Near infrared photothermal inactivation of Candida albicans assisted by plasmonic nanorods.

The use of photothermal processes has been proven effective in the control of microbial infections. Simultaneously, the localized surface plasmon resonance phenomena in metallic nanoparticles have been explored as an alternative strategy to achieve highly efficient localized heating. In this work, we propose the use of selected nanoheaters to improve the efficiency of fungal photothermal inactivation of Candida albicans through size optimization of plasmonic gold nanorods. Here, the optical heating of polyethylene glycol coated gold nanorods of varying sizes is evaluated, both theoretically and experimentally. A size-dependent computational approach was applied to identify metallic nanorods with maximized thermal performance at 800 nm, followed by the experimental comparison of optimal and suboptimal nanoheaters. Comparison among samples show temperatures of up to 53.0 °C for 41×10 nm gold nanorods against 32.3 °C for 90×25 nm, a percentage increase of ∼63% in photothermal inactivation assessments. Our findings reveal that gold nanorods of 41×10 nm exhibit superior efficiency in near-infrared (800 nm) photothermal inactivation of fungi, owing to their higher light-thermal conversion efficiency. The identification of high performance metallic nanoheaters may lead to the reduction of the nanoparticle dose used in plasmonic-based procedures and decrease the laser exposure time needed to induce cell death. Moreover, our results provide insights to better exploit plasmonic nanoparticles on photothermal inactivation protocols.

Combinational photodynamic and photothermal - based therapies for melanoma in mouse models.

BACKGROUND: Melanoma is a highly metastatic skin cancer with limited response to current therapies in advanced patients. To overcome resistance, novel treatments based on photodynamic and photothermal therapies (PDT and PTT, respectively) have been developed to treat melanoma in preclinical murine models. Despite success inhibiting implanted tumors' growth, there has been limited evaluation of their long-term effectiveness in preventing metastasis, recurrence, or improving survival rates. METHODS: Combined and multidrug therapies based on PDT and/or PTT to treat cutaneous malignant melanoma in the preclinical mouse model were reviewed from 2016 onwards. PubMed® was the database in which the search was performed using mesh search algorithms resulting in fifty-one studies that comply with strict inclusion rules of screening. RESULTS: B16 melanoma-bearing C57BLACK6 mice model was the most used to evaluate immunotherapies, chemotherapies, and targeted therapies in combination with PDT and/or PTT. Combined therapies demonstrated a synergistic effect, resulting in intense antitumor activity. The most extensively studied protocol for developing metastatic models involved the intravenous administration of malignant cells, with some combined therapies being tested. Furthermore, the review presents the composition of the nanostructures utilized for delivering the drugs and light-responsive agents and the treatment plans for each combined approach. CONCLUSIONS: The identified mechanisms to simulate metastatic melanoma models and the therapeutic combinations may aid in evaluating the systemic protection of combined PDT and PTT-based therapies, particularly in conducting short-term preclinical experiments. Such simulations could have relevance to clinical studies.

Amphotericin-B-loaded polymer-functionalized reduced graphene oxides for Leishmania amazonensis chemo-photothermal therapy.

Two platforms based on reduced graphene oxide (rGO) functionalized with Pluronic® P123 (rGO-P123) and polyethyleneimine - PEI (rGO-PEI) polymers and loaded with amphotericin B (AmB) were fabricated and tested against Leishmania amazonensis, which can cause cutaneous and diffuse cutaneous leishmaniasis. The materials rGO-P123 and rGO-PEI were efficiently loaded with AmB - a polyene antibiotic - which resulted in rGO-P123-AmB (0.078 mg per mg of material) and rGO-PEI-AmB (0.086 mg per mg of material). Under near-infrared (NIR) light irradiation, the amount of AmB released from rGO-PEI-AmB at pH 5.0 and 7.4 doubled in comparison to AmB released in the absence of NIR light under identical conditions. It was accompanied by a photothermal effect. Otherwise, rGO-P123-AmB did not show a significant change in AmB released in the presence and absence of NIR light. Cytotoxicity studies in mammalian host macrophages revealed that rGO-PEI and rGO-PEI-AmB were nontoxic to the host cells, whereas rGO-123 and rGO-P123-AmB were very toxic, particularly the latter. Therefore, only rGO-PEI and rGO-PEI-AmB were tested against L. amazonensis promastigotes in the presence and absence of NIR light. In vitro antiproliferative effects revealed that rGO-PEI-AmB showed a more pronounced activity against the parasite than rGO-PEI, which was improved under NIR light irradiation. Scanning-transmission electron microscopy of L. amazonensis promastigotes after incubation with rGO-PEI or rGO-PEI-AmB suggested autophagic and necrotic cell death. Thus, the facile synthesis, high AmB loading capacity and good photothermal effect make the rGO-PEI-AmB platform a promising candidate for the topical treatment of cutaneous leishmaniasis.

