All-in-one nanotheranostic platform based on tumor microenvironment: new strategies in multimodal imaging and therapeutic protocol.

Conventional tumor diagnosis and treatment approaches have significant limitations in clinical application, whereas personalized theranostistic nanoplatforms can ensure advanced diagnosis, precise treatment, and even a good prognosis in cancer. Tumor microenvironment (TME)-targeted therapeutic strategies offer absolute advantages in all aspects compared to tumor cell-targeted therapeutic strategies. It is essential to create a TME-responsive all-in-one nanotheranostic platform to facilitate individualized tumor treatment. Based on the TME-responsive multifunctional nanotheranostic platform, we focus on the combined use of multimodal imaging and therapeutic protocols and summary and outlooks on the latest advanced nanomaterials and structures for creating the integrated nanotheranostic system based on material science, which provide insights and reflections on the development of innovative TME-targeting tools for cancer theranostics.

Zinc peroxide-based nanotheranostic platform with endogenous hydrogen peroxide/oxygen generation for enhanced photodynamic-chemo therapy of tumors.

Nanotheranostic platforms, which can respond to tumor microenvironments (TME, such as low pH and hypoxia), are immensely appealing for photodynamic therapy (PDT). However, hypoxia in solid tumors harms the treatment outcome of PDT which depends on oxygen molecules to generate cytotoxic singlet oxygen (1O2). Herein, we report the design of TME-responsive smart nanotheranostic platform (DOX/ZnO2@Zr-Ce6/Pt/PEG) which can generate endogenously hydrogen peroxide (H2O2) and oxygen (O2) to alleviate hypoxia for improving photodynamic-chemo combination therapy of tumors. DOX/ZnO2@Zr-Ce6/Pt/PEG nanocomposite was prepared by the synthesis of ZnO2 nanoparticles, in-situ assembly of Zr-Ce6 as typical metal-organic framework (MOF) on ZnO2 surface, in-situ reduction of Pt nanozymes, amphiphilic lipids surface coating and then doxorubicin (DOX) loading. DOX/ZnO2@Zr-Ce6/Pt/PEG nanocomposite exhibits average sizes of ∼78 nm and possesses a good loading capacity (48.8 %) for DOX. When DOX/ZnO2@Zr-Ce6/Pt/PEG dispersions are intratumorally injected into mice, the weak acidic TEM induces the decomposition of ZnO2 core to generate endogenously H2O2, then Pt nanozymes catalyze H2O2 to produce O2 for alleviating tumor hypoxia. Upon laser (630 nm) irradiation, the Zr-Ce6 component in DOX/ZnO2@Zr-Ce6/Pt/PEG can produce cytotoxic 1O2, and 1O2 generation rate can be enhanced by 2.94 times due to the cascaded generation of endogenous H2O2/O2. Furthermore, the generated O2 can suppress the expression of hypoxia-inducible factor α, and further enable tumor cells to become more sensitive to chemotherapy, thereby leading to an increased effectiveness of chemotherapy treatment. The photodynamic-chemo combination therapy from DOX/ZnO2@Zr-Ce6/Pt/PEG nanoplatform exhibits remarkable tumor growth inhibition compared to chemotherapy or PDT. Thus, the present study is a good demonstration of a TME-responsive nanoplatform in a multimodal approach for cancer therapy.

Tumor microenvironment activated mussel-inspired hollow mesoporous nanotheranostic for enhanced synergistic photodynamic/chemodynamic therapy.

