Photodynamic Therapy (PDT) in Oncology Juarranz, Ángeles; Gilaberte, Yolanda; González, Salvador
Cancers,
11/2020, Letnik:
12, Številka:
11
Journal Article
Recenzirano
Odprti dostop
The issue is focused on Photodynamic Therapy (PDT), which is a minimally invasive therapeutic modality approved for treatment of several types of cancer and non-oncological disorders ...
Nowadays, one of the most exciting applications of nanotechnology in biomedicine is the development of localized, noninvasive therapies for diverse diseases, such as cancer. Among them, ...nanoparticle‐based photothermal therapy (PTT), which destroys malignant cells by delivering heat upon optical excitation of nanoprobes injected into a living specimen, is emerging with great potential. Two main milestones that must be reached for PTT to become a viable clinical treatment are deep penetration of the triggering optical excitation and real‐time accurate temperature monitoring of the ongoing therapy, which constitutes a critical factor to minimize collateral damage. In this work, a yet unexplored capability of near‐infrared emitting semiconductor nanocrystals (quantum dots, QDs) is demonstrated. Temperature self‐monitored QD‐based PTT is presented for the first time using PbS/CdS/ZnS QDs emitting in the second biological window. These QDs are capable of acting, simultaneously, as photothermal agents (heaters) and high‐resolution fluorescent thermal sensors, making it possible to achieve full control over the intratumoral temperature increment during PTT. The differences observed between intratumoral and surface temperatures in this comprehensive investigation, through different irradiation conditions, highlight the need for real‐time control of the intratumoral temperature that allows for a dynamic adjustment of the treatment conditions in order to maximize the efficacy of the therapy.
PbS/CdS/ZdS quantum dots (QDs) allow intratumoral temperature feedback in real time during photothermal therapy because of their temperature‐sensitive fluorescence emission in the second biological window and their remarkable photothermal conversion efficiency. Continuous monitoring of the intratumoral temperature, which differs greatly from that at the surface during the treatment, makes dynamic control of the therapy to maximize its efficacy possible.
Keratinocyte carcinomas (KCs) are the most prevalent form of cancer worldwide, and their incidence is rising dramatically, with an increasing trend in recent years ....
Over the past decade, near‐infrared (NIR)‐emitting nanoparticles have increasingly been investigated in biomedical research for use as fluorescent imaging probes. Here, high‐quality water‐dispersible ...core/shell/shell PbS/CdS/ZnS quantum dots (hereafter QDs) as NIR imaging probes fabricated through a rapid, cost‐effective microwave‐assisted cation exchange procedure are reported. These QDs have proven to be water dispersible, stable, and are expected to be nontoxic, resulting from the growth of an outer ZnS shell and the simultaneous surface functionalization with mercaptopropionic acid ligands. Care is taken to design the emission wavelength of the QDs probe lying within the second biological window (1000–1350 nm), which leads to higher penetration depths because of the low extinction coefficient of biological tissues in this spectral range. Furthermore, their intense fluorescence emission enables to follow the real‐time evolution of QD biodistribution among different organs of living mice, after low‐dose intravenous administration. In this paper, QD platform has proven to be capable (ex vivo and in vitro) of high‐resolution thermal sensing in the physiological temperature range. The investigation, together with the lack of noticeable toxicity from these PbS/CdS/ZnS QDs after preliminary studies, paves the way for their use as outstanding multifunctional probes both for in vitro and in vivo applications in biomedicine.
Low‐dose in vivo near‐infrared (NIR) fluorescence imaging is achieved by using carefully designed PbS/CdS/ZnS quantum dots (QDs), intensely emitting within the second biological window (1000–1350 nm). Moreover, preliminary studies both in vitro and in vivo have proven the lack of noticeable toxicity of these QDs. As an additional advantage, this NIR‐fluorescence imaging platform has demonstrated useful multifunctionality, thus being capable, both ex vivo and in vitro, of high‐resolution thermal sensing in the physiological temperature range.
Non-melanoma skin cancer (NMSC) is the most common form of cancer in the Caucasian population. Among NMSC types, basal cell carcinoma (BCC) has the highest incidence and squamous cell carcinoma (SCC) ...is less common although it can metastasize, accounting for the majority of NMSC-related deaths. Treatment options for NMSC include both surgical and non-surgical modalities. Even though surgical approaches are most commonly used to treat these lesions, Photodynamic Therapy (PDT) has the advantage of being a non-invasive option, and capable of field treatment, providing optimum cosmetic outcomes. Numerous clinical research studies have shown the efficacy of PDT for treating pre-malignant and malignant NMSC. However, resistant or recurrent tumors appear and sometimes become more aggressive. In this sense, the enhancement of PDT effectiveness by combining it with other therapeutic modalities has become an interesting field in NMSC research. Depending on the characteristics and the type of tumor, PDT can be applied in combination with immunomodulatory (Imiquimod) and chemotherapeutic (5-fluorouracil, methotrexate, diclofenac, or ingenol mebutate) agents, inhibitors of some molecules implicated in the carcinogenic process (COX2 or MAPK), surgical techniques, or even radiotherapy. These new strategies open the way to a wider improvement of the prevention and eradication of skin cancer.
