High Therapeutic Efficiency Research Articles

First Results of Clinical Application of Ultraviolet Corneal Collagen Crosslinking in the Treatment of Corneal and Graft Ulcers in Children

Ulcerative lesions of the cornea and graft in children are a serious problem in pediatric ophthalmology, leading to serious consequences, up to the anatomical death of the eye. The problem of effective treatment of this pathology and corneal tissue regeneration in children remains relevant, despite the large arsenal of drugs. Recently, ultraviolet (UVA) corneal collagen crosslinking has been proposed as an alternative treatment for corneal ulcers in adults. RASK-CXL is the official name used exclusively for crosslinking in cornea inflammatory diseases. In children, corneal collagen crosslinking is still used only for the treatment of keratoconus. We were the first to use this method to treat corneal ulcers and graft ulcers in children.Purpose: to analyze the results of treatment of ulcerative corneal lesions and graft in children using a new device for local UVA crosslinking.Material and methods. For dynamic observation of patients, biomicroscopy with a fluorescein test, photo registration and optical coherence tomography of the eye anterior part were used. The procedure of local UVA crosslinking for the treatment cornea ulcerative lesions was carried out using a new device on the basis of the permission of the Ethics Committee of the National Medical Reseach Center of eye deseases named after Helmholtz of the Ministry of Health of Russia (protocol No. 56 of 21.10.2021).Results. The use of 3–5 procedures of local UVA exposure (against the background of instillations of 0.1 % riboflavin solution) lasting 5–7 minutes with an interval of 1-3 days ensured epithelization of the cornea and the graft and increased visual acuity in children.Conclusion. The first treatment results of corneal ulcers and graft in children using a new portable device for local UVA crosslinking have shown its high therapeutic efficiency and prospects for further use in clinical practice.

An Acellular Scaffold Facilitates Endometrial Regeneration and Fertility Restoration via Recruiting Endogenous Mesenchymal Stem Cells.

Severe intrauterine adhesions (IUAs), characterized by inadequate endometrial repair and fibrosis, can lead to infertility. Stem cell-based therapies, which deliver mesenchymal stem cells (MSCs) to the wound site, hold a considerable promise for endometrium regeneration. However, some notable hurdles, such as stemness loss, immunogenicity, low retention and survival rate, limit their clinical application. Evidence shows a strategy of mobilizing endogenous MSCs recruitment can overcome the traditional limitations of exogenous stem cell-based therapies. Here, an acellular biomaterial named stromal derived factor-1 alpha (SDF-1α)/E7-modified collagen scaffold (CES) is explored. CES based on harnessing the innate regenerative potential of the body enables near-complete endometrium regeneration and fertility restoration both in a rat endometrium acute damage model and a rat IUA model. Mechanistically, the CES implantation promotes endogenous MSCs recruitment via a macrophage-coordinated strategy; then the homing MSCs exert the function of immunomodulation and altered local microenvironments toward regeneration. To conclude, CES, which can harness endogenous MSCs and overcome the traditional limitations of cell-based therapies, can serve as a clinically feasible and cell-free strategy with high therapeutic efficiency for IUA treatment.

Analytical studies of scientific publications of the Pharmaceutical journal for 1959–2022 regarding the development of the composition and technology of medicinal products for the treatment of the wound process

