Photodynamic therapy (PDT) is a method of cancer treatment that leads to the disintegration of cancer cells and has developed significantly in recent years. The clinically used photosensitizers are primarily porphyrin, which absorbs light in the red spectrum and their absorbance maxima are relatively short. This review presents group of compounds and their derivatives that are considered to be potential photosensitizers in PDT. Cyanine dyes are compounds that typically absorb light in the visible to near-infrared-I (NIR-I) spectrum range (750-900 nm). This meta-analysis comprises the current studies on cyanine dye derivatives, such as indocyanine green (so far used solely as a diagnostic agent), heptamethine and pentamethine dyes, squaraine dyes, merocyanines and phthalocyanines. The wide array of the cyanine derivatives arises from their structural modifications (e.g., halogenation, incorporation of metal atoms or organic structures, or synthesis of lactosomes, emulsions or conjugation). All the following modifications aim to increase solubility in aqueous media, enhance phototoxicity, and decrease photobleaching. In addition, the changes introduce new features like pH-sensitivity. The cyanine dyes involved in photodynamic reactions could be incorporated into sets of PDT agents.

Potential of Cyanine Derived Dyes in Photodynamic Therapy.

The presence of rare but highly tumorigenic cancer stem cells (CSCs) within the tumors is recognized as one of the major reasons of failure of conventional chemotherapies, mainly attributed to the development of drug resistance and increasing metastatic potential. Here, we propose a therapeutic strategy based on the simultaneous delivery of docetaxel (DTX) and the photosensitizer meso-tetraphenyl chlorine disulfonate (TPCS2a) using hyaluronic acid (HA) coated polymeric nanoparticles (HA-NPs) for the targeting and killing of CD44 over-expressing breast cancer (BC) cells, both differentiated and CSCs (CD44high/CD24low population), thus combining chemotherapy and photodynamic therapy (PDT). Using the CD44high MDA-MB-231 and the CD44low MCF-7 cells, we demonstrated the occurrence of CD44-mediated uptake of HA-NPs both in monolayers and mammosphere cultures enriched in CSCs. Cell treatments showed that combination therapy using co-loaded NPs (HA@DTX/TPCS2a-NPs) had superior efficacy over monotherapies (HA@DTX-NPs or HA@TPCS2a-NPs) in reducing the self-renewal capacity, measured as mammosphere formation efficiency, and in eradicating the CSC population evaluated with aldehyde dehydrogenase activity assay and CD44/CD24 immunostaining. In summary, these in vitro studies demonstrated for the first time the potential of the combination of DTX-chemotherapy and TPCS2a-PDT for killing CSCs using properly designed NPs.

https://www.mdpi.com/2072-6694/12/2/278/pdf

CD44 Targeting Mediated by Polymeric Nanoparticles and Combination of Chlorine TPCS2a-PDT and Docetaxel-Chemotherapy for Efficient Killing of Breast Differentiated and Stem Cancer Cells In Vitro

Peritoneal carcinomatosis occurs frequently in patients with advanced stage gastrointestinal and gynecological cancers. The wide-spread peritoneal micrometastases indicate a poor outlook, as the tumors are difficult to diagnose and challenging to completely eradicate with cytoreductive surgery and chemotherapeutics. Photodynamic diagnosis (PDD) and therapy (PDT), modalities that use photosensitizers for fluorescence detection or photochemical treatment of cancer, are promising theranostic approaches for peritoneal carcinomatosis. This review discusses the leading clinical trials, identifies the major challenges, and presents potential solutions to advance the use of PDD and PDT for the treatment of peritoneal carcinomatosis. While PDD for fluorescence-guided surgery is practically feasible and has achieved clinical success, large randomized trials are required to better evaluate the survival benefits. Although PDT is feasible and combines well with clinically used chemotherapeutics, poor tumor specificity has been associated with severe morbidity. The major challenges for both modalities are to increase the tumor specificity of the photosensitizers, to efficiently treat peritoneal microtumors regardless of their phenotypes, and to improve the ability of the excitation light to reach the cancer tissues. Substantial progress has been achieved in (1) the development of targeted photosensitizers and nanocarriers to improve tumor selectivity, (2) the design of biomodulation strategies to reduce treatment heterogeneity, and (3) the development of novel light application strategies. The use of X-ray-activated PDT during whole abdomen radiotherapy may also be considered to overcome the limited tissue penetration of light. Integrated approaches that take advantage of PDD, cytoreductive surgery, chemotherapies, PDT, and potentially radiotherapy, are likely to achieve the most effective improvement in the management of peritoneal carcinomatosis.

https://www.hal.inserm.fr/inserm-02974925/document

Photodynamic Diagnosis and Therapy for Peritoneal Carcinomatosis: Emerging Perspectives.

Aluminum chloride phthalocyanine in MCF-7: Rationally accounting for state of aggregation of photosensitizers inside cells

A pH-responsive drug delivery system (DDS) based on mesoporous silica nanoparticles (MSNs) has been prepared for the delivery of three anticancer drugs with different modes of action. The novelty of this system is its ability to combine a synergistic chemotherapy and photodynamic therapy. Herein, a photoactive conjugate of a phthalocyanine (Pc) and a topoisomerase I inhibitor (topo-I), namely camptothecin (CPT), linked by a polyethylene glycol (PEG) chain has been synthesized and then loaded into the mesopores of MSNs. Doxorubicin (DOX), which is a topoisomerase II inhibitor (topo-II), has also been covalently anchored to the outer surface of the MSNs through a dihydrazide polyethylene glycol linker. In the acidic environment of tumor cells, selective release of the three drugs takes place. In vitro studies have demonstrated the endocytosis of the system into HeLa and HepG2 cells and the subsequent release of the three drugs into the cytoplasm and nucleus. Furthermore, the cytotoxic effect of DOX, CPT and Pc has been assessed in vitro before and upon light irradiation.

