Protective effect of nanoemulsions containing CdTe quantum dots with potential application as a diagnostic agent.

A nanoemulsion containing CdTe quantum dots (NE-CdTe-QD) was developed to shield cells from cadmium toxicity and shown to be a promising candidate for brain tumor diagnosis. CdTe-QD was characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and Raman spectroscopy. CdTe-QD exhibited high luminescence emission at 700 nm, and their stability was maintained when encapsulated in lipidic/polymeric nanoemulsions (198 ± 2.0 nm; PDI = 0.174; - 49.0 mV). The biological effects of free and nanoemulsified CdTe-QD were tested in normal cells (NHF) and glioblastoma cell lines (U87-MG and T98G). Membrane colocalization of NE-CdTe-QD by T98G cells was observed. Instead, intracellular endoplasmic reticulum localization of NE-CdTe-QD was verified in U87-MG cells. Cell viability was reduced only when NE-CdTe-QD permeated the membrane of GBM cells, as observed in U87-MG cells, whereas no cytotoxic effects were observed in normal fibroblasts. Incorporating quantum dots directly into the brain cells is difficult. However, the nanoemulsions reduced the toxicity of CdTe-QD in zebrafish larvae and increased their circulation time, and direct injection into the zebrafish brain did not affect neural cell viability. This validates the potential application of these nanomaterials as diagnostic agents and satisfies the necessary criteria for their use as photosensitizers in photodynamic therapy.

Development of Liposomes Loaded with Chloroaluminum Phthalocyanine for Application of Photodynamic Therapy in Breast Cancer.

Chloraluminium phthalocyanine (ClAlPc) has potential therapeutic effect for the treatment of cancer; however, the molecule is lipophilic and may present self-aggregation which limits its clinical success. Thus, nanocarriers like liposomes can improve ClAlPc solubility, reduce off-site toxicity and increase circulation time. For this purpose, developing suitable liposomes requires the evaluation of different lipid compositions. Herein, we aimed to develop liposomes containing soy phosphatidylcholine (SPC), 1,2-distearoyl-sn-glycero- 3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPEPEG2000), cholesterol and oleic acid loaded with ClAlPc using the surface response methodology and the Box-Behnken design. Liposomes with particle size from 110.93 to 374.97 nm and PdI from 0.265 to 0.468 were obtained. The optimized formulation resulted in 69.09 % of ClAlPc encapsulated, with particle size and polydispersity index, respectively, at 153.20 nm and 0.309, providing stability and aggregation control. Atomic force microscopy revealed vesicles in a spherical or almost spherical shape, while the analyzes by Differential Scanning Calorimetry (DSC), Powder X-ray Diffraction (PXRD), and Fourier transform infrared spectroscopy (FTIR) suggested that the drug was adequately incorporated into the lipid bilayer of liposomes, in its amorphous state or molecularly dispersed. In vitro studies conducted in breast cancer cells (4T1) showed that liposome improved phototoxicity compared to the ClAlPc solution. ClAlPc-loaded liposomes also enhanced the production of ROS 3-fold compared to the ClAlPc solution. Finally, confocal microscopy and flow cytometry demonstrated the ability of the liposomes to enter cells and deliver the fluorescent ClAlPc photosensitizer with dose and time-dependent effects. Thus, this work showed that Box-Behnken factorial design was an effective strategy for optimizing formulation development. The obtained ClAlPc liposomes can be applied for photodynamic therapy in breast cancer cells.

Renal proximal tubule-on-a-chip in PDMS: fabrication, functionalization, and RPTEC:HUVEC co-culture evaluation.

