Hypericin-Mediated Photodynamic Therapy for Head and Neck Cancers: A Systematic Review
Abstract
:1. Introduction
1.1. Rationale
1.2. Objectives
2. Materials and Methods
2.1. Focused Question and Null Hypothesis
2.2. Search Strategy
2.3. Selection of Studies
2.4. Risk of Bias in Individual Studies
2.5. Quality Assessment
- Was the specific concentration of hypericin as the photosensitizer clearly indicated?
- Was the origin or source of the hypericin provided?
- Was the incubation time for the hypericin clearly stated?
- Were detailed light source parameters (type, wavelength, energy density, fluence, and power density) reported?
- Was a power meter used to verify the light parameters?
- Was a negative control group included in the experimental design?
- Were numerical results reported with relevant statistical analyses?
- Was there a clear method for addressing missing outcome data?
- Was the study free from potential conflicts of interest related to its source of funding?
2.6. Risk of Bias Across Studies and Quality Assessment Presentation
2.7. Data Extraction
3. Results
3.1. Study Selection
3.2. General Characteristics of the Included Studies
3.3. Main Study Outcomes
3.4. Characteristics of Light Sources Used in PDT
4. Discussion
4.1. Results in the Context of Other Evidence
4.2. Limitations of the Evidence
4.3. Limitations of the Review Process
4.4. Implications for Practice, Policy, and Future Research
5. Conclusions
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Source | Search Term | Number of Results |
---|---|---|
PubMed/MEDLINE | ((“Hypericin”) AND (“Photodynamic Therapy” OR “Photochemotherapy”) AND (“Squamous Cell Carcinoma” OR “Oral Cancer” OR “Carcinoma”) AND (“Keratinocytes” OR “Fibroblasts” OR “Cells”)) | 81 |
Embase | (‘hypericin’/exp OR ‘hypericin’) AND (‘photodynamic therapy’/exp OR ‘photodynamic therapy’ OR ‘photochemotherapy’/exp OR ‘photochemotherapy’) AND (‘squamous cell carcinoma’/exp OR ‘squamous cell carcinoma’ OR ‘oral cancer’/exp OR ‘oral cancer’ OR ‘carcinoma’/exp OR ‘carcinoma’) AND (‘keratinocyte’/exp OR ‘keratinocyte’ OR ‘fibroblast’/exp OR ‘fibroblast’ OR ‘cell’/exp OR ‘cell’) | 180 |
Scopus | (TITLE-ABS-KEY(hypericin) AND (TITLE-ABS-KEY(“photodynamic therapy”) OR TITLE-ABS-KEY(photochemotherapy)) AND (TITLE-ABS-KEY(“squamous cell carcinoma”) OR TITLE-ABS-KEY(“oral cancer”) OR TITLE-ABS-KEY(carcinoma)) AND (TITLE-ABS-KEY(keratinocyte) OR TITLE-ABS-KEY(fibroblast) OR TITLE-ABS-KEY(cell)) | 168 |
Cochrane | (MH “Hypericin” OR “Hypericin”) AND (“Photodynamic Therapy” OR “Photochemotherapy” OR “Light Therapy”) AND (“Carcinoma” OR “Squamous Cell Carcinoma” OR “Cancer” OR “Oral Cancer” OR “Neoplasms”) | 5 |
Inclusion Criteria | Exclusion Criteria |
---|---|
Preclinical studies (e.g., in vitro, in vivo models). Clinical studies (e.g., randomized controlled trials, cohort studies). Review articles and meta-analyses relevant to PDT with hypericin or riboflavin. Studies addressing squamous cell carcinoma, including subtypes (oral squamous cell carcinoma, head and neck squamous cell carcinoma). Use of hypericin or riboflavin in photodynamic therapy. Cellular and molecular effects (e.g., apoptosis, necrosis, oxidative stress). Tumor response (e.g., reduction in tumor size, viability). Immunomodulatory effects. Articles published in English or Polish. Studies published within the last 25 years. | Gray literature Studies unrelated to PDT or those using different photosensitizers than hypericin or riboflavin. Non-original research, such as editorials or opinions without data. Studies focused on other cancer types, without relevance to the head and neck region. Animal or cell-line studies that do not include squamous cell carcinoma models. Lack of specific results on PDT efficacy or mechanisms. Articles with incomplete data, inaccessible full texts, or unpublished studies. Articles published in languages other than English or Polish, unless a translation is available. |
Study | Question | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | Total | Classification | |