Intracellular parasites can alter the cellular machinery of host cells to create a safe haven for their survival. In this regard, microsporidia are obligate intracellular fungal parasites with ...extremely reduced genomes and hence, they are strongly dependent on their host for energy and resources. To date, there are few studies into host cell manipulation by microsporidia, most of which have focused on morphological aspects. The microsporidia Nosema apis and Nosema ceranae are worldwide parasites of honey bees, infecting their ventricular epithelial cells. In this work, quantitative gene expression and histology were studied to investigate how these two parasites manipulate their host's cells at the molecular level. Both these microsporidia provoke infection-induced regulation of genes involved in apoptosis and the cell cycle. The up-regulation of buffy (which encodes a pro-survival protein) and BIRC5 (belonging to the Inhibitor Apoptosis protein family) was observed after infection, shedding light on the pathways that these pathogens use to inhibit host cell apoptosis. Curiously, different routes related to cell cycle were modified after infection by each microsporidia. In the case of N. apis, cyclin B1, dacapo and E2F2 were up-regulated, whereas only cyclin E was up-regulated by N. ceranae, in both cases promoting the G1/S phase transition. This is the first report describing molecular pathways related to parasite-host interactions that are probably intended to ensure the parasite's survival within the cell.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Sun overexposure leads to higher risk of photoaging and skin cancer. The contribution of infrared (IR) and visible light (VIS) radiation is currently being taken into account in their pathogenesis. ...Erythema, hyperpigmentation, genotoxicity or the increase of matrix metalloproteinases (MMPs) expression are some of the effects induced by these types of radiation. Extracts of various botanicals endowed with antioxidant activity are emerging as new photoprotective compounds. A natural extract from
(Fernblock
, FB) has antioxidant and photoprotective properties and exhibits a strong anti-aging effect. In this study, we evaluated the protective capacity of FB against the detrimental effects of infrared A (IRA) and VIS radiation in human dermal fibroblasts. We analyzed the effects of FB on the morphology, viability, cell cycle and expression of extracellular matrix components of fibroblasts subjected to VIS and IRA. Our results indicate that FB prevents cell damage caused by VIS and IRA. Moreover, it reduces the increase in MMP-1 and cathepsin K expression induced by both VIS and IRA radiation, and curbs alterations in fibrillin 1, fibrillin 2 and elastin expression. All these findings support FB as a feasible approach to prevent or treat skin damage caused by IRA or VIS exposure.
The role of reactive oxygen species (ROS) in the regulation of hair follicle (HF) cycle and skin homeostasis is poorly characterized. ROS have been traditionally linked to human disease and aging, ...but recent findings suggest that they can also have beneficial physiological functions in vivo in mammals. To test this hypothesis, we transiently switched on in situ ROS production in mouse skin. This process activated cell proliferation in the tissue and, interestingly, in the bulge region of the HF, a major reservoir of epidermal stem cells, promoting hair growth, as well as stimulating tissue repair after severe burn injury. We further show that these effects were associated with a transient Src kinase phosphorylation at Tyr416 and with a strong transcriptional activation of the prolactin family 2 subfamily c of growth factors. Our results point to potentially relevant modes of skin homeostasis regulation and demonstrate that a local and transient ROS production can regulate stem cell and tissue function in the whole organism.
For decades, the possibility to generate Reactive Oxygen Species (ROS) in biological systems through the use of light was mainly restricted to the photodynamic effect: the photoexcitation of ...molecules which then engage in charge- or energy-transfer to molecular oxygen (O
) to initiate ROS production. However, the classical photodynamic approach presents drawbacks, like
chemical reactivity of the photosensitizing agent or fast molecular photobleaching due to
ROS generation, to name a few. Recently, a new approach, which promises many advantages, has entered the scene: plasmon-driven hot-electron chemistry. The effect takes advantage of the photoexcitation of plasmonic resonances in metal nanoparticles to induce a new cohort of photochemical and redox reactions. These metal photo-transducers are considered chemically inert and can undergo billions of photoexcitation rounds without bleaching or suffering significant oxidative alterations. Also, their optimal absorption band can be shape- and size-tailored in order to match any of the near infrared (NIR) biological windows, where undesired absorption/scattering are minimal. In this mini review, the basic mechanisms and principal benefits of this light-driven approach to generate ROS will be discussed. Additionally, some significant experiments
and
will be presented, and tentative new avenues for further research will be advanced.
Exposure to sun radiation leads to higher risk of sunburn, pigmentation, immunosuppression, photoaging and skin cancer. In addition to ultraviolet radiation (UVR), recent research indicates that ...infrared radiation (IR) and visible light (VIS) can play an important role in the pathogenesis of some of these processes. Detrimental effects associated with sun exposure are well known, but new studies have shown that DNA damage continues to occur long after exposure to solar radiation has ended. Regarding photoprotection strategies, natural substances are emerging for topical and oral photoprotection. In this sense, Fernblock
, a standardized aqueous extract of the fern
(PLE), has been widely administered both topically and orally with a strong safety profile. Thus, this extract has been used extensively in clinical practice, including as a complement to photodynamic therapy (PDT) for treating actinic keratoses (AKs) and field cancerization. It has also been used to treat skin diseases such as photodermatoses, photoaggravated inflammatory conditions and pigmentary disorders. This review examines the most recent developments in the clinical application of Fernblock
and assesses how newly investigated action mechanisms may influence its clinical use.