Anti-tumor therapies reliant on reactive oxygen species (ROS) as primary therapeutic agents face challenges due to a limited oxygen substrate. Photodynamic therapy (PDT) is particularly hindered by inherent hypoxia, while chemodynamic therapy (CDT) encounters obstacles from insufficient endogenous hydrogen peroxide (H2O2) levels. In this study, we engineered biodegradable tumor microenvironment (TME)-activated hollow mesoporous MnO2-based nanotheranostic agents, designated as HAMnO2A. This construct entails loading artemisinin (ART) into the cavity and surface modification with a mussel-inspired polymer ligand, namely hyaluronic acid-linked poly(ethylene glycol)-diethylenetriamine-conjugated (3,4-dihydroxyphenyl) acetic acid, and the photosensitizer Chlorin e6 (mPEG-HA-Dien-(Dhpa/Ce6)), facilitating dual-modal imaging-guided PDT/CDT synergistic therapy. In vitro experimentation revealed that HAMnO2A exhibited ideal physiological stability and enhanced cellular uptake capability via CD44-mediated endocytosis. Additionally, it was demonstrated that accelerated endo-lysosomal escape through the pH-dependent protonation of Dien. Within the acidic and highly glutathione (GSH)-rich TME, the active component of HAMnO2A, MnO2, underwent decomposition, liberating oxygen and releasing both Mn2+ and ART. This process alleviates hypoxia within the tumor region and initiates a Fenton-like reaction through the combination of ART and Mn2+, thereby enhancing the effectiveness of PDT and CDT by generating increased singlet oxygen (1O2) and hydroxyl radicals (•OH). Moreover, the presence of Mn2+ ions enabled the activation of T1-weighted magnetic resonance imaging. In vivo findings further validated that HAMnO2A displayed meaningful tumor-targeting capabilities, prolonged circulation time in the bloodstream, and outstanding efficacy in restraining tumor growth while inducing minimal damage to normal tissues. Hence, this nanoplatform serves as an efficient all-in-one solution by facilitating the integration of multiple functions, ultimately enhancing the effectiveness of tumor theranostics.

Nanodiamonds: Next generation nano-theranostics for cancer therapy.

Cancer remains a leading global cause of mortality, demanding early diagnosis and effective treatment. Traditional therapeutic methods often fall short due to their need for more specificity and systemic toxicity. In this challenging landscape, nanodiamonds (ND) emerge as a potential solution, mitigating the limitations of conventional approaches. ND are tiny carbon particles that mimic traditional diamonds chemical stability and hardness and harness nanomaterials' advantages. ND stands out for the unique properties that make them promising nanotheranostics candidates, combining therapeutic and imaging capabilities in one platform. Many of these applications depend on the design of the particle's surface, as the surface's role is crucial in transporting bioactive molecules, preventing aggregation, and building composite materials. This review delves into ND's distinctive features, structural and optical characteristics, and their profound relevance in advancing cancer diagnosis and treatment methods. The report delves into how these exceptional ND properties drive the development of state-of-the-art techniques for precise tumor targeting, boosting the effectiveness of chemotherapy as a chemosensitizer, harnessing immunotherapy strategies, facilitating precision medicine, and creating localized microfilm devices for targeted therapies.

Precision USPIO-PEG-SLex Nanotheranostic Agent Targeted Photothermal Therapy for Enhanced Anti-PD-L1 Immunotherapy to Treat Immunotherapy Resistance.

Background: The anti-Programmed Death-Ligand 1 (termed aPD-L1) immune checkpoint blockade therapy has emerged as a promising treatment approach for various advanced solid tumors. However, the effect of aPD-L1 inhibitors limited by the tumor microenvironment makes most patients exhibit immunotherapy resistance. Methods: We conjugated the Sialyl Lewis X with a polyethylene glycol-coated ultrasmall superparamagnetic iron oxide (USPIO-PEG) to form UPS nanoparticles (USPIO-PEG-SLex, termed UPS). The physicochemical properties of UPS were tested and characterized. Transmission electron microscopy and ICP-OES were used to observe the cellular uptake and targeting ability of UPS. Flow cytometry, mitochondrial membrane potential staining, live-dead staining and scratch assay were used to verify the in vitro photothermal effect of UPS, and the stimulation of UPS on immune-related pathways at the gene level was analyzed by sequencing. Biological safety analysis and pharmacokinetic analysis of UPS were performed. Finally, the amplification effect of UPS-mediated photothermal therapy on aPD-L1-mediated immunotherapy and the corresponding mechanism were studied. Results: In vitro experiments showed that UPS had strong photothermal therapy ability and was able to stimulate 5 immune-related pathways. In vivo, when the PTT assisted aPD-L1 treatment, it exhibited a significant increase in CD4+ T cell infiltration by 14.46-fold and CD8+ T cell infiltration by 14.79-fold, along with elevated secretion of tumor necrosis factor-alpha and interferon-gamma, comparing with alone aPD-L1. This PTT assisted aPD-L1 therapy achieved a significant inhibition of both primary tumors and distant tumors compared to the alone aPD-L1, demonstrating a significant difference. Conclusion: The nanotheranostic agent UPS has been introduced into immunotherapy, which has effectively broadened its application in biomedicine. This photothermal therapeutic approach of the UPS nanotheranostic agent enhancing the efficacy of aPD-L1 immune checkpoint blockade therapy, can be instructive to address the challenges associated with immunotherapy resistance, thereby offering potential for clinical translation.