'On-a-chip' technology advances the development of physiologically relevant organ-mimicking architecture by integrating human cells into three-dimensional microfluidic devices. This method also establishes discrete functional units, faciliting focused research on specific organ components. In this study, we detail the development and assessment of a convoluted renal proximal tubule-on-a-chip (PT-on-a-chip). This platform involves co-culturing Renal Proximal Tubule Epithelial Cells (RPTEC) and Human Umbilical Vein Endothelial Cells (HUVEC) within a polydimethylsiloxane microfluidic device, crafted through a combination of 3D printing and molding techniques. Our PT-on-a-chip significantly reduced high glucose level, exhibited albumin uptake, and simulated tubulopathy induced by amphotericin B. Remarkably, the RPTEC:HUVEC co-culture exhibited efficient cell adhesion within 30 min on microchannels functionalized with plasma, 3-aminopropyltriethoxysilane, and type-I collagen. This approach significantly reduced the required incubation time for medium perfusion. In comparison, alternative methods such as plasma and plasma plus polyvinyl alcohol were only effective in promoting cell attachment to flat surfaces. The PT-on-a-chip holds great promise as a valuable tool for assessing the nephrotoxic potential of new drug candidates, enhancing our understanding of drug interactions with co-cultured renal cells, and reducing the need for animal experimentation, promoting the safe and ethical development of new pharmaceuticals.

Core-shell structured carbon dots with up-conversion fluorescence and photo-triggered nitric oxide-releasing properties.

Cancer-targeted nanotechnology has a new trend in the design and preparation of new materials with functions for imaging and therapeutic applications simultaneously. As a new type of carbon nanomaterial, the inherent core-shell structured carbon dots (CDs) can be designed to provide a modular nanoplatform for integration of bioimaging and therapeutic capabilities. Here, core-shell structured CDs are designed and synthesized from levofloxacin and arginine and named Arg-CDs, in which levofloxacin-derived chromophores with up-conversion fluorescence are densely packed into the carbon core while guanidine groups are located on the shell, providing nitric oxide (NO) for photodynamic therapy of tumors. Moreover, the chromophores in the carbon core irradiated by visible LED light generate large amounts of reactive oxygen species (ROSs) that will oxidize the guanidine groups located on the shell of the Arg-CDs and further increase the NO releasing capacity remarkably. The as-synthesized Arg-CDs show excellent biocompatibility, bright up-conversion fluorescence, and a light-controlled ROS & NO releasing ability, which can be a potential light-modulated nanoplatform to integrate bioimaging and therapeutic functionalities.

Multi-charged nanoemulsion for photodynamic treatment of glioblastoma cell line in 2D and 3D in vitro models.

Multi-charged nanoemulsions (NE) were designed to deliver Cannabidiol (CBD), Indocyanine green (ICG), and Protoporphyrin (PpIX) to treat glioblastoma (GBM) through Photodynamic Therapy (PDT). The phase-inversion temperature (PIT) method resulted in a highly stable NE that can be scaled easily, with a six-month shelf-life. We observed the quasi-spherical morphology of the nanoemulsions without any unencapsulated material and that 89% (± 5.5%) of the material was encapsulated. All physicochemical properties were within the expected range for a nanostructured drug delivery system, making these multi-charged nanoemulsions promising for further research and development. NE-PIC (NE-Protoporphyrin + Indocyanine + CBD) was easily internalized on GBM cells after three hours of incubation. Nanoemulsion (NE and NE-PIC) did not result in significant cytotoxicity, even for GBM or non-tumorigenic cell lines (NHF). Phototoxicity was significantly higher for the U87MG cell than the T98G cell when exposed to: visible (430 nm) and infrared (810 nm) laser light, with a difference of about 20%. From 50 mJ.cm-2, the viability of GBM cell lines decreases significantly, ranging from 65% to 85%. The NE-PIC was also effective for inhibiting cell proliferation into a 3D spheroidal GBM cell model, which is promising for mimicking the tumor cell environment. Irradiation at 810 nm was more effective in treating spheroid due to its deeper penetration in complex structures. NE-PIC has the potential as a drug delivery system for photoinactivation and photo diagnostic of GBM cell lines, taking advantage of the versatility of its active components.

Hybrid lipid-biopolymer nanocarrier as a strategy for GBM photodynamic therapy (PDT).