Nanoparticles for Triple Drug Release for Combined Chemo- and Photodynamic Therapy

Limited cellular delivery and internalization efficiency of Al(III) phthalocyanine chloride tetrasulfonic acid (AlPcS4) induce poor penetration ability in cells and a slight photodynamic therapy (PDT) effect on gastric cancer. The combination treatment of AlPcS4/PDT with low‑dose chemotherapeutic agents may provide a promising treatment strategy to increase the weak delivery efficiency of AlPcS4, reducing the dose of chemical agents without reducing efficacy, and improving apoptosis‑inducing abilities, thereby increasing the antitumor effects and decreasing the noxious side effects on gastric cancer. We investigated and compared the synergistic antitumor growth effect on gastric cancer cells by combining AlPcS4/PDT treatment with different low‑dose chemotherapeutic agents, namely, 5‑fluorouracil (5‑FU), doxorubicin (DOX), cisplatin (CDDP), mitomycin C (MMC), and vincristine (VCR). The inhibitory effect was increased in treatments that combined AlPcS4/PDT with all the aforementioned low‑dose chemotherapeutic agents, to a different extent. An evident synergistic effect was obtained in the combination treatment of AlPcS4/PDT with low‑dose 5‑FU, DOX, and MMC by increasing AlPcS4 intracellular uptake ability, improving apoptosis‑inducing abilities, and prolonging apoptosis‑inducing time. The low‑dose chemotherapeutic agents prolonged the apoptosis‑inducing period of AlPcS4/PDT, and AlPcS4/PDT quickly improved apoptosis‑inducing abilities of chemotherapy even at low doses. Generally, the combination treatment of AlPcS4/PDT with low‑dose chemotherapeutic agents had significant antitumor growth effects in addition to a low dark‑cytotoxicity effect on gastric cancer, thereby representing an effective and feasible therapy method for gastric cancer.

/pdf/comparison-of-the-synergistic-anticancer-activity-of-alpcs4-3r82ox1n4i.pdf

Comparison of the synergistic anticancer activity of AlPcS4 photodynamic therapy in combination with different low‑dose chemotherapeutic agents on gastric cancer cells

The invention provides a research system for liquid light induced breakdown and a cavitation effect. Laser lights emitted by a pumping source module and a detection source module are subjected to beam combination through a dichroscope A; a 50% spectroscope, a 40x objective lens, a sample cell, a dichroscope, a focusing lens and a photoelectric detector are arranged in sequence in a direction of the principal optical axis of the dichroscope A; a laser energy power meter is arranged in a vertical direction of the 50% spectroscope; objective lenses are clung to three walls of the sample cell, wherein a 10x objective lens is connected with a high-speed camera, and a vertical LED light source is arranged on another wall of the sample cell; the photoelectric detector is connected with a oscilloscope. The research system provided by the invention can realize nanosecond laser induced liquid light induced breakdown, image information of cavitation bubbles formed during breakdown is monitored in real time, and information of laser energy is recorded at the same time; the research system provides a direct theoretical direction and a practical support for selecting a laser dosage and a mode of action and estimating an action effect during laser medical treatment.

Research system for liquid light induced breakdown and cavitation effect

The invention discloses a device and method for collecting and segmenting of hyperspectral images of unstainedpathological sections. A section sample platform is supported in the middle of a bracket, the hyperspectral images of the unstainedpathological sectionsare automatically collected and processed through a computer, and lesion area segmentation resultsare obtained. Based on spectral difference caused by pathological changes of tissues, a personal computeris adopted to synchronously control relevant modules, spectral sequence images of the unstainedhistopathological sectionsare collected and preprocessed, and corresponding three-dimensionalhyperspectral dataare produced after overlaying;based the data and the combination with a currentlypopularneural network classificationthought, a spectral classification algorithm is developed to perform identity partitioning of a lesion area, thereby acceleratingthe identification rate and efficiency of the histopathological section, avoidingmanual errors which maybe brought during staining, and reducingthe time required by section making;automatic judgment is performed by utilizing a machine algorithm, therebyreducingsubjectivity caused by manual judgment. Therefore,a good auxiliary function is provided for a pathology doctor to detect the pathological sections.

Device and method for collecting and segmenting of hyperspectral images of unstainedpathological sections

The invention discloses a quick detection device and method for microbial aerosol in air. The device comprises a detection device, a switch and a display screen are arranged on the detection device, the upper portion of the detection device is provided with an air sampling entrance, a peripheral port is formed in the detection device, and the detection device is connected to a computer. According to the quick detection device and method for the microbial aerosol in air, surrounding space is sampled timely by the air sampling entrance, the pathogenic microbial aerosol in air environment can be monitored online and timely; besides, the remote control and online detection can be achieved due to the connection to network by the computer; the device saves lots of manpower and material resources, and has the advantages of being low in single detection cost and the like.

Quick detection device and method for microbial aerosol in air

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Comparison of the synergistic anticancer activity of AlPcS4 photodynamic therapy in combination with different low‑dose chemotherapeutic agents on gastric cancer cells

Research system for liquid light induced breakdown and cavitation effect

Device and method for collecting and segmenting of hyperspectral images of unstainedpathological sections

Quick detection device and method for microbial aerosol in air