Bhuvaneswari et al. (2007) [26] | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 0 | 0 | 6 | Moderate |
Blank et al. (2001) [27] | 1 | 0 | 0 | 1 | 0 | 1 | 1 | 0 | 1 | 5 | Moderate |
Bublik et al. (2006) [28] | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 8 | Low |
Du et al. (2002) [29] | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 8 | Low |
Du et al. (2003) [30] | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 8 | Low |
Du et al. (2004) [31] | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 8 | Low |
Head et al. (2006) [32] | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 0 | 1 | 7 | Low |
Olek et al. (2023) [23] | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 9 | Low |
Olek et al. (2024) [24] | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 9 | Low |
Sharma et al. (2012) [33] | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 0 | 1 | 6 | Moderate |
Laffers et al. (2015) [34] | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 0 | 0 | 6 | Moderate |
Wozniak et al. (2023) [35] | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 0 | 1 | 7 | Low |
Xu et al. (2010) [25] | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 9 | Low |
Author and Year | Country | Study Design |
---|---|---|
Bhuvaneswari et al. (2007) [26] | Singapore | In vivo study |
Blank et al. (2001) [27] | Israel | In vivo study |
Bublik et al. (2006) [28] | USA | In vitro study |
Du et al. (2002) [29] | Singapore | In vitro study |
Du et al. (2003) [30] | Singapore | In vivo study |
Du et al. (2004) [31] | Singapore | In vitro study |
Head et al. (2006) [32] | USA | In vitro study |
Olek et al. (2023) [23] | Poland | In vitro study |
Olek et al. (2024) [24] | Poland | In vitro study |
Sharma et al. (2012) [33] | South Africa | In vitro study |
Laffers et al. (2015) [34] | Germany | In vitro study |
Wozniak et al. (2023) [35] | Poland | In vitro study |
Xu et al. (2010) [25] | China | In vitro study |
Study Authors | Cancer Cell Type | Focus | Mechanisms Explored | Outcomes | Treatment Related Adverse Events |
---|---|---|---|---|---|
Bhuvaneswari et al. (2007) [26] | HK1, CNE-2 | VEGF expression post-PDT | Photodynamic therapy induces hypoxia within tumors, which triggers the expression of VEGF through the HIF-1α pathway. The use of celebrex (a COX-2 inhibitor) to modulate VEGF expression post-PDT. | VEGF levels are initially downregulated post-PDT but are upregulated within 72 h, indicating tumor regrowth. Combination therapy with celebrex significantly downregulates VEGF expression, potentially improving PDT outcomes. | |
Blank et al. (2001) [27] | Highly invasive solid tumors; DA3Hi mammary adenocarcinoma and SQ2 squamous cell carcinoma. | Evaluating the tumoricidal effects of HY-PDT on primary tumor development, survival rates, and metastatic spread in mice. | HY-PDT induces extensive tumor necrosis and inflammation but not significant immune antitumoral responses. The therapy stimulates the expression of inflammatory cytokines (e.g., IL-1β, IL-6, TNF-α) in tumor tissues and systemically in the spleen. No significant effect on immune-related cytokine mRNAs, such as IL-2, IL-4, and IFN-γ, was observed. | HY-PDT delayed tumor development and prolonged survival in mice when applied to smaller tumors. It was more effective on SQ2 squamous cell carcinoma compared with DA3Hi adenocarcinoma. Slight reductions in metastatic burden were observed in SQ2-bearing mice, but no significant effects were noted in DA3Hi-bearing mice. HY-PDT induced extensive tumor necrosis, accompanied by local and systemic inflammatory responses, as evidenced by elevated mRNA levels of inflammation-related cytokines (e.g., IL-1β, IL-6, TNF-α). However, no antitumoral immune responses were observed. | Limited systemic immune responses and an absence of HY-PDT-induced antitumoral immunity. Potential for localized tissue damage and inflammatory reactions at treatment sites. |