Glioblastoma (GBM) is the most common brain cancer characterized by aggressive and infiltrated tumors. For this, hybrid biopolymer-lipid nanoparticles coated with biopolymers such as chitosan and lipidic nanocarriers (LN) loaded with a photosensitizer (AlClPc) can be used for GBM photodynamic therapy. The chitosan-coated LN exhibited stable physicochemical characteristics and presented as an excellent lipid nanocarrier with highly efficiently encapsulated photosensitizer chloro-aluminum phthalocyanine (AlClPc). LN(AlClPc)Ct0.1% in the presence of light produced more reactive oxygen species and reduced brain tumor cell viability and proliferation. Confirm the effects of in vivo LN applications with photodynamic therapy confirmed that the total brain tumor area decreased without systemic toxicity in mice. These results suggest a promising strategy for future clinical applications to improve brain cancer treatment.

Photo-activated autophagy-associated tumour cell death by lysosome impairment based on manganese-doped graphene quantum dots.

Autophagy is indispensable in normal cellular processes, yet detrimental to cancer treatment because it severely lowers the therapeutic efficiency. One of the keys to solve this problem may lie in lysosomes, which requires the rational design of nanomedicine that is capable of localizing and maintaining its efficacy in lysosomes. In this work, a facile and versatile nanoplatform based on manganese-doped graphene quantum dots (Mn-FGQDs) is developed for effective and precise photodynamic impairment of lysosomes. Specifically, the incorporation of Mn not only strengthens the generation capability of reactive oxygen species (ROS), but also facilitates its accumulation in lysosomes. Moreover, Mn-FGQDs are structurally robust and retain their high photodynamic efficiency in the lysosomal environment. On this basis, the light-triggered generation of ROS would primarily influence the function of lysosomes, leading to lysosome impairment and thereby effectively blocking the protective autophagy recycling. More impressively, a continuous increase in the oxidative stress level in lysosomes causes severe autophagy dysfunction, as revealed from an abnormal increase in autophagosomes and autolysosomes. This eventually results in autophagy-associated cancer cell death accompanied by the characteristics of apoptosis and ferroptosis. Overall, the present work paves a new way for cancer therapy via precise lysosome impairment induced autophagy dysfunction.

Longitudinal analyses of composite resin restoration on erosive lesions: effect of dentin treatment with a chitosan nanoformulation containing green tea

Aim To evaluate the influence of the biomodification of erosive lesions with a chitosan nanoformulation containing green tea (NanoCsQ) on the clinical performance of a composite resin. Methods The study was performed in a split-mouth, randomized and double-blinded model with 20 patients with 40 erosive lesions. The patient's teeth were randomized into two groups (n=20) according to the surface treatment: 1) Without biomodification (control), and 2) Biomodification with NanoCsQ solution (experimental). The lesions were restored with adhesive (Tetric N-bond, Ivoclar) and composite resin (IPS Empress Direct, Ivoclar). The restorations were polished and 7 days (baseline), 6 months, and 12 months later were evaluated according to the United States Public Health Service (USPHS) modified criteria, using clinical exam and photographics. Data were analyzed by Friedman's and Wilcoxon signed-rank tests. Results No significant differences were found between the control and experimental groups (p=0.423), and also among the follow-up periods (baseline, six months, and 12 months) (p=0.50). Regarding the retention criteria, 90% of the restoration had an alpha score in the control group. Only 10% of the restorations without biomodification (control) had a score charlie at the 12-month follow-up. None of the patients reported post-operatory sensitivity. Conclusion The NanoCsQ solution did not negatively affect the performance of the composite resin restorations after 12 months.

Carbon Dots Derived from Tea Polyphenols as Photosensitizers for Photodynamic Therapy.

Photodynamic therapy (PDT) has become an emerging cancer treatment method. Choosing the photosensitizer (PS) compounds is one of the essential factors that can influence the PDT effect and action. Carbon dots (CDs) have shown great potential as photosensitizers in PDT of cancers due to their excellent biocompatibility and high generation of reactive oxygen species (ROS). Here, we used tea polyphenol as raw material for synthesized tea polyphenol carbon dots (T-CDs) that show dual emission bands of red and blue fluorescence and can efficiently generate hydroxyl radicals (OH) under mildly visible irradiation with a LED light (400-500 nm, 15 mW cm-2). The extremely low cytotoxicity and excellent biocompatibility of T-CDs without light irradiation were tested using MTT and hemolytic assay. Further, T-CDs have been shown by in vivo experiments, using a mouse breast cancer cell line (4T1) subcutaneously injected in the back of the mouse buttock as a model, to effectively inhibit the tumor cell proliferation in solid tumors and show an excellent PDT effect. In addition, pathological sections of the mice tissues after further treatment showed that the T-CDs had no apparent impact on the major organs of the mice and did not produce any side effect lesions. This work demonstrates that the as-synthesized T-CDs has the potential to be used as a PS in cancer treatment.

