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.

Chitosan nanoparticles loaded with epigallocatechin-3-gallate: synthesis, characterisation, and effects against Streptococcus mutans biofilmEpigallocatechin-loaded chitosan nanoparticles: effects against Streptococcus mutans biofilm.

This study evaluated the effects of chitosan nanoparticles loaded with epigallocatechin-3-gallate (EGCG) against Streptococcus mutans biofilm. EGCG-loaded chitosan (Nchi + EGCG) nanoparticles and Chitosan (Nchi) nanoparticles were prepared by ion gelation process and characterised regarding particle size, polydispersion index, zeta potential, and accelerated stability. S mutans biofilms were treated twice daily with NaCl 0.9% (negative control), Nchi, Nchi + EGCG, and chlorhexidine (CHX) 0.12% (positive control). After 67 h, the biofilms were evaluated for acidogenesis, bacterial viability and dry weight. Biofilm morphology and structure were analysed by scanning electron microscopy. The nanoformulations presented medium to short-term stability, size of 500 nm, and polydispersion index around 0.400. Treatments affected cell morphology and biofilm structure. However, no effects on microbial viability, biofilm dry weight, and acidogenesis were observed. Thus, the nanoformulations disassembled the biofilm matrix without affecting microbial viability, which makes them promising candidates for the development of dental caries preventive and therapeutic agents.

A standard procedure for rapid toxicity evaluation of carbon dots both in vitro and in vivo.

Carbon dots (CDs) are an emerging class of fluorescent quantum dot nanomaterials that have attracted considerable scientific attention for biomedical or bioimaging applications due to their physicochemical and biochemical properties. With the emergence of massive novel synthetic CDs applying to biomedical fields of science, evaluating their biosafety before any biological application is essential. However, there is no universal protocol or routine procedures for toxicity detection and biosafety assessment of CDs in general biological environments. Herein, we provide an ideal and fast operating system to detect the biotoxicity of CDs, which has been preliminary practiced. Briefly, the obtained CDs will be evaluated by in vitro cytotoxicity assay using cell counting kit-8, lactate dehydrogenase assay kit, and flow cytometry. Meanwhile, the model creature zebrafish is employed to perform in vivo evaluation by measuring body length, hatching rate, heart rate, and morphological observation. Our operating procedure condenses previous scattered biosafety detection methods into a rapid standard evaluation protocol that can be applied to early biotoxicity screening of CDs. This protocol will accelerate CDs biological exploitation and guide future industrialized biosafety assessment in large-scale applications.

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.

Photo-responsive polymeric micelles for the light-triggered release of curcumin targeting antimicrobial activity.

Nanocarriers have been successfully used to solubilize, deliver, and increase the bioavailability of curcumin (CUR), but slow CUR release rates hinder its use as a topical photosensitizer in antimicrobial photodynamic therapy. A photo-responsive polymer (PRP) was designed for the light-triggered release of CUR with an effective light activation-dependent antimicrobial response. The characterization of the PRP was compared with non-responsive micelles comprising Pluronics™ P123 and F127. According to the findings, the PRP formed photo-responsive micelles in the nanometric scale (< 100 nm) with a lower critical micelle concentration (3.74 × 10-4 M-1, 5.8 × 10-4 M-1, and 7.2 × 10-6 M-1 for PRP, F127, P123, respectively, at 25°C) and higher entrapment efficiency of CUR (88.7, 77.2, and 72.3% for PRP, F127, and P123 micelles, respectively) than the pluronics evaluated. The PRP provided enhanced protection of CUR compared to P123 micelles, as demonstrated in fluorescence quenching studies. The light-triggered release of CUR from PRP occurred with UV light irradiation (at 355 nm and 25 mW cm-2) and a cumulative release of 88.34% of CUR within 1 h compared to 80% from pluronics after 36 h. In vitro studies showed that CUR-loaded PRP was non-toxic to mammal cell, showed inactivation of the pathogenic microorganisms Candida albicans, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus, and decreased biofilm biomass when associated with blue light (455 nm, 33.84 J/cm2). The findings show that the CUR-loaded PRP micelle is a viable option for antimicrobial activity.

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.

In vitro antibacterial activity of green tea-loaded chitosan nanoparticles on caries-related microorganisms and dentin after Er:YAG laser caries removal.