Bublik et al. (2006) [28] | HNSCC | Evaluating HY-PDT using pulsed laser light at various wavelengths to determine optimal conditions for phototoxicity and tumor targeting in vitro. | Hypericin is activated by laser light to generate singlet oxygen and reactive species, leading to tumor cell death. Light absorption peaks at 545 and 595 nm, with 593 nm being the optimal wavelength for phototoxicity. Picosecond pulsed laser light is more effective than millisecond pulses due to higher intensity and deeper tissue penetration. Hypericin localizes predominantly in the perinuclear region, affecting the endoplasmic reticulum and Golgi apparatus. | Hypericin absorbs light at 545 and 595 nm and emits fluorescence at 594 and 640 nm, with its tricyclic structure enabling the production of singlet oxygen, which is crucial for PDT. In vitro studies on SCC show that phototoxicity increases with hypericin concentration, exposure time, and laser power, with a significant linear increase in cell toxicity observed at higher drug doses and light fluence. Phototoxicity was enhanced at wavelengths near hypericin’s absorption peaks, with 550 nm light showing similar effectiveness to 514 nm light but requiring less energy. The optimal wavelength for PDT was found to be 593 nm, where minimal energy was required for maximum tumor toxicity. Picosecond laser pulses induced greater tumor cell cytotoxicity compared with millisecond pulses, even with equal energy delivery, suggesting that the higher intensity of shorter pulses is more effective. Confocal microscopy revealed that hypericin accumulates in the perinuclear region of SCC cells, leading to rapid cytotoxic effects, such as cell blebbing, upon light exposure, confirming its potential for inducing fluorescence and tumor phototoxicity under both visible and infrared light activation. | Limited systemic toxicity observed, but specific adverse events were not detailed as this was an in vitro study. |
Du et al. (2002) [29] | NPC/HK1 | Investigating the endogenous production of cytokines (IL-8 and IL-10) in two EBV-positive NPC cell lines (HK1 and CNE-2) and assessing the effects of hypericin and hypericin-mediated photodynamic therapy on these cytokines. | PDT is known to upregulate IL-8 transcription via ROS and activate the IL-10 promoter. | IL-8 was constitutively expressed in both cell lines; levels were 2-fold higher in HK1 compared with CNE-2 (p = 0.0004). Hypericin increased IL-8 by almost 30% in HK1 cells (p = 0.0180). IL-10 was undetectable in all conditions. HY-PDT did not significantly alter IL-8 or IL-10 levels in either cell line. Cytokine responses varied between cell lines, highlighting tumor microenvironment differences. | No specific adverse effects linked to cytokine production were reported. |
Du et al. (2003) [30] | NPC/HK1 | Evaluation of the efficacy of HY-PDT for treating NPC, emphasizing the relationship between hypericin biodistribution and photodynamic effects. | Biodistribution of hypericin: Rapid plasma peak concentration at 1 h post-administration, with maximal tumor uptake at 6 h. Tumor shrinkage mechanisms: Combination of vascular damage and direct tumor cell killing. Inflammatory response: Prominent neutrophil infiltration and intratumoral hemorrhage in PDT-treated tumors. Fluorescence properties: Hypericin absorption peaks at 470, 545, and 595 nm; fluorescence emission peaks at 590 and 640 nm. | Maximal tumor regression observed when light irradiation occurred 6 h post-hypericin injection. Comparable tumor RRP observed at 1 h and 6 h PDT intervals (p = 0.122).PDT at all intervals significantly inhibited tumor growth compared with controls (p < 0.001). Tumor necrosis, morphological changes, and significant inflammatory cell infiltration were evident in PDT-treated tumors. No anti-tumor effects with hypericin or light alone. | Not explicitly reported in the provided text. |