Enhanced chemodynamic and photoluminescence efficiencies of Fe-O4 coordinated carbon dots via the core-shell synergistic effect.

In natural systems like photosynthetic organisms and photo-active enzymes, the spatial organization of chromophores is critical for efficient light harvesting and bio-catalysis. Inspired by nature, a novel modular nanoplatform with both biological imaging and therapeutic functions is constructed by taking advantage of the intrinsic core-shell structure of Fe-decorated carbon dots. Light-harvesting chromophores with deep-red photoluminescence are densely packed into the carbon core. Simultaneously, the atomically dispersed Fe3+ catalytic sites accounting for efficient conversion of H2O2 to ˙OH are discretely distributed on the shell. Precise control over their spatial distribution leads to the elegant integration and exciting interplay of the functional moieties. On the one hand, incorporating a catalysis shell enhances the emission of chromophores via synergistic shielding and rigidifying effects. On the other hand, visible light excitation of the chromophores significantly increases the catalytic activity and cytotoxicity against cancer cells, ascribed to the promotion of the charge transfer process. This nanoplatform exhibits excellent biocompatibility, bright red fluorescence, and light-regulated cytotoxicity for anti-cancer treatment, promising its applications in smart nanocatalytic medicines and efficient chemodynamic therapy.

Target selectivity of cholesterol-phosphatidylcholine liposome loaded with phthalocyanine for breast cancer diagnosis and treatment by photodynamic therapy.

This study investigated the ability of cholesterol-phosphatidylcholine liposomes loaded with chloride aluminum phthalocyanine (CL-AlClPc) to discriminate between healthy (MCF-10A) and neoplastic (MCF-7 and MDA-MB-231) breast cells for breast cancer diagnosis and treatment by photodynamic therapy (PDT) using a new drug delivery system consisting of CL-AlClPc. When PDT treatment was applied at an energy fluence of 700 mJ/cm², CL-AlClPc was more cytotoxic to neoplastic cells than to healthy breast cells because CL-AlClPc was better internalized by the tumor cells. An even higher fluorescence signal is expected for neoplastic cells during clinical treatment than for healthy cells, which will be useful for precise and targeted tumor cell detection. CL-AlClPc also facilitated better drug distribution and targeting of essential organelles inside the cells. This selectivity is critical for future in vivo diagnosis and treatment; it prevents side effects because it prioritizes tumor cells and tissues instead of healthy ones. The CL-AlClPc system designed herein had a small size (150 nm), low zeta potential (-6 mV), low polydispersity (0.16), high encapsulation rate efficiency (82.83%), and high shelf stability (12 months).

Melanoma spheroid-containing artificial dermis as an alternative approach to in vivo models.

Melanoma spheroid-loaded 3D skin models allow for the study of crucial tumor characteristics and factors at a superior level because the neoplastic cells are integrated into essential human skin components, permitting tumor-skin model communication. Herein, we designed a melanoma-containing artificial dermis by inserting multicellular tumor spheroids from the metastatic phase of WM 1617 melanoma cells into an artificial dermis. We cultured multicellular melanoma spheroids by hanging drop method (250 cells per drop) with a size of 420 µm in diameter after incubation for 14 days. These spheroids were integrated into the dermal equivalents that had been previously preparedwith a type-I collagen matrix and healthy fibroblasts. The melanoma spheroid cells invaded and proliferated in the artificial dermis. Spheroids treated with a 1.0 µmol/L aluminum chloride phthalocyanine nanoemulsion in the absence of light showed high cell viability. In contrast, under irradiation with visible red light (660 nm) at 25 J/cm2, melanoma cells were killed and the healthy tissue was preserved, indicating that photodynamic therapy is effective in such a model. Therefore, the 3D skin melanoma model has potential to promote research in full-thickness skin model targeting optimized preclinical assays.