An actual direction of scientific research is the problem of diagnosis and treatment of infected wounds. An important place in the general structure of diseases of general surgical profile is occupied by patients with purulent-inflammatory diseases of soft tissues, the frequency of which sometimes reaches indicators of 35–40%.
 With the development of medical science, ideas about wounds and methods of influencing the purulent-inflammatory process are constantly changing. Based on clinical criteria, three consecutive stages (phases) of the development of the wound process with different pathogenesis can be distinguished: purulent-necrotic (inflammatory) - characterized by the presence of necrotic tissues and purulent content in the wound; stage of granulation (regenerative) – manifested by cleaning the wound from purulent-necrotic sequestration and the formation of granulation tissue in it, which gradually fills the wound cavity; stage of epithelization (healing) – epithelization of the wound surface and formation of a scar.
 The purpose of the work was the analysis of scientific publications of the Pharmaceutical Journal on the development of the composition and technology of drugs for the treatment of the wound process for 1959–2022.
 The research materials were scientific publications of the scientific and practical edition of the Pharmaceutical Journal for the past 63 years (1959–2022), which used the methods of systematic and structural-logical analysis.
 The analysis of the scientific publications of the Pharmaceutical Journal over the past 63 years showed that soft drugs for local use do not lose their relevance for a long time. The appearance of new auxiliary substances, scientific knowledge of the wound process creates the basis for the development of new soft drugs and forms for the treatment of the wound process. The following factors are becoming relevant in drug technology: the basis for soft drugs, the correspondence of the phase of the wound process to soft drugs. The medical and biological requirements for the development of soft drugs are also evolving.
 The analysis of literature data showed that the use of multicomponent ointments on hydrophilic and emulsion bases, which have dehydrating and wound-healing effects, is technologically justified for the local treatment of the wound process.
 Soft drugs have a leading role in the local treatment of purulent wounds, as they ensure the achievement of the optimal concentration of active pharmaceutical ingredients in the affected area, ensuring high therapeutic efficiency and prolonged effect. Natural components that are part of wound-healing ointments have a significant breadth of pharmacological action, low toxicity and rarely cause side reactions, unlike synthetic agents.

Multivalent cyclic template-directed synthesis of polycyclodextrin-based nanocarriers for enhanced chemotherapy

Nanocarriers with reversibly crosslinked structures provide one solution to the in vivo stability versus high therapeutic efficiency dilemma, however, generally suffer from a diluted condition-required synthetic approach for crosslinking. To address this issue, we reported herein multivalent cyclic template-directed synthesis of polycyclodextrin (polyCD)-based nanocarriers. The adopted multivalent cyclic template with great stability and steric hindrance resulted in a relatively high preparation concentration of 1.0 mg/mL for crosslinking. The synthesized dual-redox responsive polyCD-based crosslinked micelles showed enhanced colloidal stability, a high drug loading content (DLC) of 17.8% for doxorubicin (DOX), and intracellular complete destruction for promoted DOX release with enhanced anticancer efficiency in vivo. This study therefore not only reported the use of a multivalent cyclic polymer as a novel template for the production of polyCDs-based crosslinked micelles and ring-like colloids at a relatively high concentration, but also demonstrated great potential of the developed (polyCD)-based nanocarriers for enhanced chemotherapy.

Combined Photothermal and Photodynamic Therapy for Cancer Treatment Using a Multifunctional Graphene Oxide.

Graphene oxide (GO) is one of the most studied nanomaterials in many fields, including the biomedical field. Most of the nanomaterials developed for drug delivery and phototherapies are based on noncovalent approaches that lead to an unspecific release of physisorbed molecules in complex biological environments. Therefore, preparing covalently functionalized GO using straightforward and versatile methods is highly valuable. Phototherapies, including photothermal therapy (PTT) and photodynamic therapy (PDT), have shown great potential as effective therapeutic approaches against cancer. To overcome the limits of a single method, the combination of PTT and PDT can lead to a combined effect with a higher therapeutic efficiency. In this work, we prepare a folic acid (FA) and chlorin e6 (Ce6) double-functionalized GO for combined targeted PTT/PDT. This conjugate can penetrate rapidly into cancer cells and macrophages. A combined effect of PTT and PDT is observed, leading to a higher killing efficiency toward different types of cells involved in cancer and other diseases. Our work provides a simple protocol to prepare multifunctional platforms for the treatment of various diseases.