Multifunctional Nanotheranostics for Dual-Modal Imaging-Guided Precision Therapy of Nasopharyngeal Carcinoma.

Currently, the low survival rate and poor prognosis of patients with nasopharyngeal carcinoma are ascribed to the lack of early and accurate diagnosis and resistance to radiotherapy. In parallel, the integration of imaging-guided diagnosis and precise treatment has gained much attention in the field of theranostic nanotechnology. However, constructing dual-modal imaging-guided nanotheranostics with desired imaging performance as well as great biocompatibility remains challenging. Therefore, we developed a simple but multifunctional nanotheranostic GdCPP for the early and accurate diagnosis and efficient treatment of nasopharyngeal carcinoma (NPC), which combined fluorescence imaging and magnetic resonance imaging (MRI) onto a single nanoplatform for imaging-guided subsequent photodynamic therapy (PDT). GdCPP had an appropriate particle size (81.93 ± 0.69 nm) and was highly stable, resulting in sufficient tumor accumulation, which along with massive reactive oxygen species (ROS) generation upon irradiation further significantly killed tumor cells. Moreover, GdCPP owned much stronger r1 relaxivity (9.396 mM-1 s-1) compared to clinically used Gd-DTPA (5.034 mM-1 s-1) and exhibited better T1WI MRI performance. Under dual-modal imaging-guided PDT, GdCPP achieved efficient therapeutic outcomes without causing any noticeable tissue damage. The results of in vitro and in vivo studies indicated that GdCPP may be a suitable candidate for dual-modal imaging-guided precision tumor therapy.

RNA-Seq Reveals Sex Differences in Gene Expression during Peripheral Neuropathic Inflammation and in Pain Relief from a COX-2 Inhibiting Theranostic Nanoemulsion.

Given decades of neuroinflammatory pain research focused only on males, there is an urgent need to better understand neuroinflammatory pain in females. This, paired with the fact that currently there is no long-term effective treatment for neuropathic pain furthers the need to evaluate how neuropathic pain develops in both sexes and how it can be relieved. Here we show that chronic constriction injury of the sciatic nerve caused comparable levels of mechanical allodynia in both sexes. Using a COX-2 inhibiting theranostic nanoemulsion with increased drug loading, both sexes achieved similar reduction in mechanical hypersensitivity. Given that both sexes have improved pain behavior, we specifically explored differential gene expression between sexes in the dorsal root ganglia (DRG) during pain and relief. Total RNA from the DRG revealed a sexually dimorphic expression for injury and relief caused by COX-2 inhibition. Of note, both males and females experience increased expression of activating transcription factor 3 (Atf3), however, only the female DRG shows decreased expression following drug treatment. Alternatively, S100A8 and S100A9 expression appear to play a sex specific role in relief in males. The sex differences in RNA expression reveal that comparable behavior does not necessitate the same gene expression.

Physico-chemical and MR relaxometry study of bovine serum albumin-coated magneto-plasmonic nanoparticles designed for potential use in cancer nanotheranostics.