Interaction of triblock copolymers (Pluronic®) with DMPC vesicles: a photophysical and computational study.

Pluronic/lipid mix promises stealth liposomes with long circulation time and long-term stability for pharmaceutical applications. However, the influence of Pluronics on several aspects of lipid membranes has not been fully elucidated. Herein it was described the effect of Pluronics on the structured water, alkyl chain conformation, and kinetic stability of dimyristoylphosphatidylcholine (DMPC) liposomes using interfacial and deeper fluorescent probes along with computational molecular modeling data. Interfacial water changed as a function of Pluronics' hydrophobicity with polypropylene oxide (PPO) anchoring the copolymers in the lipid bilayer. Pluronics with more than 30-40 PO units had facilitated penetration at the bilayer while shorter PPO favored a more interfacial interaction. Low Pluronic concentrations provided long-term stability of vesicles by steric effects of polyethylene oxide (PEO), but high amounts destabilized the vesicles as a sum of water-bridge cleavage at the polar head group and the reduced alkyl-alkyl interactions among the lipids. The high kinetic stability of Pluronic/DMPC vesicles is a proof-of-concept of its advantages and applicability in nanotechnology over conventional liposome-based pharmaceutical products for future biomedical applications.

F,N-Doped carbon dots as efficient Type I photosensitizers for photodynamic therapy.

Photodynamic therapy (PDT) is a promising and emerging method for the treatment of cancer. Usually, Type II PDT is used in the clinic, and mainly involves three key elements: a photosensitizer, molecular oxygen and laser light. However, it is known that tumor tissue is deficient in oxygen molecules which is why Type I PDT is mostly preferred in the therapy of tumors in which the hypoxic tissue plays a major role. Fluorescent carbon dots (CDs) have shown great potential in cancer theranostics, acting as bioimaging agents and photosensitizers. Herein, we have synthesized novel kinds of fluorine and nitrogen co-doped carbon dots (F,NCDs) that emit bright green fluorescence under ultra-violet light. The F,NCDs have excellent water solubility and low cytotoxicity. They can generate hydroxyl radicals (˙OH) and superoxide anions (˙O2-) under LED light (400-500 nm, 15 mW cm-2) irradiation, making them ideal photosensitizers for Type I PDT. Furthermore, upon using the HepG2 cell line as an in vitro model, the F,NCDs exhibit a better cell imaging effect and higher PDT efficiency than the control sample of CDs without F and N doping. This work has illustrated that the F,NCDs are promising in achieving the image-guided PDT of cancers, usually in a hypoxia tumor microenvironment.

Type-I Collagen/Collagenase Modulates the 3D Structure and Behavior of Glioblastoma Spheroid Models.

Multicellular tumor spheroids have emerged as well-structured, three-dimensional culture models that resemble and mimic the complexity of the dense and hypoxic cancer microenvironment. However, in brain tumor studies, a variety of glioblastoma multiforme (GBM) cell lines only self-assemble into loose cellular aggregates, lacking the properties of actual glioma tumors in humans. In this study, we used type-I collagen as an extracellular matrix component to promote the compaction of GBM aggregates forming tight spheroids to understand how collagen influences the properties of tumors, such as their growth, proliferation, and invasion, and collagenase to promote collagen degradation. The GBM cell lines U87MG, T98G, and A172, as well as the medulloblastoma cell line UW473, were used as standard cell lines that do not spontaneously self-assemble into spheroids, and GBM U251 was used as a self-assembling cell line. According to the findings, all cell lines formed tight spheroids at collagen concentrations higher than 15.0 µg mL-1. Collagen was distributed along the spheroid, similarly to that observed in invasive GBM tumors, and decreased cell migration with no effect on the cellular uptake of small active molecules, as demonstrated by uptake studies using the photosensitizer verteporfin. The enzymatic cleavage of collagen affected spheroid morphology and increased cell migration while maintaining cell viability. Such behaviors are relevant to the physiological models of GBM tumors and are useful for better understanding cell migration and the in vivo infiltration path, drug screening, and kinetics of progression of GBM tumors.