Du et al. (2004) [31] | HK1 CNE-2 NPC cells | Evaluation of the effect of HY-PDT on GST activity in NPC cells. | HY-PDT induces ROS, including superoxide anion radicals and hydroxyl radicals. ROS-mediated oxidative stress downregulates GST activity. Impact of reduced GST activity on cell viability and tumor response to PDT. | Significant reduction in GST activity in vitro (HK1: 27% of baseline; CNE-2: 60% of baseline). In vivo GST activity in HK1 tumors significantly decreased at 16 and 24 h post-PDT. PDT induced 69% and 53% cell death in HK1 and CNE-2 cells, respectively. | Not reported in the study. |
Head et al. (2006) [32] | HNSCC | Evaluating HY-PDT for tumor imaging and treatment, optimizing conditions for phototoxicity in vitro and testing its application in vivo in a mouse model. | Hypericin is activated by visible and near-infrared laser light to generate singlet oxygen and reactive oxygen species, leading to tumor cell death. Optimal phototoxic effects were observed at a laser wavelength of 593 nm, corresponding to hypericin’s absorption maximum. Hypericin localized in tumors, remaining effective for up to 10 days post-injection, as confirmed by fluorescence imaging using fiberoptic lasers. | In vitro HY-PDT showed a dose–response relationship, with significant tumoricidal effects at 0.2–0.5 μg/mL and enhanced cytotoxicity at 593 nm with 150 mW laser power. In vivo: Tumors under 0.4 cm2 responded well to biweekly hypericin PDT, showing regression. Larger tumors exhibited partial response or regrowth, highlighting the limitations of light penetration at 532 nm. The study suggested hypericin as a valuable agent for defining and sterilizing tumor margins during resection. | While the study reported no systemic toxicity, it highlighted challenges with light penetration in larger tumors, necessitating advancements in laser technology or treatment strategies. |
Olek et al. (2023) [23] | OSCC | Investigating the immunomodulatory effects of HY-PDT on cancer cells (SCC-25) and healthy gingival fibroblasts (HGF-1). | HY-PDT employs light-activated hypericin to induce oxidative stress via reactive oxygen species, leading to cell death. HY-PDT modulates cytokine secretion, affecting inflammatory and immunosuppressive pathways. Specific cytokines (e.g., IL-6, IL-8, IL-20, PTX3) and soluble receptors (e.g., sIL-6R) were evaluated for their response to PDT. | HY-PDT demonstrated cytotoxicity toward both cancer cells and fibroblasts, starting at a light dose of 5 J/cm2 and increasing with higher doses. Cytokine analysis revealed significant alterations, as follows: Increased secretion of IL-20 and sIL-6Rbeta in cancer cells following HY-PDT, enhanced IL-8 secretion with hypericin alone (no irradiation) for both cell lines, and reduced PTX3 secretion post-PDT in cancer cells. HY-PDT did not significantly alter IL-6 or IL-10 secretion. | Lack of selectivity for cancer cells, with observed cytotoxicity toward healthy fibroblasts, indicating potential for off-target effects. |
Olek et al. (2024) [24] | OSCC SCC-25 | Investigating the effects of HY-PDT on the secretion of soluble TNF receptors (sTNF-R1 and sTNF-R2) by SCC-25 and healthy gingival fibroblasts (HGF-1). | HY-PDT generates cytotoxic effects via reactive oxygen species and modulates immune responses. The role of TNF-α signaling and its soluble receptors in inflammation and immune modulation were examined. Secretion of soluble TNF-α receptors was measured after sublethal PDT doses in order to understand immunomodulatory effects. | HY-PDT increased sTNF-R1 secretion by SCC-25 after sublethal doses, with no effect on sTNF-R1 production in fibroblasts. PDT had no effect on sTNF-R2 secretion in either cell line. Cytotoxic effects of HY-PDT were dependent on the dose of hypericin and light. | PDT-induced cytotoxicity was not selective for cancer cells, indicating potential harm to healthy tissues at higher doses. |