Inhaled amifostine for the prevention of radiation-induced lung injury

ObjectiveTo alleviate radiation-induced lung injury and prevent the related pneumonitis and pulmonary fibrosis by inhaled amifostine (AMI). Methods15 ​Gy 60Co γ-ray irradiation was performed on the thoracic area of rats once to establish the radiation injury model. AMI was intraperitoneally (i.p.) injected or intratracheally (i.t.) administered to the rats 30 ​min pre-irradiation. The protective effects of the two AMI administration manners were compared in the aspects of hematopoietic system, lung edema, and histopathological examination, and the mechanisms were explored. ResultsCompared to i.p. AMI, i.t. AMI remarkably alleviated radiation-induced lung injury and prevented consequent pneumonitis or pulmonary fibrosis. Specifically, i.t. AMI notably protected white blood cells and platelets, reduced the lung wet/dry weight ratio, and decreased collagen volume fractions compared to the model group (P ​< ​0.05), while i.p. AMI showed no significant difference with the model group (P ​> ​0.05). The high therapeutic efficiency of i.t. AMI was related to its high antioxidation and anti-inflammation effects with downregulation of pro-inflammatory cytokines, the enhanced superoxide dismutase activity, the low levels of malondialdehyde and total proteins. ConclusionInhaled AMI is a promising medicine for preventing radiation-induced lung injury, including pneumonitis and pulmonary fibrosis.

Dual Stimuli-Responsive Multifunctional Silicon Nanocarriers for Specifically Targeting Mitochondria in Human Cancer Cells.

Specific targeting, selective stimuli-responsiveness, and controlled release of anticancer agents are requested for high therapeutic efficiency with a minimal adverse effect. Herein, we report the sophisticated synthesis and functionalization of fluorescent mesoporous silicon (FMPSi) nanoparticles decorated with graphene oxide (GO) nanosheets. GO-wrapped FMPSi (FMPSi@GO) was loaded with a cisplatin (Cis) anticancer agent, and Cis-loaded FMPSi@GO (FMPSi-Cis@GO) exhibited the dual stimuli (pH and NIR)-responsiveness of controlled drug release, i.e., the drug release rate was distinctly enhanced at acidic pH 5.5 than at neutral pH 7.0 and further enhanced under NIR irradiation at acidic pH condition. Notably, dequalinium-conjugated FMPSi-Cis@GO (FMPSi-Cis@GO@DQA) demonstrated an excellent specificity for mitochondrial targeting in cancer cells without noticeable toxicity to normal human cells. Our novel silicon nanocarriers demonstrated not only stimuli (pH and NIR)-responsive controlled drug release, but also selective accumulation in the mitochondria of cancer cells and destroying them.

Single‐Cell Quantification of a Highly Biocompatible Dinuclear Iridium(III) Complex for Photocatalytic Cancer Therapy

AbstractQuantifying the content of metal‐based anticancer drugs within single cancer cells remains a challenge. Here, we used single‐cell inductively coupled plasma mass spectrometry to study the uptake and retention of mononuclear (Ir1) and dinuclear (Ir2) IrIII photoredox catalysts. This method allowed rapid and precise quantification of the drug in individual cancer cells. Importantly, Ir2 showed a significant synergism but not an additive effect for NAD(P)H photocatalytic oxidation. The lysosome‐targeting Ir2 showed low dark toxicity in vitro and in vivo. Ir2 exhibited high photocatalytic therapeutic efficiency at 525 nm with an excellent photo‐index in vitro and in tumor‐bearing mice model. Interestingly, the photocatalytic anticancer profile of the dinuclear Ir2 was much better than the mononuclear Ir1, indicating for the first time that dinuclear metal‐based photocatalysts can be applied for photocatalytic anticancer treatment.

Single-Cell Quantification of a Highly Biocompatible Dinuclear Iridium(III) Complex for Photocatalytic Cancer Therapy.

Quantifying the content of metal-based anticancer drugs within single cancer cells remains a challenge. Here, we used single-cell inductively coupled plasma mass spectrometry to study the uptake and retention of mononuclear (Ir1) and dinuclear (Ir2) IrIII photoredox catalysts. This method allowed rapid and precise quantification of the drug in individual cancer cells. Importantly, Ir2 showed a significant synergism but not an additive effect for NAD(P)H photocatalytic oxidation. The lysosome-targeting Ir2 showed low dark toxicity in vitro and in vivo. Ir2 exhibited high photocatalytic therapeutic efficiency at 525 nm with an excellent photo-index in vitro and in tumor-bearing mice model. Interestingly, the photocatalytic anticancer profile of the dinuclear Ir2 was much better than the mononuclear Ir1, indicating for the first time that dinuclear metal-based photocatalysts can be applied for photocatalytic anticancer treatment.