PURPOSE: In recent years, the use of nanoparticles has been developed to improve MRI contrast. To improve the contrast agents in image-guided therapy by Multifunctional nanoparticles, in this study, we synthesized a theranostic magneto-plasmonic nanocomplex based on magnetic iron oxide nanoparticles and bovine serum albumin-modified gold nanorod (Au@BSA-Fe3O4@CMD). The purpose of synthesizing these nanoparticles was to use them as MRI contrast agent and photothermal agents in in vitro and in vivo experiments. MATERIALS AND METHODS: Initially, the properties of the synthesized nanoparticles were investigated by methods such as DLS, TEM, FTIR. MTT assay was used to evaluate the toxicity of nanoparticles. Finally, to evaluate the contrast ability of nanoparticles, MRI images were taken in in vitro and in vivo conditions and then the images were analyzed. RESULTS: MTT test results on CT26 cell line showed no significant cytotoxicity for Au@BSA-Fe3O4@CMD nanoparticles at concentrations up to 20 ppm. The in vitro results demonstrated that the Au@BSA-Fe3O4@CMD nanocomplex has high T2 relaxation rate and great relaxivities (r2 = 140.14 mM-1 s-1, r1 = 2.066 mM-1 s-1, r2/r1 = 67.83). For in vivo conditions, a decrease in T2 signal of 9.64 and 11.01, respectively, was observed for intratumoral and intraperitoneal injection of nanoparticles. CONCLUSION: These in vitro and in vivo studies show that Au @ BSA-Fe3O4@CMD nanoparticles can significantly reduce the signal intensity of T2-weight MRI images, and therefore can offer significant potential as a theranostic platform for effective tumor MR imaging.

Organic-Inorganic Hybrid Nanocomposites for Nanotheranostics: Special Focus on Preventing Emerging Variants of SARS-COV-2.

The worldwide emerging cases of various respiratory viral diseases and the current escalation of novel coronavirus disease (COVID-19) make people considerably attentive to controlling these viruses through innovative methods. Most re-emerging respiratory diseases envelop RNA viruses that employ attachment between the virus and host cell to get an entry form using the host cell machinery. Emerging variants of COVD-19 also bring about a constant threat to public health as it has wide infectivity and can quickly spread to infect humans. This review focuses on insights into the current investigations to prevent the progression of incipient variants of Severe Acute Respiratory Syndrome Coronavirus (SARS-COV-2) along with similar enveloped RNA viruses that cause respiratory illness in humans and animals. Nanotheranostics is a trailblazing arena of nanomedicine that simultaneously helps prevent or treat diseases and diagnoses. Nanoparticle coating and nanofibers were extensively explored, preventing viral contaminations. Several studies have proven the virucidal activities of metal nanoparticles like copper, silver, and titanium against respiratory viral pathogens. Worldwide many researchers have shown surfaces coated with ionic nanoparticles like zinc or titanium act as potent antiviral agents against RNA viruses. Carbon nanotubes, quantum dots, silica nanoparticles (NPs), polymeric and metallic nanoparticles have also been explored in the field of nanotheranostics in viral detection. In this review, we have comprehensively discussed different types of metallic, ionic, organic nanoparticles and their hybrids showing substantial antiviral properties to stop the progression of the novel coronavirus disease focused on three key classes: prevention, diagnostics, and treatment.

Multiple therapeutic approaches of glioblastoma multiforme: From terminal to therapy.

Glioblastoma multiforme (GBM) is an aggressive brain cancer showing poor prognosis. Currently, treatment methods of GBM are limited with adverse outcomes and low survival rate. Thus, advancements in the treatment of GBM are of utmost importance, which can be achieved in recent decades. However, despite aggressive initial treatment, most patients develop recurrent diseases, and the overall survival rate of patients is impossible to achieve. Currently, researchers across the globe target signaling events along with tumor microenvironment (TME) through different drug molecules to inhibit the progression of GBM, but clinically they failed to demonstrate much success. Herein, we discuss the therapeutic targets and signaling cascades along with the role of the organoids model in GBM research. Moreover, we systematically review the traditional and emerging therapeutic strategies in GBM. In addition, we discuss the implications of nanotechnologies, AI, and combinatorial approach to enhance GBM therapeutics.