DNA polymer films used as drug delivery systems to early-stage diagnose and treatment of breast cancer using 3D tumor spheroids as a model.

The present study examines the design of DNA polymeric films (DNA-PFs) associated with aluminum chloride phthalocyanine (AlClPc) (DNA-PFs-AlClPc), as a promising drug delivery system (DDS), applicable for breast cancer treatment and early-stage diagnosis using photodynamic therapy (PDT). This study starts evaluating (MCF7) as a model for breast cancer cell behavior associated with DNA-PFs. Analyses of the morphological behaviors, biochemical reaction, and MCF7 cell adhesion profile on DNA-PFs were evaluated. SEM and AFM analysis allowed the morphological characterization of the DNA-PFs. Cell viability and cell cycle kinetics studies indicate highly biocompatible material capable of anchoring MCF7 cells, allowing the attachment and support of cell in the same structure where the insertion of AlClPc (DNA-PFs-AlClPc). The application of visible light photoactivation based on classical PDT protocol over the DNA-PFs-AlClPc showed a reduction in cell viability with increased cell death proportional to the fluency energy range from 600, 900, and 1800 mJ cm-2. The 3D organoid system mimics the tumor microenvironment which was precisely observed in human breast cancer in early-stage progression in the body. The results observed indicate that the viability was reduced by more than 80% in monolayer culture and around 50% in the 3D organoid cell culture at the highest energy fluency (1800 mJ cm-2). With low energy fluency (100 mJ cm-2,), the DNA-PFs-AlClPc did not show a cytotoxic effect on MCF7 cells, enabling the potential for photodiagnosis of early-stage human breast cancer detection in the initial stage of progression.

Photoinactivation of multispecies cariogenic biofilm mediated by aluminum phthalocyanine chloride encapsulated in chitosan nanoparticles.

This study aimed to characterize the aluminum phthalocyanine chloride (AlClPc) encapsulated in chitosan nanoparticles (CN) and apply it in antimicrobial photodynamic therapy (aPDT) on multispecies biofilm composed of Streptococcus mutans, Lactobacillus casei, and Candida albicans to analyze the antimicrobial activity and lactate production after treatment. Biofilms were formed in 24-well polystyrene plates at 37 °C for 48 h under microaerophilia. The following groups were evaluated (n = 9): as a positive control, 0.12% chlorhexidine gluconate (CHX); phosphate-buffered saline (PBS) as a negative control; 2.5% CN as release vehicle control; the dark toxicity control of the formulations used (AlClPc and AlClPc + CN) was verified in the absence of light; for aPDT, after 30 min incubation time, the photosensitizers at a final concentration of 5.8 × 10-3 mg/mL were photoirradiated for 1 min by visible light using a LED device (AlClPc + L and AlClPc + CN + L) with 660 nm at the energy density of 100 J/cm2. An in vitro kit was used to measure lactate. The biofilm composition and morphology were observed by scanning electron microscopy (SEM). The antimicrobial activity was analyzed by quantifying colony forming units per mL (CFU/mL) of each microorganism. Bacterial load between groups was analyzed by ANOVA and Tukey HSD tests (α = 0.05). A lower lactate dosage was observed in the aPDT AlClPc + CN + L and CHX groups compared to the CN and AlClPc groups. The aPDT mediated by the nanoconjugate AlClPc + CN + L showed a significant reduction in the viability of S. mutans (3.18 log10 CFU/mL), L. casei (4.91 log10 CFU/mL), and C. albicans (2.09 log10 CFU/mL) compared to the negative control PBS (p < 0.05). aPDT using isolated AlClPc was similar to PBS to the three microorganisms (p > 0.05). The aPDT mediated by the nanoconjugate AlClPc + CN + L was efficient against the biofilm of S. mutans, L. casei, and C. albicans.

Photosensitizer-based metal-organic frameworks for highly effective photodynamic therapy.