Acidity-responsive nanocages as robust reactive oxygen species generators with butterfly effects for maximizing oxidative damage and enhancing cancer therapy

Recently, with the rational design of transition metal-containing nanoagents, chemodynamic therapy (CDT) has been developed and considered a promising method for cancer therapy through Fenton and Fenton-like reaction-induced hydroxyl radical (·OH) generation and cellular oxidative damage. However, it is still a great challenge to realize high reactive oxygen species (ROS) generation and therapeutic efficiency under the strict conditions of the tumor microenvironment (TME). Herein, we design and fabricate a TME-responsive core-shell nanocage composed of a CaCO3 nanolayer and a heterogeneous CoP core (CaCO3@CoP, CCP) with the synergy of CDT and calcium overload to maximize oxidative damage and enhance cancer therapy. The CaCO3 nanoshell is sensitive to pH and can be rapidly degraded upon endocytosis, leading to intracellular Ca2+ accumulation, which further triggers the production of mitochondrial ROS. Subsequently, the CoP hollow nanocage with fully exposed Co active sites has high Fenton-like reactive activity to produce ·OH and induce mitochondrial damage. Mitochondrial damage and ROS elevation, in turn, can modulate Ca2+ dynamics and augment calcium overload. The reciprocal interaction and loop feedback between calcium overload and photoenhanced ROS generation via photothermal therapy (PTT) can further trigger the immunogenic cell death (ICD) process to activate the maturation of dendritic cells (DCs), activation of cytotoxic and helper T cells, and excretion of proinflammatory cytokines to enhance antitumor immunity in vivo. With the butterfly effect, CCP finally brings forth a greatly enhanced cancer therapeutic outcome in murine models.

Concentrically Encapsulated Dual-Enzyme Capsules for Synergistic Metabolic Disorder Redressing and Cytotoxic Intermediates Scavenging.

Enzyme therapy has important implications for the treatment of metabolic disorders and biological detoxification. It remains challenging to prepare enzymatic nanoreactors with high therapeutic efficiency and low emission of cytotoxic reaction intermediates. Here, we propose a novel strategy for the preparation of enzymes-loaded polypeptide microcapsules (EPM) with concentrically encapsulated enzymes to achieve higher cascade reaction rates and minimal emission of cytotoxic intermediates. Mesoporous silica spheres (MSS) are used as a highly porous matrix to efficiently load a therapeutic enzyme (glucose oxidase, GOx), and a layer-by-layer (LbL) assembly strategy is employed to assemble the scavenging enzyme (catalase) and polyelectrolyte multilayers on the MSS surface. After removal of the MSS, a concentrically encapsulated EPM is obtained with the therapeutic enzyme encapsulated inside the capsule, and the scavenging enzyme immobilized in the polypeptide multilayer shell. Performance of the concentrically encapsulated GOx-catalase capsules is investigated for synergistic glucose metabolism disturbance correction and cytotoxic intermediate H2O2 clearance. The results show that the EPM can simultaneously achieve 99% H2O2 clearance and doubled glucose consumption rate. This strategy can be extended to the preparation of other dual- or multi-enzyme therapeutic nanoreactors, showing great promise in the treatment of metabolic disorders.