Graphene Oxide Theranostic Effect: Conjugation of Photothermal and Photodynamic Therapies Based on an in vivo Demonstration.

INTRODUCTION: Cancer is the second leading cause of death globally and is responsible, where about 1 in 6 deaths in the world. Therefore, there is a need to develop effective antitumor agents that are targeted only to the specific site of the tumor to improve the efficiency of cancer diagnosis and treatment and, consequently, limit the unwanted systemic side effects currently obtained by the use of chemotherapeutic agents. In this context, due to its unique physical and chemical properties of graphene oxide (GO), it has attracted interest in biomedicine for cancer therapy. METHODS: In this study, we report the in vivo application of nanocomposites based on Graphene Oxide (nc-GO) with surface modified with PEG-folic acid, Rhodamine B and Indocyanine Green. In addition to displaying red fluorescence spectra Rhodamine B as the fluorescent label), in vivo experiments were performed using nc-GO to apply Photodynamic Therapy (PDT) and Photothermal Therapy (PTT) in the treatment of Ehrlich tumors in mice using NIR light (808 nm 1.8 W/cm2). RESULTS: This study based on fluorescence images was performed in the tumor in order to obtain the highest concentration of nc-GO in the tumor as a function of time (time after intraperitoneal injection). The time obtained was used for the efficient treatment of the tumor by PDT/PTT. DISCUSSION: The current study shows an example of successful using nc-GO nanocomposites as a theranostic nanomedicine to perform simultaneously in vivo fluorescence diagnostic as well as combined PDT-PTT effects for cancer treatments.

Photothermal therapy with silver nanoplates in HeLa cells studied by in situ fluorescence microscopy.

Photothermal therapy (PTT) is a noninvasive treatment for cancer relying on the incorporation of NIR-light absorbing nanomaterials into cells, which upon illumination release heat causing thermally induced cell death. We prove that irradiation of aqueous suspensions of poly(vinylpyrrolidone)-coated silver nanoplates (PVPAgNP) or PVPAgNP in HeLa cells with red or NIR lasers causes a sizeable photothermal effect, which in cells can be visualized with the temperature sensing fluorophore Rhodamine B (RhB) using spinning disk confocal fluorescence microscopy or fluorescence lifetime imaging. Upon red-light irradiation of cells that were incubated with both, RhB and PVPAgNP at concentrations with no adverse effects on cell viability, a substantial heat release is detected. Initiation of cell death by photothermal effect is observed by positive signals of fluorescent markers for early and late apoptosis. Surprisingly, a new nanomaterial-assisted cell killing mode is operating when PVPAgNP-loaded HeLa cells are excited with moderate powers of fs-pulsed NIR light. Small roundish areas are generated with bright and fast (<1 ns) decaying emission, which expand fast and destroy the whole cell in seconds. This characteristic emission is assigned to efficient optical breakdown initiation around the strongly absorbing PVPAgNP leading to plasma formation that spreads fast through the cell.

Carbon-Based Materials in Photodynamic and Photothermal Therapies Applied to Tumor Destruction.

Within phototherapy, a grand challenge in clinical cancer treatments is to develop a simple, cost-effective, and biocompatible approach to treat this disease using ultra-low doses of light. Carbon-based materials (CBM), such as graphene oxide (GO), reduced GO (r-GO), graphene quantum dots (GQDs), and carbon dots (C-DOTs), are rapidly emerging as a new class of therapeutic materials against cancer. This review summarizes the progress made in recent years regarding the applications of CBM in photodynamic (PDT) and photothermal (PTT) therapies for tumor destruction. The current understanding of the performance of modified CBM, hybrids and composites, is also addressed. This approach seeks to achieve an enhanced antitumor action by improving and modulating the properties of CBM to treat various types of cancer. Metal oxides, organic molecules, biopolymers, therapeutic drugs, among others, have been combined with CBM to treat cancer by PDT, PTT, or synergistic therapies.

Gold nanoparticle-mediated generation of reactive oxygen species during plasmonic photothermal therapy: a comparative study for different particle sizes, shapes, and surface conjugations.

