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result(s) for
"Porphyrins"
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Application of Porphyrins in Antibacterial Photodynamic Therapy
by
Amos-Tautua, Bamidele
,
Songca, Sandile
,
Oluwafemi, Oluwatobi
in
Animals
,
Anti-Bacterial Agents - adverse effects
,
Anti-Bacterial Agents - chemistry
2019
Antibiotics are commonly used to control, treat, or prevent bacterial infections, however bacterial resistance to all known classes of traditional antibiotics has greatly increased in the past years especially in hospitals rendering certain therapies ineffective. To limit this emerging public health problem, there is a need to develop non-incursive, non-toxic, and new antimicrobial techniques that act more effectively and quicker than the current antibiotics. One of these effective techniques is antibacterial photodynamic therapy (aPDT). This review focuses on the application of porphyrins in the photo-inactivation of bacteria. Mechanisms of bacterial resistance and some of the current ‘greener’ methods of synthesis of meso-phenyl porphyrins are discussed. In addition, significance and limitations of aPDT are also discussed. Furthermore, we also elaborate on the current clinical applications and the future perspectives and directions of this non-antibiotic therapeutic strategy in combating infectious diseases.
Journal Article
Methane Formation Induced via Face-to-Face Orientation of Cyclic Fe Porphyrin Dimer in Photocatalytic COsub.2 Reduction
2024
Iron porphyrins are known to provide CH[sub.4] as an eight-electron reduction product of CO[sub.2] in a photochemical reaction. However, there are still some aspects of the reaction mechanism that remain unclear. In this study, we synthesized iron porphyrin dimers and carried out the photochemical CO[sub.2] reduction reactions in N,N-dimethylacetamide (DMA) containing a photosensitizer in the presence of 1,3-dimethyl-2-phenyl-2,3-dihydro-1H-benzo[d]imidazole (BIH) as an electron donor. We found that, despite a low catalytic turnover number, CH[sub.4] was produced only when these porphyrins were facing each other. The close proximity of the cyclic dimers, distinguishing them from a linear Fe porphyrin dimer and monomers, induced multi-electron CO[sub.2] reduction, emphasizing the unique role of their structural arrangement in CH[sub.4] formation.
Journal Article
In situ supramolecular polymerization-enhanced self-assembly of polymer vesicles for highly efficient photothermal therapy
2020
Vesicular photothermal therapy agents (PTAs) are highly desirable in photothermal therapy (PTT) for their excellent light-harvesting ability and versatile hollow compartments. However, up to now, the reported vesicular PTAs are generally self-assembled from small molecules like liposomes, and polymer vesicles have seldom been used as PTAs due to the unsatisfactory photothermal conversion efficiency resulting from the irregular packing of chromophores in the vesicle membranes. Here we report a nano-sized polymer vesicle from hyperbranched polyporphyrins with favorable photothermal stability and extraordinarily high photothermal efficiency (44.1%), showing great potential in imaging-guided PTT for tumors through in vitro and in vivo experiments. These excellent properties are attributed to the in situ supramolecular polymerization of porphyrin units inside the vesicle membrane into well-organized 1D monofilaments driven by π–π stacking. We believe the supramolecular polymerization-enhanced self-assembly process reported here will shed a new light on the design of supramolecular materials with new structures and functions.
Photothermal therapy (PTT) has recently emerged as a promising approach for cancer therapy. Here, the authors report a hyperbranched polymer vesicle with favorable photothermal stability and high photothermal efficiency for PTT through a supramolecular polymerization-enhanced self-assembly strategy.
Journal Article
Chemical approaches for the enhancement of porphyrin skeleton-based photodynamic therapy
by
Bai, Renren
,
Zhou, Tao
,
Xie, Yuanyuan
in
Animals
,
anti-cancer
,
Antineoplastic Agents - chemical synthesis
2020
With the development of photodynamic therapy (PDT), remarkable studies have been conducted to generate photosensitisers (PSs), especially porphyrin PSs. A variety of chemical modifications of the porphyrin skeleton have been introduced to improve cellular delivery, stability, and selectivity for cancerous tissues. This review aims to highlight the developments in porphyrin-based structural modifications, with a specific emphasis on the role of PDT in anticancer treatment and the design of PSs to achieve a synergistic effect on multiple targets.