Investigation of Anticancer Effects of Apigenin on MOLT-3 Human Leukaemia Cell Line

Leukaemia is an aggressive blood malignancies characterized by abnormal accumulation and proliferation of WBCs. Among children younger than 15 years, leukaemia consider the most common type of cancer which accounting 30% of all diagnosed malignancies. The Saudi Cancer Registry (SCR) reported that leukaemia ranked as the 5th type of cancer among both male and female. Because of the undesirable side-effects of the chemotherapy commonly used for leukaemia treatment such as high toxicity and development of secondary cancer, the search for novel and new promising treatment with fewer side-effects and higher therapeutic efficiency is still a priority goal. Using bioactive compounds from natural sources was an effective treatment for a variety of blood cancer. Thus, the aim of this study was to use the bioactive compound Apigenin to treat human lymphoid leukaemia cell line MOLT-3 with three different doses (25, 50, 100 µM) for 24 h. The results of this study showed that cellular proliferation was significantly reduced with 25, 50 and 100 µM Apigenin. In addition, significant increase in apoptotic induction was demonstrated when assessed with Annexin V-FITC/ PI and Caspase-3 substrate based on flow cytometry. Cell cycle arrest was significantly reported at S phase within MOLT-3 cells in a dose response manner. Thus, the finding of this study suggested that Apigenin is a potent and efficient anticancer compound through its activity of blocked cell proliferation, apoptotic induction and cell cycle arrest. However, further studies are required to investigate if the dietary intake of Apigenin might interfere with chemotherapeutic treatment of leukaemia.

Microbial hydrogen economy alleviates colitis by reprogramming colonocyte metabolism and reinforcing intestinal barrier

ABSTRACT With the rapid development and high therapeutic efficiency and biosafety of gas-involving theranostics, hydrogen medicine has been particularly outstanding because hydrogen gas (H2), a microbial-derived gas, has potent anti-oxidative, anti-apoptotic, and anti-inflammatory activities in many disease models. Studies have suggested that H2-enriched saline/water alleviates colitis in murine models; however, the underlying mechanism remains poorly understood. Despite evidence demonstrating the importance of the microbial hydrogen economy, which reflects the balance between H2-producing (hydrogenogenic) and H2-utilizing (hydrogenotrophic) microbes in maintaining colonic mucosal ecosystems, minimal efforts have been exerted to manipulate relevant H2–microbe interactions for colonic health. Consistent with previous studies, we found that administration of hydrogen-rich saline (HS) ameliorated dextran sulfate sodium–induced acute colitis in a mouse model. Furthermore, we demonstrated that HS administration can increase the abundance of intestinal-specific short-chain fatty acid (SCFA)–producing bacteria and SCFA production, thereby activating the intracellular butyrate sensor peroxisome proliferator–activated receptor γ signaling and decreasing the epithelial expression of Nos2, consequently promoting the recovery of the colonic anaerobic environment. Our results also indicated that HS administration ameliorated disrupted intestinal barrier functions by modulating specific mucosa-associated mucolytic bacteria, leading to substantial inhibition of opportunistic pathogenic Escherichia coli expansion as well as a significant increase in the expression of interepithelial tight junction proteins and a decrease in intestinal barrier permeability in mice with colitis. Exogenous H2 reprograms colonocyte metabolism by regulating the H2–gut microbiota–SCFAs axis and strengthens the intestinal barrier by modulating specific mucosa-associated mucolytic bacteria, wherein improved microbial hydrogen economy alleviates colitis.

A platinum-ruthenium hybrid prodrug with multi-enzymatic activities for chemo-catalytic therapy of hypoxic tumors.

Regulation of tumor hypoxia and redox homeostasis is a promising strategy for cancer therapy. Nanocatalytic medicine has played more and more important roles in this field because it can cleverly convert the efficiency and selectivity of catalysis into high therapeutic efficiency. Herein, we developed a platinum(iv)-ruthenium hybrid prodrug, named as Pt-Ru, for efficient chemo-catalytic synergistic therapy of hypoxic tumors. The ruthenium hybridization endowed the Pt(iv) prodrug with multi-enzyme catalytic activity, that is, mimicking catalase (CAT) to generate O2 in situ, mimicking peroxidase (POD) to produce reactive oxygen species, and mimicking glutathione peroxidase (GPx) to deplete GSH, thus effectively overcoming tumor hypoxia and cisplatin resistance. As a result, Pt-Ru treatment led to a superior anticancer efficacy to cisplatin both in vitro and in vivo. This work suggested redox homeostasis regulation as a tantalizing angle for developing the next generation of platinum drugs.