Nanotheranostics: application of nanosensors in diabetes management.

Objectives: The objective of the present study is to discuss the use of nanomaterials like nanosensors for diagnosing Diabetes and highlight their applications in the treatment of Diabetes. Methods: Diabetes mellitus (D.M.) is a group of metabolic diseases characterized by hyperglycemia. Orally administered antidiabetic drugs like glibenclamide, glipalamide, and metformin can partially lower blood sugar levels, but long-term use causes kidney and liver damage. Recent breakthroughs in nanotheranostics have emerged as a powerful tool for diabetes treatment and diagnosis. Results: Nanotheranostics is a rapidly developing area that can revolutionize diabetes diagnosis and treatment by combining therapy and imaging in a single probe, allowing for pancreas-specific drug and insulin delivery. Nanotheranostic in Diabetes research has facilitated the development of improved glucose monitoring and insulin administration modalities, which promise to improve the quality of life for people with Diabetes drastically. Further, nanomaterials like nanocarriers and unique functional nanomaterials used as nano theranostics tools for treating Diabetes will also be highlighted. Conclusion: The nanosensors discussed in this review article will encourage researchers to develop innovative nanomaterials with novel functionalities and properties for diabetes detection and treatment.

Self-assembled multifunctional nanotheranostics against circulating tumor clusters in metastatic breast cancer.

Circulating tumor clusters (CTC) disseminating from the primary tumor are responsible for secondary tumor formation where the conventional treatments such as chemotherapy and radiotherapy does not prevent the metastasis at locally advanced stage of breast cancer. In this study, a smart nanotheranostic system has been developed to track and eliminate the CTCs before it can colonize at a new site, which would reduce metastatic progression and increase the five-year survival rate of the breast cancer patients. Targeted multiresponsive (magnetic hyperthermia and pH) nanomicelles incorporated with NIR fluorescent superparamagnetic iron oxide nanoparticles were developed based on self-assembly for dual modal imaging and dual toxicity for spontaneous killing of CTCs in blood stream. A heterogenous tumor clusters model was developed to mimic the CTCs isolated from breast cancer patients. The nanotheranostic system was further evaluated for the targeting property, drug release kinetics, hyperthermia and cytotoxicity against developed CTC model in vitro. In vivo model in BALB/c mice equivalent to stage III and IV human metastatic breast cancer was developed to evaluate the biodistribution and therapeutic efficacy of micellar nanotheranostic system. Reduced CTCs in blood stream and low distant organ metastasis after treatment with the nanotheranostic system demonstrates its potential to capture and kill the CTCs that minimize the secondary tumor formation at distant sites.

Nanotheranostics for Diagnosis and Treatment of Breast Cancer.

Recently, breast cancer has reached the highest incident rate amongst all the reported cancers, and one of its variants, known as triple-negative breast cancer (TNBC), is deadlier compared to the other types of breast cancer due to a lack of feasible diagnostic techniques. Advancements in nanotechnology have paved the way to formulate several nanocarriers with the ability to deliver anticancer drugs effectively and selectively to cancer cells with minimum side effects to non-cancerous cells. Nanotheranostics is a novel approach that can be used in the diagnosis of disease along with therapeutic effects. Currently, various imaging agents, such as organic dyes, radioactive agents, upconversion nanoparticles, various contrasting agents, quantum dots, etc., are being explored for the imaging of internal organs or to examine drug distribution. Furthermore, ligand-targeted nanocarriers, which have the potential to target cancer sites, are being used as advanced agents for cancer theranostic applications, including the identification of various metastatic sites of the cancerous tumor. This review article discusses the need for theranostic application in breast cancer with various imaging techniques, the latest nanotheranostic carriers in breast cancer, and related safety and toxicity issues, as well as highlights the importance of nanotheranostics in breast cancer, which could be helpful in deciphering questions related to nanotheranostic systems.