Sharma et al. (2012) [33] | Non-melanoma cutaneous SCC | Investigating the efficacy of HY-PDT and its mode of cell death in SCC cell cultures, with a focus on optimizing treatment through a “double-hit” (two-day) strategy. | Hypericin is activated by UV light (320–400 nm) to produce ROS, leading to tumor cell death. Cell death was primarily necrotic and caspase-independent, differing from apoptosis. ROS levels peaked after the first day of treatment and decreased on the second day. | A significant dose-dependent reduction in SCC cell viability was observed after two days of HY-PDT treatment. Necrotic cell death was associated with increased ROS production on the first day. The “double-hit” treatment strategy was more effective in reducing cell viability compared with a single treatment. | Potential activation of inflammatory mediators due to necrotic cell death, which might contribute to tumor-specific immunity, although this was not directly measured in the study. |
Laffers et al. (2015) [34] | HNSCC—cell line FaDu | Investigating HY-PDT on HNSCC cells (FaDu cell line) in vitro, focusing on metabolic activity and apoptotic pathways. | Hypericin accumulates in tumor cells and is activated by light (450–700 nm), generating ROS. Hypericin-mediated PDT induces apoptosis and/or necrosis through caspase-dependent and independent pathways. Activation of hypericin results in damage to mitochondria, endoplasmic reticulum, and Golgi apparatus, initiating cell death. | FaDu cells treated with hypericin (5–50 µM) and illuminated for 10–25 min showed a significant reduction (92–97%) in metabolic activity after 1–8 days. Apoptosis was detected in nearly all cells treated with hypericin and light, with no apoptosis observed in untreated or non-illuminated cells. Higher hypericin concentrations and longer light exposure did not yield significantly greater effects, indicating efficiency at low doses and short exposure. | Hypericin treatment requires light activation; no dark toxicity was observed. Potential inflammation due to necrosis was not assessed in detail but is a consideration for future studies. |
Wozniak et al. (2023) [35] | SCC-25 cells and MUG-Mel2 | Investigating the selectivity and phototoxic effects of HY-PDT on melanoma (MUG-Mel2) and squamous cell carcinoma (SCC-25) compared with normal keratinocytes (HaCaT). | Hypericin is activated by orange light (590 nm), producing ROS that lead to cytotoxic effects. Cellular uptake of hypericin was assessed, showing selective accumulation in cancer cells. Apoptosis induction was evaluated using TUNEL assays and morphological changes. | PDT with hypericin showed higher phototoxicity in cancer cells (MUG-Mel2 and SCC-25) than in normal keratinocytes. A dose of 1 µM hypericin combined with orange light irradiation significantly reduced viability, as follows: MUG-Mel2: 21% cell viability; SCC-25: 20% cell viability; HaCaT: 26% cell viability. Apoptosis was observed in 52% of MUG-Mel2 cells and 23% of SCC-25 cells post-PDT. Morphological analysis revealed apoptotic changes such as cell rounding and detachment. | Minimal phototoxicity was noted in normal cells compared with cancer cells, suggesting a promising therapeutic window. Limitations include hypericin’s poor solubility and sensitivity to environmental factors, which may affect its application. |
Xu et al. (2010) [25] | NPC/ CNE-2 cells | Evaluating the efficacy of HY-PDT in inducing cell destruction and apoptosis in CNE-2 cells. | Hypericin is activated by red light (590 nm) to generate ROS, leading to apoptosis and cell death. The study explored early and late apoptosis using Hoechst staining for nuclear changes and flow cytometry with annexin V and PI. Two apoptotic pathways were considered: mitochondria-dependent and death receptor-dependent. | HY-PDT resulted in dose-dependent cytotoxicity based on both drug concentration (0–2.5 μM) and light fluence (1–8 J/cm2). Early apoptosis was identified as the primary mode of cell death, with an early apoptotic rate of 53.08% and late apoptosis at 6.77%. Cellular destruction included membrane blebbing, cell shrinkage, and nuclear condensation. | No significant cytotoxicity was observed in the absence of light, indicating hypericin’s safety without photoactivation. |