Journal Article
Nanozyme Decorated Metal-Organic Framework Nanosheet for Enhanced Photodynamic Therapy Against Hypoxic Tumor
2024
Photodynamic therapy (PDT) has attracted increasing attention in the clinical treatment of epidermal and luminal tumors. However, the PDT efficacy in practice is severely impeded by tumor hypoxia and the adverse factors associated with hydrophobic photosensitizers (PSs), including low delivery capacity, poor photoactivity and limited ROS diffusion. In this study, Pt nanozymes decorated two-dimensional (2D) porphyrin metal-organic framework (MOF) nanosheets (PMOF@HA) were fabricated and investigated to conquer the obstacles of PDT against hypoxic tumors.
PMOF@HA was synthesized by the coordination of transition metal iron (Zr
) and PS (TCPP), in situ generation of Pt nanozyme and surface modification with hyaluronic acid (HA). The abilities of hypoxic relief and ROS generation were evaluated by detecting the changes of O
and
O
concentration. The cellular uptake was investigated using flow cytometry and confocal laser scanning microscopy. The SMMC-7721 cells and the subcutaneous tumor-bearing mice were used to demonstrate the PDT efficacy of PMOF@HA in vitro and in vivo, respectively.
Benefiting from the 2D structure and inherent properties of MOF materials, the prepared PMOF@HA could not only serve as nano-PS with high PS loading but also ensure the rational distance between PS molecules to avoid aggregation-induced quenching, enhance the photosensitive activity and promote the rapid diffusion of generated radical oxide species (ROS). Meanwhile, Pt nanozymes with catalase-like activity effectively catalyzed intratumoral overproduced H
O
into O
to alleviate tumor hypoxia. Additionally, PMOF@HA, with the help of externally coated HA, significantly improved the stability and increased the cell uptake by CD44 overexpressed tumor cells to strengthen O
self-supply and PDT efficacy.
This study provided a new strategy of integrating 2D porphyrin MOF nanosheets with nanozymes to conquer the obstacles of PDT against hypoxic tumors.
Journal Article
Porphyrin as Diagnostic and Therapeutic Agent
by
Tsolekile, Ncediwe
,
Nelana, Simphiwe
,
Oluwafemi, Oluwatobi Samuel
in
Animals
,
Cancer
,
conjugate
2019
The synthesis and application of porphyrins has seen a huge shift towards research in porphyrin bio-molecular based systems in the past decade. The preferential localization of porphyrins in tumors, as well as their ability to generate reactive singlet oxygen and low dark toxicities has resulted in their use in therapeutic applications such as photodynamic therapy. However, their inherent lack of bio-distribution due to water insolubility has shifted research into porphyrin-nanomaterial conjugated systems to address this challenge. This has broadened their bio-applications, viz. bio-sensors, fluorescence tracking, in vivo magnetic resonance imaging (MRI), and positron emission tomography (PET)/CT imaging to photo-immuno-therapy just to highlight a few. This paper reviews the unique theranostic role of porphyrins in disease diagnosis and therapy. The review highlights porphyrin conjugated systems and their applications. The review ends by bringing current challenges and future perspectives of porphyrin based conjugated systems and their respective applications into light.
Journal Article
In situ conversion of porphyrin microbubbles to nanoparticles for multimodality imaging
2015
On exposure to low-frequency ultrasound, porphyrin microbubbles form nanoparticles that possess the same optical and therapeutic properties as the original microbubble, which can be used simultaneously for imaging and drug delivery.
Converting nanoparticles or monomeric compounds into larger supramolecular structures by endogenous
1
,
2
or external
3
,
4
stimuli is increasingly popular because these materials are useful for imaging and treating diseases. However, conversion of microstructures to nanostructures is less common. Here, we show the conversion of microbubbles to nanoparticles using low-frequency ultrasound. The microbubble consists of a bacteriochlorophyll–lipid shell around a perfluoropropane gas. The encapsulated gas provides ultrasound imaging contrast and the porphyrins in the shell confer photoacoustic and fluorescent properties. On exposure to ultrasound, the microbubbles burst and form smaller nanoparticles that possess the same optical properties as the original microbubble. We show that this conversion is possible in tumour-bearing mice and could be validated using photoacoustic imaging. With this conversion, our microbubble can potentially be used to bypass the enhanced permeability and retention effect when delivering drugs to tumours.
Journal Article
Disulfonated tetraphenyl chlorin (TPCS2a)-induced photochemical internalisation of bleomycin in patients with solid malignancies: a phase 1, dose-escalation, first-in-man trial
2016
Photochemical internalisation, a novel minimally invasive treatment, has shown promising preclinical results in enhancing and site-directing the effect of anticancer drugs by illumination, which initiates localised chemotherapy release. We assessed the safety and tolerability of a newly developed photosensitiser, disulfonated tetraphenyl chlorin (TPCS2a), in mediating photochemical internalisation of bleomycin in patients with advanced and recurrent solid malignancies.