Gold nanoparticle (AuNP)-mediated photothermal therapy represents an alternative to the effective ablation of cancer cells. However, the photothermal response of AuNPs must be tailored to improve the therapeutic efficacy of plasmonic photothermal therapy (PPT) and mitigate its side effects. This study presents an alternative to ease the tuning of photothermal efficiency and target selectivity. We use laser-treated spherical and anisotropic AuNPs of different sizes and biocompatible folic acid (FA)-conjugated AuNPs (FA-AuNPs) in the well-known human epithelial cervical cancer (HeLa) cell line. We show that large AuNPs produce a more significant photothermal heating effect than small ones. The thermal response of the spherical AuNPs of 9 nm was found to reach a maximum increase of 3.0 ± 1 °C, whereas with the spherical AuNPs of 14 nm, the temperature increased by over 4.4 ± 1 °C. The anisotropic AuNPs of 15 nm reached a maximum of 4.0 ± 1 °C, whereas the anisotropic AuNPs of 20 nm reached a significant increase of 5.3 ± 1 °C in the cell culture medium (MEM). Notably, the anisotropic AuNPs of 20 nm successfully demonstrate the potential for use as a photothermal agent by showing reduced viability down to 60% at a concentration of 100 µM. Besides, we reveal that high concentrations of reactive oxygen species (ROS) are formed within the irradiated cells. In combination with stress by photothermal heating, it is likely to result in significant cell death through acute necrosis by compromising the plasma membrane integrity. Cell death and ROS overproduction during PPT were characterized and quantified by transmission electron microscopy (TEM) and confocal fluorescence microscopy with different fluorescent markers. In addition, we show that FA-AuNPs induce cell death through apoptosis by internal damage, whereas diminish the ROS formation during PPT treatment. Our findings suggest the ability of plasmon-mediated ROS to sensitize cancer cells and make them vulnerable to photothermal damage, as well as the protective role of FA-AuNPs from excessive ROS formation, whereas reducing the risk of undesired side effects due to the necrotic death pathway. It allows an improvement in the efficacy of the AuNP-based photothermal therapy and a reduction in the number of exposures to high temperatures required to induce thermal stress.

Predictive Model for Delivery Efficiency: Erythrocyte Membrane-Camouflaged Magnetofluorescent Nanocarriers Study.

Delivery efficiencies of theranostic nanoparticles (NPs) based on passive tumor targeting strongly depend either on their blood circulation time or on appropriate modulations of the tumor microenvironment. Therefore, predicting the NP delivery efficiency before and after a tumor microenvironment modulation is highly desirable. Here, we present a new erythrocyte membrane-camouflaged magnetofluorescent nanocarrier (MMFn) with long blood circulation time (92 h) and high delivery efficiency (10% ID for Ehrlich murine tumor model). MMFns owe their magnetic and fluorescent properties to the incorporation of manganese ferrite nanoparticles (MnFe2O4 NPs) and IR-780 (a lipophilic indocyanine fluorescent dye), respectively, to their erythrocyte membrane-derived camouflage. MMFn composition, morphology, and size, as well as optical absorption, zeta potential, and fluorescent, magnetic, and magnetothermal properties, are thoroughly examined in vitro. We then present an analytical pharmacokinetic (PK) model capable of predicting the delivery efficiency (DE) and the time of peak tumor uptake (tmax), as well as changes in DE and tmax due to modulations of the tumor microenvironment, for potentially any nanocarrier. Experimental PK data sets (blood and tumor amounts of MMFns) are simultaneously fit to the model equations using the PK modeling software Monolix. We then validate our model analytical solutions with the numerical solutions provided by Monolix. We also demonstrate how our a priori nonmechanistic model for passive targeting relates to a previously reported mechanistic model for active targeting. All in vivo PK studies, as well as in vivo and ex vivo biodistribution studies, were conducted using two noninvasive techniques, namely, fluorescence molecular tomography (FMT) and alternating current biosusceptometry (ACB). Finally, histopathology corroborates our PK and biodistribution results.

Effective control of biofilms by photothermal therapy using a gold nanorod hydrogel.

Biofilms are matrices synthesized by bacteria containing polysaccharides, DNA, and proteins. The development of biofilms in infectious processes can induce a chronic inflammatory response that may progress to the destruction of tissues. The treatment of biofilms is difficult because they serve as a bacterial mechanism of defense and high doses of antibiotics are necessary to treat these infections with limited positive results. It has been demonstrated that photothermal therapy using gold nanorods (AuNRs) is an attractive treatment because of its anti-biofilm activity. The purpose of this work was to generate a novel chitosan-based hydrogel embedded with AuNRs to evaluate its anti-biofilm activity. AuNRs were synthesized by the seed-mediated growth method and mixed with the chitosan-based hydrogel. Hydrogels were characterized and tested against two bacterial strains by irradiating the produced biofilm in the presence of the nanoformulation with a laser adjusted at the near infrared spectrum. In addition, the safety of the nanoformulation was assessed with normal human gingival fibroblasts. Results showed that a significant bacterial killing was measured when biofilms were exposed to an increase of 10°C for a short time of 2 min. Moreover, no cytotoxicity was measured when normal gingival fibroblasts were exposed to the nanoformulation using the bactericidal conditions. The development of the reported formulation can be used as a direct application to treat periodontal diseases or biofilm-produced bacteria that colonize the oral cavity.