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Photodynamic Antimicrobial Chemotherapy (PACT), using Toluidine blue (TBO) inhibits both growth and dimorphism in Paracoccidioides brasiliensis by a mechanism involving reactive Oxygen species (ROS) production
摘要： Background: The thermo-dimorphic fungus Paracoccidioides brasiliensis causes Paracoccidioidomycosis (PCM), an important public health problem in Latin American, with prevalence in Brazil [1-4]. One of the main problems of this mycosis, initially pulmonary, are the secondary mucosal lesions, which are debilitating, painful and, in some cases, generate mutilations [3,5-8]. The treatment is performed through the use of oral medicines anti-fungal and/or oral surgeries [3]. The Photodynamic Antimicrobial Chemotherapy (PACT) has been suggested as a promising alternative and/or complementary therapy against many pathogens [9-16] and has been little explored in the treatment of individuals with PCM [17-18]. Aims: The objective of this work was study the effect of Photodynamic Antimicrobial Chemotherapy using Toluidine blue as a photosensitizer on both yeast and mycelial cells of Paracoccidioides brasiliensis, isolated 18, and the possible mechanism involved on PACT action.
关键词： Toluidine Blue,Paracoccidioides brasiliensis,Photodynamic Antimicrobial Chemotherapy,dimorphism,fungus
更新于2025-09-23 15:22:29
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Extracellular vesicles based self-grown gold nanopopcorn for combinatorial chemo-photothermal therapy
摘要： Here, we generated a popcorn-like gold nanostructure exploiting extracellular vesicles (EVs). EVs can first serve as the vehicle for chemotherapeutic drug doxorubicin (DOX). Taking advantages of EVs, gold nanoparticles can be then self-grown surrounding the EVs, assembling into popcorn-like nanostructure. The formulated nanopopcorn, consisting of self-grown gold nanoparticles and EVs encapsulated with DOX, retained the photothermal transduction from gold nanoparticle assemblies and cytotoxicity of DOX. Under external near infrared irradiation, gold nanopopcorn can produce hyperthermia to induce tumor ablation and trigger drug release, achieving combinatorial chemo-photothermal therapy. The nanoplatform demonstrated improved cellular internalization, controlled drug release, enhanced antitumor efficacy with tumor inhibitory rate up to 98.6% and reduced side effects. Our design of popcorn-like nanostructure will contribute a novel modality for facile and green synthesis of complex metal nanostructures exploiting natural properties of EVs for combinational therapy.
关键词： photothermal therapy,self-growth,gold nanopopcorn,chemotherapy,extracellular vesicles
更新于2025-09-23 15:22:29
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Carbon Nanomaterials for Bioimaging, Bioanalysis, and Therapy || Functionalized Carbon Nanomaterials for Drug Delivery
摘要： Chemical functionalization of nanomaterials is important to control their physical properties. Since their applications frequently require the homogeneity in the physical properties of the components, many precise functionalization methods for nanomaterials have been developed in view of their applications from electronics and optics to biomedicine. Nanomedicine has been attracting growing interest in terms of therapy and diagnosis, or so called theranostics. In the field, nanomaterials play a key role and hence they are chemically functionalized frequently to meet the requirements for the purpose. In the nanomaterial‐based drug delivery system (DDS), for example, the following functions are required: the nanodrug has to disperse well in the blood to avoid embolism; circulate throughout the body to avoid leaking from the pores in the blood vessel and trapping in the reticuloendothelial system; accumulate in the targeting organ or tissue; and finally, release the loaded drug. Among the nanomaterials in the DDS, carbon nanomaterials have the following characteristic properties: (i) basically inert, but functionizable at the functional groups such as carboxylic and hydroxyl ones on the surface, edge, and defect through organic transformation; (ii) variety of options in terms of shapes including zero‐dimensional (0D, fullerenes), one‐dimensional (1D, carbon nanotubes, CNTs), two‐dimensional (2D, graphene, G), and three‐dimensional (3D, nanodiamond, ND); (iii) commercially available; and (iv) fluorescence emission from semiconducting SWNTs, relatively small size graphenes and color center in ND. The carbon nanomaterials discussed in this chapter are graphene (Section 10.2) and ND (Sections 10.3 and 10.4). Graphene has a flat and hydrophobic surface consisting of sp2 carbons. It exhibits high affinity to the flat molecules, including π‐electrons such as triphenylene, as we reported quite recently. Therefore, it has been utilized as carrier for anti‐cancer drugs with flat and hydrophobic properties. In addition, it can work as photosensitizer in photothermal therapy, making it more fascinating as a bifunctional material in cancer therapy. However, the graphene‐based carriers that have been used so far are graphene oxide (GO), because the carrier is required to have sufficient dispersibility in a physiological environment. The direct use of pristine graphene as a drug carrier, which will be described below, is the first example, as far as we know. On the other hand, ND has been reported to be low toxicity or even nontoxic nanomaterial. It is composed of the curved surface and core, not the flat surface and edge for graphene. As in the case of edge and defect in graphene, the ND surface is covered with various functional groups such as carboxylic and hydroxyl groups. Although ND is categorized as an inorganic nanomaterial due to its robustness and chemical stability, the surface functionalities impart the organic characteristics to ND, enabling the control of the physical property by controlling the surface functionality. Recently, surface chemical functionalization of ND has been actively investigated in view of its applications. In this chapter (Sections 10.3 and 10.4), chemical functionalization on ND for drug carrier will be described; the requisite functions of aqueous dispersibility, targeting specificity, and cytotoxicity are imparted to ND through stepwise surface chemical functionalization. This chapter covers synthesis, characterization, and evaluation of the following three nanodrugs: chlorin e6 (Ce6)‐loaded graphene for cancer phototherapy; Pt drug‐loaded nanodiamond for cancer chemotherapy; and DNA‐loaded nanodiamond for gene therapy.