In this phase 1, dose-escalation, first-in-man trial, we recruited patients (aged ≥18 to <85 years) with local recurrent, advanced, or metastatic cutaneous or subcutaneous malignancies who were clinically assessed as eligible for bleomycin chemotherapy from a single centre in the UK. Patients were given TPCS2a on day 0 by slow intravenous injection, followed by a fixed dose of 15 000 IU/m2 bleomycin by intravenous infusion on day 4. After 3 h, the surface of the target tumour was illuminated with 652 nm laser light (fixed at 60 J/cm2). The TPCS2a starting dose was 0·25 mg/kg and was then escalated in successive dose cohorts of three patients (0·5, 1·0, and 1·5 mg/kg). The primary endpoints were safety and tolerability of TPCS2a; other co-primary endpoints were dose-limiting toxicity and maximum tolerated dose. The primary analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00993512, and has been completed.
Between Oct 3, 2009, and Jan 14, 2014, we recruited 22 patients into the trial. 12 patients completed the 3-month follow-up period. Adverse events related to photochemical internalisation were either local, resulting from the local inflammatory process, or systemic, mostly as a result of the skin-photosensitising effect of TPCS2a. The most common grade 3 or worse adverse events were unexpected higher transient pain response (grade 3) localised to the treatment site recorded in nine patients, and respiratory failure (grade 4) noted in two patients. One dose-limiting toxicity was reported in the 1·0 mg/kg cohort (skin photosensitivity [grade 2]). Dose-limiting toxicities were reported in two of three patients at a TPCS2a dose of 1·5 mg/kg (skin photosensitivity [grade 3] and wound infection [grade 3]); thus, the maximum tolerated dose of TPCS2a was 1·0 mg/kg. Administration of TPCS2a was found to be safe and tolerable by all patients. No deaths related to photochemical internalisation treatment occurred.
TPCS2a-mediated photochemical internalisation of bleomycin is safe and tolerable. We identified TPCS2a 0·25 mg/kg as the recommended treatment dose for future trials.
PCI Biotech.
Journal Article
Enhanced Cellular Uptake and Photodynamic Effect with Amphiphilic Fluorinated Porphyrins: The Role of Sulfoester Groups and the Nature of Reactive Oxygen Species
2020
A class of amphiphilic photosensitizers for photodynamic therapy (PDT) was developed. Sulfonate esters of modified porphyrins bearing—F substituents in the ortho positions of the phenyl rings have adequate properties for PDT, including absorption in the red, increased cellular uptake, favorable intracellular localization, low cytotoxicity, and high phototoxicity against A549 (human lung adenocarcinoma) and CT26 (murine colon carcinoma) cells. Moreover, the role of type I and type II photochemical processes was assessed by fluorescent probes specific for various reactive oxygen species (ROS). The photodynamic effect is improved not only by enhanced cellular uptake but also by the high generation of both singlet oxygen and oxygen-centered radicals. All of the presented results support the idea that the rational design of photosensitizers for PDT can be further improved by better understanding the determinants affecting its therapeutic efficiency and explain how smart structural modifications can make them suitable photosensitizers for application in PDT.
Journal Article
Ranibizumab versus Verteporfin for Neovascular Age-Related Macular Degeneration
2006
Previous studies have implicated intravitreal vascular endothelial growth factor A (VEGF-A) as a target for countering neovascularization and, therefore, age-related macular degeneration. This double-blind, controlled trial comparing ranibizumab, which neutralizes all isoforms of VEGF-A, with photodynamic therapy with verteporfin showed that ranibizumab was better able to retard the progression of predominantly classic neovascular age-related macular degeneration.
This trial comparing ranibizumab with photodynamic therapy with verteporfin showed that ranibizumab was better able to retard the progression of predominantly classic neovascular age-related macular degeneration.
Age-related macular degeneration is a leading cause of severe and irreversible vision loss in the developed world among people 50 years of age or older.
1
–
4
The neovascular form of the disease is characterized by the growth of abnormal, choroidal blood vessels beneath the macula, which causes severe loss of vision.
5
Two main patterns of choroidal neovascularization that are associated with age-related macular degeneration, as seen on fluorescein angiography, are classic (in which intensely bright fluorescence is seen in early phases of the angiogram and leaks in late phases) and occult (in which leakage is less intense and appears in . . .
Journal Article