Author/Year | Light Source | Operating Mode | Wavelength (nm) | Energy Density (Fluence) (J/cm2) | Power Output (mW) | Powermeter Used | Irradiation Time (s) |
---|---|---|---|---|---|---|---|
Bhuvaneswari et al. (2007) [26] | Halogen light source (Zeiss KL1500) | Filtered bandpass light | 560–640 | 120 | 50 | Yes | Not specified |
Blank et al. (2001) [27] | Polychromatic visible light | Not specified | 560 | 60 | Not specified | Not specified | 20 min |
Bublik et al. (2006) [28] | Pulsed dye laser Ti:Sapphire laser | Pulsed, two-photon | 514, 550, 593 | 1–9 | 50, 100, 150 | Not specified | 0–120 |
Du et al. (2002) [29] | Fluorescence tubes (Phillips type OSRAM L30w11–860) with acetate filter | Wide illumination band | Above 585 | 0.5 | 30 | Not specified | Not specified |
Du et al. (2003) [30] | Halogen lamp with red acetate filter | Wide illumination band | Above 590 | 120 | 360 | Yes | Not specified |
Du et al. (2004) [31] | In vitro: Bank of fluorescent tubes (Phillips type OSRAM L30w11–860, 30 W) In vivo: Halogen lamp (360 W, Osram, Mexico) | Continuous mode | Above 585 | In vitro: 0.5 J/cm2 In vivo: 120 J/cm2 | 226 | Not specified | Not specified |
Head et al. (2006) [32] | KTP532 laser | Green light, fiberoptic delivery | 532, 550, 593 | 0–60 | 50, 100, 150 | Not specified | 0–120 |
Olek et al. (2023) [23] | TP-1 PDT lamp | Orange and infrared light filters | 580–720 | 0–20 | 35 mW/cm2. | Not specified | Automatically controlled |
Olek et al. (2024) [24] | PDT TP1 photodynamic lamp | Incoherent | 580–720 | 0, 1, 2, 5, 10, 20 | 35 mW/cm2. | Not specified | Automatically controlled |
Sharma et al. (2012) [33] | PUVA lamps (F15W/T8) | Continuous | 315–400 | 1 | Not specified | Not specified | Not specified |
Laffers et al. (2015) [34] | HQI®-TS lamp (Osram) | 450–700 nm spectrum | 450, 548, ~600 | Not specified | 50,000 lx | Not specified | 0, 600, 1500 |
Wozniak et al. (2023) [35] | Halogen lamp (Penta lamps) | Orange light | 590 | 3.6, 7.2 | 120 | Not specified | 30, 60 |
Xu et al. (2010) [25] | 400-watt quartz-halogen lamp | 590 nm long-pass filter | 590 | 1–8 | 8 | Yes | Not specified |
Author and Year | Incubation Time (Minutes) | Concentration/s of Hypericin Used |
---|---|---|
Bhuvaneswari et al. (2007) [26] | 360 | 5 mg/mL |
Blank et al. (2001) [27] | 30 | Not specified |
Bublik et al. (2006) [28] | 60 | 0.05 to 1 µg/mL |
Du et al. (2002) [29] | HK1: 240 CNE-2: 360 | 0.5, 1 µM |
Du et al. (2003) [30] | Not specified | 1 mg/mL |
Du et al. (2004) [31] | HK1: 240 CNE-2: 360 | In vitro: 0.5 µM In vivo: 2 mg/kg |
Head et al. (2006) [32] | 60 | Varied micromolar range |
Olek et al. (2023) [23] | 120 | 0, 0.25, 0.5, 1 µM |
Olek et al. (2024) [24] | 120 | 0, 0.25, 0.5, 1 µM |
Sharma et al. (2012) [33] | 240 | 0–7 mM |
Laffers et al. (2015) [34] | 150 | 0, 5, 10, 25, and 50 μM |
Wozniak et al. (2023) [35] | 120 | 0.1, 0.5, 1, 2.5, 5 µM |
Xu et al. (2010) [25] | 120 | 0–2.5 μM |
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Fiegler-Rudol, J.; Zięba, N.; Turski, R.; Misiołek, M.; Wiench, R. Hypericin-Mediated Photodynamic Therapy for Head and Neck Cancers: A Systematic Review. Biomedicines 2025, 13, 181. https://doi.org/10.3390/biomedicines13010181
Fiegler-Rudol J, Zięba N, Turski R, Misiołek M, Wiench R. Hypericin-Mediated Photodynamic Therapy for Head and Neck Cancers: A Systematic Review. Biomedicines. 2025; 13(1):181. https://doi.org/10.3390/biomedicines13010181
Chicago/Turabian StyleFiegler-Rudol, Jakub, Natalia Zięba, Radosław Turski, Maciej Misiołek, and Rafał Wiench. 2025. "Hypericin-Mediated Photodynamic Therapy for Head and Neck Cancers: A Systematic Review" Biomedicines 13, no. 1: 181. https://doi.org/10.3390/biomedicines13010181
APA StyleFiegler-Rudol, J., Zięba, N., Turski, R., Misiołek, M., & Wiench, R. (2025). Hypericin-Mediated Photodynamic Therapy for Head and Neck Cancers: A Systematic Review. Biomedicines, 13(1), 181. https://doi.org/10.3390/biomedicines13010181