关键词： nanodiamond,functionalization,drug delivery,graphene,phototherapy,chemotherapy,carbon nanomaterials,gene therapy
更新于2025-09-23 15:22:29
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Glutathione Triggered Near Infrared Fluorescence Imaging-guided Chemotherapy by Cyanine Conjugated Polypeptide
摘要： Precise detection of tumor environment for cancer diagnosis was strongly demanded for further therapies. Here, a redox-responsive fluorescence switch off/on system PCQ was designed and synthesized conjugated with near infrared (NIR) cyanine dyes (Cy5.5) and relevant quencher (FQ) in mixed polymeric micelles (PCy and PFQ). The mixed PCQ micelles was prepared with two kinds of polymer with poly (oligo (ethylene glycol) methacrylate) (POEGMA) as the hydrophilic shell, in which fluorescence emission was quenched by fluorescence resonance energy transfer (FRET) effect. The FQ was conjugated with POEGMA by disulfide linkage, which could be broke with redox environment such as high glutathione (GSH) concentration in tumor cells. After the PCQ micelles got into tumor cells, PFQ block in PCQ would be disassembled to recompose PCy micelles. During that process, drugs like doxorubicin (DOX) could be loaded inside and formed PCQ@DOX nanoparticles and then released for accurate NIR bioimaging and drug delivery instantly.
关键词： redox responsive,polypeptide,imaging-guided,chemotherapy,Near infrared fluorescence (NIRF)
更新于2025-09-23 15:21:21
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A high therapeutic efficacy of polymeric prodrug nano-assembly for a combination of photodynamic therapy and chemotherapy
摘要： Combination of photodynamic therapy and chemotherapy has been emerging as a new strategy for cancer treatment. Conventional photosensitizer tends to aggregate in aqueous media, which causes fluorescence quenching, reduces reactive oxygen species (ROS) production, and limits its clinical application to photodynamic therapy. Traditional nanoparticle drug delivery system for chemotherapy also has its disadvantages, such as low drug loading content, drug leakage, and off-target toxicity for normal tissues. Here, we developed a reduction-sensitive co-delivery micelles TB@PMP for combinational therapy, which composed of entrapping a red aggregation-induced emission fluorogen (AIEgen) for photodynamic therapy and PMP that contains a reduction-sensitive paclitaxel polymeric prodrug for chemotherapy. AIEgen photosensitizer illustrates a much improved photostability and ROS production efficiency in aggregate state and PMP loads a high dose of paclitaxel and carries a smart stimuli-triggered drug release property. This co-delivery system provides a better option that replaces AIEgen photosensitizer for cancer diagnosis and therapy.
关键词： chemotherapy,polymeric prodrug,cancer treatment,photodynamic therapy,nanoparticles
更新于2025-09-23 15:21:21
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Self-assembly of porphyrin-grafted lipid into nanoparticles encapsulating doxorubicin for synergistic chemo-photodynamic therapy and fluorescence imaging
摘要： The limited clinical efficacy of monotherapies in the clinic has urged the development of novel combination platforms. Taking advantage of light-triggered photodynamic treatment combined together with the controlled release of nanomedicine, it has been possible to treat cancer without eliciting any adverse effects. However, the challenges imposed by limited drug loading capacity and complex synthesis process of organic nanoparticles (NPs) have seriously impeded advances in chemo-photodynamic combination therapy. In this experiment, we utilize our previously synthesized porphyrin-grafted lipid (PGL) NPs to load highly effective chemotherapeutic drug, doxorubicin (DOX) for synergistic chemo-photodynamic therapy.
关键词： photodynamic therapy,doxorubicin,theranostics,chemotherapy,porphyrin
更新于2025-09-23 15:21:21
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Engineering Metal Organic Frameworks for Photoacoustic Imaging Guided Chemo/Photothermal Combinational Tumor Therapy
摘要： Imaging-guided therapy has considerable potential in tumor treatment. Different treatments have been integrated to realize combinational tumor therapy with improved therapeutic efficiency. Herein, the conventional metal organic framework (MOF) MIL-100 is utilized to load curcumin with excellent encapsulation capacity. Polydopamine-modified hyaluronic acid (HA-PDA) is coated on MIL-100 surface to construct engineering MOF nanoparticles (MCH NPs). The HA-PDA coating not only improves the dispersibility and stability of NPs but also introduces a tumor-targeting ability to this nanosystem. A two-stage augmented photothermal conversion capability is introduced to this nanosystem by encapsulating curcumin in MIL-100 pores and then coating HA-PDA on the surface, which confer the MCH NPs with strong photothermal conversional efficiency. After being intravenously injected into xenograft HeLa tumor-bearing mice, MCH NPs prefer to accumulate at the tumor site and achieve photoacoustic imaging-guided chemo/photothermal combinational tumor therapy, generating nearly complete tumor ablation. Engineering MOFs is an efficient platform for imaging-guided combinational tumor therapy, as confirmed by in vitro and in vivo evaluations.