This study aimed to determine the inhibitory effects of green tea (Gt), EGCG, and nanoformulations containing chitosan (Nchi) and chitosan+green tea (Nchi+Gt) against Streptococcus mutans and Lactobacillus casei. In addition, the antibacterial effect of nanoformulations was evaluated directly on dentin after the selective removal of carious lesion. At first, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against S. mutans and L. casei isolates were investigated. In parallel, dentin specimens were exposed to S. mutans to induce carious lesions. Soft dentin was selectively removed by Er:YAG laser (n=33) or bur (n=33). Remaining dentin was biomodified with Nchi (n=11) or Gt+Nchi (n=11). Control group (n=11) did not receive any treatment. Dentin scraps were collected at three time points. Microbiological analyses were conducted and evaluated by agar plate counts. Gt at 1:32 dilution inhibited S. mutans growth while 1:16 was efficient against L. casei. EGCG at 1:4 dilution completely inhibited S. mutans and L. casei growth. Independently of the association with Gt, Nchi completely inhibited S. mutans at 1:4 dilution. For L. casei, different concentrations of Nchi (1:32) and Nchi+Gt (1:8) were required to inhibit cell growth. After selective carious removal, viability of S. mutans decreased (p<0.001), without difference between bur and Er:YAG laser (p>0.05). Treatment with Nchi and Nchi+Gt did not influence the microbial load of S. mutans on dentin (p>0.05). Although variations in concentrations were noticed, all compounds showed antibacterial activity against S. mutans and L. casei. Both bur and Er:YAG laser have effectively removed soft dentin and reduced S. mutans counts. Nanoformulations did not promote any additional antibacterial effect in the remaining dentin.

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.

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.

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.

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.

Photodynamic Anti-Bacteria by Carbon Dots and Their Nano-Composites.

The misuse of many types of broad-spectrum antibiotics leads to increased antimicrobial resistance. As a result, the development of a novel antibacterial agent is essential. Photodynamic antimicrobial chemotherapy (PACT) is becoming more popular due to its advantages in eliminating drug-resistant strains and providing broad-spectrum antibacterial resistance. Carbon dots (CDs), zero-dimensional nanomaterials with diameters smaller than 10 nm, offer a green and cost-effective alternative to PACT photosensitizers. This article reviewed the synthesis methods of antibacterial CDs as well as the recent progress of CDs and their nanocomposites in photodynamic sterilization, focusing on maximizing the bactericidal impact of CDs photosensitizers. This review establishes the base for future CDs development in the PACT field.

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.

A Genetic Model of Epilepsy with a Partial Alzheimer's Disease-Like Phenotype and Central Insulin Resistance.

Studies have suggested an important connection between epilepsy and Alzheimer's disease (AD), mostly due to the high number of patients diagnosed with AD who develop epileptic seizures later on. However, this link is not well understood. Previous studies from our group have identified memory impairment and metabolic abnormalities in the Wistar audiogenic rat (WAR) strain, a genetic model of epilepsy. Our goal was to investigate AD behavioral and molecular alterations, including brain insulin resistance, in naïve (seizure-free) animals of the WAR strain. We used the Morris water maze (MWM) test to evaluate spatial learning and memory performance and hippocampal tissue to verify possible molecular and immunohistochemical alterations. WARs presented worse performance in the MWM test (p < 0.0001), higher levels of hyperphosphorylated tau (S396) (p < 0.0001) and phosphorylated glycogen synthase kinase 3 (S21/9) (p < 0.05), and lower insulin receptor levels (p < 0.05). Conversely, WARs and Wistar controls present progressive increase in amyloid fibrils (p < 0.0001) and low levels of soluble amyloid-ß. Interestingly, the detected alterations were age-dependent, reaching larger differences in aged than in young adult animals. In summary, the present study provides evidence of a partial AD-like phenotype, including altered regulation of insulin signaling, in a genetic model of epilepsy. Together, these data contribute to the understanding of the connection between epilepsy and AD as comorbidities. Moreover, since both tau hyperphosphorylation and altered insulin signaling have already been reported in epilepsy and AD, these two events should be considered as important components in the interconnection between epilepsy and AD pathogenesis and, therefore, potential therapeutic targets in this field.

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.