Photodynamic therapy (PDT) uses a photosensitizer, molecular oxygen, and visible light as an alternative clinical protocol against located malignant tumors and other diseases. More recently, PDT has been combined to immunotherapy as a promising option to treat metastatic cancer. However, previous generations of photosensitizers (PSs) revealed clinical difficulties such as long-term skin photosensitivity (first generation), the need for drug delivery vehicles (second generation), and intracellular self-aggregation (third generation), which have generated a somewhat confusing scenario in PDT approaches and evolution. Recently, metal-organic frameworks (MOFs) with exceptionally high PS loading as a building unit of MOF framework have emerged as fourth-generation PS and presented outstanding outcomes under pre-clinical studies. For PS-based MOFs, the inorganic building unit (metal ions/clusters) plays an important role as a coadjuvant in PDT to alleviate hypoxia, to decrease antioxidant species, to yield ROS, or to act as a contrast agent for imaging-guided therapy. In this review, we intend to carry out a broad update on the recent history and the characteristics of PS-based MOFs from basic chemistry to the structure relationship with biological application in PDT. The details and variables that result in different photophysics, size, and morphology, are discussed. Also, we present an overview of the achievements on the pre-clinical assays in combination with other strategies, including alleviating hypoxia in solid tumors, chemotherapy, and the most recent immunotherapy for cancer.

Synergistic effect of photobiomodulation and phthalocyanine photosensitizer on fibroblast signaling responses in an in vitro three-dimensional microenvironment.

Photobiomodulation (PBM) is a promising medical treatment modality in the area of photodynamic therapy (PDT). In this study, we investigated the effect of combined therapy in a 3D microenvironment using aluminum chloride phthalocyanines (AlClPc) as the photosensitizing agent. Normal human fibroblast-containing collagen biomatrix was prepared and treated with an oil-in-water (o/a) AlClPc-loaded nanoemulsion (from 0.5 to 3.0 µM) and irradiated at a range of fluences (from 0.1 to 3.0 J/cm2) using a continuous-wave light-emitting diode (LED) irradiation system (660 nm). PBM at 1.2 J/cm2 and AlClPc/NE at 0.5 µM modified the fibroblast signaling response under 3D conditions, promoting collagen synthesis, ROS production, MMP-9 secretion, proliferation of the actin network, and facile myofibroblastic differentiation. PBM alone (at 1.2 J/cm2 and 0.3 J/cm2) had no significant effect on any of these parameters. The combined therapy affected myofibroblastic differentiation, inflammatory response, and extracellular matrix pliability, and should thus be examined further in subsequent studies considering that no side effects of PBM have been reported. Even though significant progress has been made in the field of phototherapy in recent years, it is necessary to further elucidate the detailed mechanisms underlying its effects already shown in 2D conditions to increase the acceptance of this beneficial and non-invasive therapeutic approach.

Effects of photodynamic therapy mediated by emodin in cervical carcinoma cells.

Cervical cancer is a worldwide public health problem, and improved selective therapies and anticancer drugs are urgently needed. In recent years, emodin has attracted considerable attention due to its anti-inflammatory, antineoplastic, and proapoptotic effects. Furthermore, emodin may be used as a photosensitizing agent in photodynamic therapy. Interest in photodynamic therapy for cancer treatment has increased due to its efficiency in causing tumor cell death. This study aimed to analyze the effect of emodin combined with photodynamic therapy in cervical carcinoma cell lines. At first, emodin presented cytotoxicity in concentration and time-dependent manners in all the specific cell lines analyzed. SiHa, CaSki, and HaCaT cancer cells presented more than 80% cell viability in concentrations below 30 µmol/L. Fluorescence microscopy images showed efficient cellular uptake of emodin in all analyzed cell lines. A significant decrease in cell viability was observed in SiHa, CaSki, and HaCaT cell lines after treatment of emodin combined with photodynamic therapy. These decreases were accompanied by increased ROS production, caspase-3 activity, and fluorescence intensity of autophagic vacuoles. This suggests increased ROS production led to cell death by apoptosis and autophagy. Additionally, after the combination of emodin and photodynamic therapy in SiHa cells, we observed the overexpression of 22 target genes and downregulation of two target genes of anti-cancer drugs. These results show the promising potential for applications that combine emodin with photodynamic therapy for cervical cancer treatment.