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The research has been conducted with the aim of developing efficient way for nephritis treatment in dogs. After making diagnosis based on the results of clinical, hematological and blood biochemical indices, as well as those of urine research, the treatment was organized per appropriate patterns. The combined application of cyprinol-500, furosemide, galavit and tavegil with antibacterial, diuretic, immuno-stimulating, antihistamine effect, has ensured high therapeutic efficiency in the treatment of dogs’ nephritis.

Enhancing Intersystem Crossing by Intermolecular Dimer-Stacking of Cyanine as Photosensitizer for Cancer Therapy

Enhancing Intersystem Crossing by Intermolecular Dimer-Stacking of Cyanine as Photosensitizer for Cancer Therapy

A Tumor Microenvironment-Triggered and Photothermal-Enhanced Nanocatalysis Multimodal Therapy Platform for Precise Cancer Therapy

The tumor microenvironment (TME)-triggered therapeutic strategy not only provides effective and economical methods for cancer treatment but also minimizes the side effects on normal tissues. However, anticancer species generated by TME-triggered chemical reactions in situ within cancer cells are insufficient to inhibit tumor growth. This study reports the construction of a TME-triggered and photothermal (PT)-enhanced nanocatalysis platform that is based on cancer cell (MCF-7) membrane-camouflaged hollow porous Cu7S4 nanospheres (HPCu7S4@MCF-7) for efficient cancer therapy. HPCu7S4 exhibits strong absorption in the near-infrared region with a high PT conversion efficiency (∼30%). After coating with a cell membrane, HPCu7S4@MCF-7, which possesses a high ability to recognize and target cancer cells, can not only be used as a PT agent for PT therapy (PTT) but can also catalyze the generation of •OH and H2S under TME conditions to facilitate chemodynamic therapy (CDT) and gas therapy (GT), respectively. Moreover, NIR irradiation enhances the generation of more •OH and H2S to improve the therapeutic efficiency. Both in vitro and in vivo results demonstrate a high therapeutic efficiency of HPCu7S4@MCF-7-based PTT in combination with TME-triggered and PT-enhanced CDT and GT, which will open a new approach for constructing multimodal therapeutic strategies for potential use in the clinic.

Circumventing Drug Resistance Pathways with a Nanoparticle-Based Photodynamic Method.

Drug resistance remains the dominant impediment for cancer therapy, not only because compensatory drug resistance pathways are always activated, but also because of the cross-resistance of cancer cells to unrelated therapeutics. Herein, chemodrug-sensitive cancer cells, intrinsic drug-resistant cells, and acquired resistant cells were employed to uncover their biological response to a nanoparticle-based photodynamic method in tumoral, cellular, and molecular levels. We observed that nanoparticle-based photodynamic process with high therapeutic efficiency, intracellular delivery, and tumor penetration effect resulted in the indiscriminate and significant therapeutic outcome, in contrast to the diversiform effect of first-line chemo-drug, Temozolomide (TMZ). By real-time quantitative PCR array technique, we revealed that signals in classical resistance pathways were unaffected or downregulated, and photodynamic effect initiates cell apoptosis via downstream genes. The discovery that nanoparticulate photodynamic therapy bypasses the signals in multiple resistant pathways may imply an alternative route for combating drug resistance of cancer.

Carrier-free nanoparticles of camptothecin prodrug for chemo-photothermal therapy: the making, in vitro and in vivo testing

