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.
Specially designed functionalized nanomaterials such as superparamagnetic iron oxide, gold, quantum dots and up- and down-conversion lanthanide series nanoparticles have consistently and completely revolutionized the biomedical environment over the past few years due to their specially inferring properties, such as specific drug delivery, plasmonic effect, optical and imaging properties, therapeutic thermal energy productionand excellent irresistible cellular penetration. These properties have been used to improve many existing disease treatment modalities and have led to the development of better therapeutic approaches for the advancement of the treatment of critical human diseases, such as cancers and related malaise. In photodynamic therapy, for example, where the delivery of therapeutic agents should ideally avoid toxicity on nearby healthy cells, superparamagnetic iron oxide nanoparticles have been shown to be capable of making photodynamic therapy (PDT) prodrugs and their associative targeting moieties tumor-specific via their unique response to an external magnetic fields. In this review, the nanomaterials commonly employed for the enhancement of photodynamic therapy are discussed. The review further describes the various methods of synthesis and characterization of these nanomaterials and highlights challenges for improving the efficacy of PDT in the future.
The toxicity of heavy metals present in binary semiconductor nanoparticles also known as quantum dots (QDs) has hindered their wide applications hence the advent of non-toxic ternary quantum dots. These new group of quantum dots have been shown to possess some therapeutic action against cancer cell lines but not significant enough to be referred to as an ideal therapeutic agent. In this report, we address this problem by conjugating red emitting CuInS/ZnS QDs to a 5,10,15,20-tetrakis(3hydroxyphenyl)porphyrin-photosensitizer for improved bioactivities. The glutathione capped CuInS/ ZnS QDs were synthesized in an aqueous medium using a kitchen pressure cooker at different Cu: In ratios (1:4 and 1:8) and at varied temperatures (95 °C, 190 °C and 235 °C). Optical properties show that the as-synthesized CuInS/ZnS QDs become red-shifted compared to the core (CuInS) after passivation with emission in the red region while the cytotoxicity study revealed excellent cell viability against normal kidney fibroblasts (BHK21). The highly fluorescent, water-soluble QDs were conjugated to 5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin (mTHPP) via esterification reactions at room temperature. The resultant water-soluble conjugate was then used for the cytotoxicity, fluorescent imaging and gene expression study against human monocytic leukemia cells (THP-1). Our result showed that the conjugate possessed high cytotoxicity against THP-1 cells with enhanced localized cell uptake compared to the bare QDs. In addition, the gene expression study revealed that the conjugate induced inflammation compared to the QDs as NFKB gene was over-expressed upon cell inflammation while the singlet oxygen (1 o 2) study showed the conjugate possessed large amount of 1 o 2 , three times than the bare porphyrin. Thus, the as-synthesized conjugate looks promising as a therapeutic agent for cancer therapy. The use of nanomaterials for biological application has in the past decade transpired as a promising avenue to explore for biological application due to their size, shape, specific surface area, aspect ratio and surface chemistry. Of the reported nanomaterial, semiconductor nanomaterials also known as quantum dots (QDs) still remain the most promising due to their excellent optoelectronic properties and spectral tunability which allows for their use in the ultraviolet and near infra-red region 1,2. These inherent properties have made QDs more appealing
Background
Photodynamic therapy (PDT) is a non-invasive treatment modality that destroys abnormally growing cells or microorganisms. Porphyrins are used as photosensitizers in PDT; however, their clinical application has been limited by their poor water solubility, resulting in aggregation and low quantum yields of reactive oxygen species (ROS).
Methods
To overcome these limitations and improve PDT efficacy, we herein report the conjugation of ZnCuInS/ZnS (ZCIS/ZnS) quantum dots (QDs) to 5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin (mTHPP). The optimal conditions for QDs porphyrin conjugation formation were systematically evaluated.
Discussion
This study further assessed the PDT efficacy and antibacterial potency of the synthesized ZCIS/ZnS-mTHPP conjugates. The PDT efficacy of the QDs, mTHPP, and conjugate was evaluated against the murine metastatic melanoma (B16 F10 Nex2) cell line. This was performed with and without LED irradiation.
Results
The conjugate exhibited the highest reduction in cell viability following LED irradiation (72%) compared to the bare QDs (19%) and mTHPP (1%). Antimicrobial studies conducted on
E. coli
showed that the conjugation exhibits a higher antibacterial effect than the bare QDs, even without light.
Conclusion
The results suggest that conjugate is a promising class of materials for anti-cancer and antimicrobial PDT.
Background
Metal-free, water-soluble and highly stable meso-tetra-(4-sulfonatophenyl) porphyrin (TPPS
4
) has been studied for their singlet oxygen quantum yield. However, TPPS
4
suffers from inherent shortcomings. To address these, TPPS
4
was conjugated to ternary copper indium sulphide/ zinc sulphide (CuInS
2
/ZnS) quantum dots (QDs).
Purpose
We herein report for the first time the synthesis of TPPS
4
–CuInS/ZnS QDs conjugate as an improved photosensitizer.
Methods
Water-soluble TPPS
4
was synthesized from tetraphenylporphyrin (TPPH
2
) after silica-gel purification. The CuInS/ZnS QDs were synthesized by hydrothermal method at a Cu:In ratio of 1:4. The porphyrin–QDs conjugate was formed via the daggling sulfonyl bond of the porphyrin and amine bond of the QDs. The effect of pH on the optical properties of TPPS
4
was evaluated. The effect of Zn:Cu + In ratio on the ZnS shell passivation was examined to reduce structural defects on the as-synthesized QDs.
Results:
Various spectroscopic techniques were used to confirm the successful conversion of the organic TPPH
2
to water-soluble TPPS
4
. The singlet oxygen generation evaluation shows an improved singlet oxygen quantum yield from 0.19 for the porphyrin (TPPS
4
) alone to 0.69 after conjugation (CuInS/ZnS-TPPS
4
) with an increase in the reaction rate constant (k (s-1)).
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