关键词： curcumin,photoacoustic imaging,metal organic frameworks,chemotherapy,photothermal therapy
更新于2025-09-23 15:21:21
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PEGylated polyethylenimine-stabilized polypyrrole nanoparticles loaded with DOX for chemo-photothermal therapy of cancer cells
摘要： Combination of kinds of therapy modalities is promising for effective cancer treatment. Herein, a kind of multifunctional nanoparticles (NPs) was developed for cancer chemo-photothermal therapy applications. Polypyrrole (PPy) NPs were formed using a facile polymerization method using poly(ethyleneimine) (PEI) as stabilizer, followed by polyethylene glycol (PEG) modification and anticancer drug doxorubicin (DOX) loading. Showing obvious absorbance in the NIR range, the obtained PPy-PEI-PEG NPs displayed well photothermal ability with desirable photothermal stability. The release of the loaded DOX can be promoted by pH and laser stimulation. Compared with single therapy modality, the combination of chemotherapy and photothermal therapy showed higher cancer cell killing effect. The cellular internalization of the obtained NPs was proved to be effective. The developed multifunctional NPs are promising candidates for combined therapy of cancer cells.
关键词： Polypyrrole nanoparticles,Polyethylenimine,Nanomedicine,Photothermal therapy,Chemotherapy
更新于2025-09-23 15:21:21
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The near-infrared fluorescent dye IR-780 was coupled with cabazitaxel for castration-resistant prostate cancer imaging and therapy
摘要： A new drug, Caba-780, was synthesized by chemical coupling of the heptamethyl phthalocyanine near-infrared fluorescent (NIRF) dye IR-780 and the paclitaxel-based chemotherapeutic drug cabazitaxel. Then, the potential value of Caba-780 in the diagnosis and treatment of castration-resistant prostate cancer (CRPC) was evaluated. The CRPC cell lines DU145 and PC-3, as well as the normal human prostate stromal cell line WPMY-1, were used to evaluate the uptake of Caba-780 and its antitumor effect in vitro. The distribution, antitumor effect, and safety of Caba-780 were also evaluated in tumor-bearing mouse xenograft models. Our results showed that Caba-780 was efficiently absorbed by DU145 and PC-3 cells and that the cytotoxicity of Caba-780 was significantly stronger than that of IR-780 and cabazitaxel. In addition, Caba-780 inhibited the migration and invasion of DU145 and PC-3 cells and promoted apoptosis by prolonging the G2 phase of the cell cycle. Further analysis indicated that Caba-780 could be used to effectively image tumor xenografts. At the same time, this drug inhibited the growth of tumors in vivo. Therefore, the new synthetic drug Caba-780 has potential applications in the diagnosis and treatment of CRPC.
关键词： Organic anion-transporting polypeptide,Chemotherapy,Castration-resistant prostate cancer,Near-infrared fluorescent dye
更新于2025-09-23 15:21:01
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Partially Solvated Dinuclear Ruthenium Compounds Bridged by Quinoxaline-Functionalized Ligands as Ru(II) Photocage Architectures for Low-Energy Light Absorption
摘要： Ruthenium compounds with coordinated photo-labile molecules that can be selectively released by irradiation with a visible light source are finding increasing applications in photoactivated chemotherapy (PCT) as photocages. Earlier photocages based on mononuclear Ru(II) compounds lack absorption in the therapeutic window (λ > 600 nm). In previous work, we synthesized the first partially solvated tppz bridged (tppz= 2,3,5,6-tetrakis(pyridin-2-yl)pyrazine) dinuclear Ru(II) complex capable of photoinduced ligand exchange at both metal centers. To further explore the effect of the bridging ligand on Ru(II) photocage design, we used quinoxaline-functionalized bridging ligand platforms to prepare [{RuII(NCCH3)4}2(μ-BL)](PF6)4[BL = dpq, 2,3-di(pyridin-2-yl)quinoxaline (1); BL = dpb, 2,3-di(pyridin-2-yl)benzo[g]quinoxaline (2)]. The compounds are capable of absorbing green light with tails extending beyond 650 nm which can be exploited for applications as PCT agents. Experimental results were additionally verified by DFT calculations. The use of two Ru(II) centers equipped with quinoxaline-based bridging ligands is a promising design strategy for the synthesis of a new family of dinuclear Ru(II) photocage prototypes with the ability to absorb low-energy visible light.
关键词： photoactivated chemotherapy,Ruthenium compounds,photocages,low-energy light absorption,dinuclear Ru(II) complexes
更新于2025-09-23 15:19:57