BackgroundNanoscale drug delivery systems have emerged as broadly applicable approach for chemo-photothermal therapy. However, these nanoscale drug delivery systems suffer from carrier-induced toxicity, uncontrolled drug release and low drug carrying capacity issues. Thus, to develop carrier-free nanoparticles self-assembled from amphiphilic drug molecules, containing photothermal agent and anticancer drug, are very attractive.ResultsIn this study, we conjugated camptothecin (CPT) with a photothermal agent new indocyanine green (IR820) via a redox-responsive disulfide linker. The resulting amphiphilic drug–drug conjugate (IR820-SS-CPT) can self-assemble into nanoparticles (IR820-SS-CPT NPs) in aqueous solution, thus remarkably improving the membrane permeability of IR820 and the aqueous solubility of CPT. The disulfide bond in the IR820-SS-CPT NPs could be cleaved in GSH rich tumor microenvironment, leading to the on demand release of the conjugated drug. Importantly, the IR820-SS-CPT NPs displayed an extremely high therapeutic agent loading efficiency (approaching 100%). Besides, in vitro experimental results indicated that IR820-SS-CPT NPs displayed remarkable tumor cell killing efficiency. Especially, the IR820-SS-CPT NPs exhibited excellent anti-tumor effects in vivo. Both in vitro and in vivo experiments were conducted, which have indicated that the design of IR820-SS-CPT NPs can provide an efficient nanotherapeutics for chemo-photothermal therapy.ConclusionA novel activatable amphiphilic small molecular prodrug IR820-SS-CPT has been developed in this study, which integrated multiple advantages of GSH-triggered drug release, high therapeutic agent content, and combined chemo-photothermal therapy into one drug delivery system.Graphical

Gadolinium delivery agents for neutron capture therapy

<p indent=0mm>Neutron capture therapy (NCT) is a binary form of radiation therapy that combines neutron irradiation with a tumor targeting agent labeled with a stable isotope having a high thermal neutron capture cross section and yielding charged particle reaction products after neutron capture. At present, NCT has largely, but not exclusively, focused on the use of boron-10 as the target nuclide. Gadolinium neutron capture therapy (Gd-NCT) is an alternative and supplementary method of boron neutron capture therapy (BNCT). Gd-157, which has the largest cross-section (254000 barn) of thermal neutrons of all stable isotopes, is the most effective isotope in terms of neutron capture. The Gd neutron capture reaction, ¹⁵⁷Gd(n, γ)¹⁵⁸Gd, provokes complicated nuclear decay transitions that generate low linear energy transfer (LET) gamma photons and the emission of high LET conversion electrons and Auger electrons. Therefore, Gd is considered to be highly suitable for the absorption of thermal neutrons in the NCT reaction. Another advantage of Gd-NCT is Gd³⁺ has a longer retention time and can thus be tracked by means of magnetic resonance imaging (MRI) methods. Currently, Gd(III) based MRI contrast agents are most commonly used in clinical practice. However, due to lack of appropriate tumor-selective Gd agents, the Gd-NCT concept has not yet been clinically tested. For a successful neutron capture therapy, a target nuclide delivery system with high therapeutic efficiency and low adverse effects is crucial. Three major classes Gd delivery agents have been developed so far, small molecule chelates of Gd, nano- delivery agents, and Gd-B dual delivery agents. In the first trial of Gd-NCT, commercially available MRI contrast agents composed of Gd-chelating compounds were used as Gd delivery agents. However, due to the insufficient number of tumor cell nuclei incorporating Gd, efficacy of small molecule chelates of Gd as Gd-NCT delivery agents is generally low. In recent years, with the rapid development of nanotechnology, nanomaterials have been widely employed as carriers for cancer theranostics. A variety of Gd-based nanomaterials have been developed for pre-clinical trials of NCT. Majority of them are constructed by incorporating commercially available MRI contrast agents in biocompatible nanomaterials (liposomes, albumin, and micelles), or employing Gd based nanoparticles with their unique physiochemical properties. While nano-Gd delivery agents have proved to be a promising strategy in Gd-NCT, it is also possible to integrate of both Gd and B in one delivery agent. The design of many Gd-NCT agents to date has focused on combined BNCT and Gd-NCT agents in order to maximise cytotoxicity from the combined effects or to use the B component for NCT and the Gd component as a MRI imaging agent. This paper highlights the recent advances in Gd selective and efficient delivery methods and the preclinical outcome of Gd-NCT, both advantages and disadvantages of various Gd delivery agents were addressed. Finally, we offered our perspectives on the challenges and future development of Gd delivery agents for Gd-NCT.