy of the traditional photodynamic therapy (PDT), radiation therapy (RT), and sonodynamic therapy (SDT). Herein, to overcome tumor hypoxia limitation, we constructed a near-infrared II (NIR-II) light-triggered thermodynamic therapy (TDT) nanoplatform of Au@mSiO2-AIPH@PCM/PEG (ASAPP) by integrating the Au nanorods (Au NRs) and thermally activated alkyl free radical-releasing molecules (AIPH). Au NRs@mSiO2 was used as a photothermally responsive material and AIPH carrier, and the hot-melt phase-change material (PCM) was used as a capping agent to prevent leakage of AIPH during blood circulation. Upon NIR-II light irradiation, heat-triggered free radical release from AIPH was successfully achieved for killing cancer cells in vitro and in vivo without oxygen dependence, leading to synergistically enhanced antitumor therapy.

A multi-stimuli responsive alginate nanogel for anticancer chemo-photodynamic therapy

Stimuli-responsive nanosystems enable highly effective targeting and therapeutic functions, including chemotherapy and photodynamic therapy (PDT). Traditional PDT alone cannot effectively eradicate the tumor burden; combined with chemotherapy, this combination presents a powerful treatment modality to modulate the tumor microenvironment (TME). Herein, we report a multi-stimulus responsive alginate nanogel that responds to the change in pH and redox potential in the TME. We coupled oxidized alginate with 4-mercapto phenylboronic acid and pheophorbide-A (a hydrophobic photosensitizer) and conjugated with adipic acid dihydrazide to design the nanogels. Further, we encapsulated doxorubicin, a cytotoxic agent, in the nanogel to enable chemotherapy. The alginate nanogel exhibited the pH-sensitive release of both pheophorbide-Aand doxorubicin and simultaneously reduced the redox potential that enhanced PDT by increasing reactive oxygen species production. Our results demonstrate that the multi-stimuli responsive alginate nanogel enhances toxicity in breast cancer and melanoma.

Pharmacological Agents Used in the Prevention and Treatment of Actinic Keratosis: A Review

Actinic keratosis (AK) is among the most commonly diagnosed skin diseases with potentially life-threatening repercussions if left untreated. Usage of pharmacologic agents represents one of many therapeutic strategies that can be used to help manage these lesions. Ongoing research into these compounds continues to change our clinical understanding as to which agents most benefit particular patient populations. Indeed, factors such as past personal medical history, lesion location and tolerability of therapy only represent a few considerations that clinicians must account for when prescribing appropriate treatment. This review focuses on specific drugs used in either the prevention or treatment of AKs. Nicotinamide, acitretin and topical 5-fluorouracil (5-FU) continue to be used with fidelity in the chemoprevention of actinic keratosis, although some uncertainty persists in regard to which agents should be used in immunocompetent vs. immunodeficient/immunosuppressed patients. Topical 5-FU, including combination formulations with either calcipotriol or salicylic acid, as well as imiquimod, diclofenac and photodynamic light therapy are all accepted treatment strategies employed to target and eliminate AKs. Five percent of 5-FU is regarded as the most effective therapy in the condition, although the literature has conflictingly shown that lower concentrations of the drug might also be as effective. Topical diclofenac (3%) appears to be less efficacious than 5% 5-FU, 3.75-5% imiquimod and photodynamic light therapy despite its favorable side effect profile. Finally, traditional photodynamic light therapy, while painful, appears to be of higher efficacy in comparison to its more tolerable counterpart, daylight phototherapy.