A Multifunctional, Highly Biocompatible, and Double-Triggering Caramelized Nanotheranostic System Loaded with Fe3O4 and DOX for Combined Chemo-Photothermal Therapy and Real-Time Magnetic Resonance Imaging Monitoring of Triple Negative Breast Cancer.

Purpose: Owing to lack of specific molecular targets, the current clinical therapeutic strategy for triple negative breast cancer (TNBC) is still limited. In recent years, some nanosystems for malignancy treatment have received considerable attention. In this study, we prepared caramelized nanospheres (CNSs) loaded with doxorubicin (DOX) and Fe3O4 to achieve the synergistic effect of combined therapy and real-time magnetic resonance imaging (MRI) monitoring, so as to improve the diagnosis and therapeutic effect of TNBC. Methods: CNSs with biocompatibility and unique optical properties were prepared by hydrothermal method, DOX and Fe3O4 were loaded on it to obtain Fe3O4/DOX@CNSs nanosystem. Characteristics including morphology, hydrodynamic size, zeta potentials and magnetic properties of Fe3O4/DOX@CNSs were evaluated. The DOX release was evaluated by different pH/near-infrared (NIR) light energy. Biosafety, pharmacokinetics, MRI and therapeutic treatment of Fe3O4@CNSs, DOX and Fe3O4/DOX@CNSs were examined in vitro or in vivo. Results: Fe3O4/DOX@CNSs has an average particle size of 160 nm and a zeta potential of 27.5mV, it demonstrated that Fe3O4/DOX@CNSs is a stable and homogeneous dispersed system. The hemolysis experiment of Fe3O4/DOX@CNSs proved that it can be used in vivo. Fe3O4/DOX@CNSs displayed high photothermal conversion efficiency, extensive pH/heat-induced DOX release. 70.3% DOX release is observed under the 808 nm laser in the pH = 5 PBS solution, obviously higher than pH = 5 (50.9%) and pH = 7.4 (less than 10%). Pharmacokinetic experiments indicated the t1/2ß, and AUC0-t of Fe3O4/DOX@CNSs were 1.96 and 1.31 -fold higher than those of DOX solution, respectively. Additionally, Fe3O4/DOX@CNSs with NIR had the greatest tumor suppression in vitro and in vivo. Moreover, this nanosystem demonstrated distinct contrast enhancement on T2 MRI to achieve real-time imaging monitoring during treatment. Conclusion: Fe3O4/DOX@CNSs is a highly biocompatible, double-triggering and improved DOX bioavailability nanosystem that combines chemo-PTT and real-time MRI monitoring to achieve integration of diagnosis and treatment of TNBC.

Ultra-small NIR-Responsive Nanotheranostic Agent for Targeted Photothermal Ablation Induced Damage-Associated Molecular Patterns (DAMPs) from Post-PTT of Tumor Cells Activate Immunogenic Cell Death.

Theranostic nanoparticles (TNPs) is an efficient avenue that culminates both diagnosis and therapy into cancer treatment. Herein, we have formulated a theranostic nanocomposite (NC) with CuS being the ultra-small core component. To ensure stability to the NC, PEI was added which is a vital anchoring group polymer, especially on sulfide surfaces, and adds quality by being a better stabilizer and reducing agent. Additionally, to add stability, specificity, and added photothermal efficiency to the fabricated NC. In addition, encapsulation of indocyanine green (ICG), an efficient NIR absorber, and Folic acid (FA) were conjugated systematically, characterized, and analyzed for photo-stability. The photothermal conversion efficiency of the novel NC (CuS-PEI-ICG-FA) was analyzed at 808 nm, where the NC efficiently converted light energy to heat energy. The NC was also tested for hemocompatibility to clarify and also determined biocompatibility. Surprisingly, damage-associated molecular patterns (DAMPs) from post-PTT of tumor cells activate immunogenic cell death (ICD) for tumor-specific immune responses. The deserving photothermal performance and photo-stability makes the NC an ideal platform for photoacoustic imaging (PAI). A superior contrast was observed for PAI in a concentration-dependent manner enhancing the level of penetration into tissues, thereby better imaging. On account of this study, the newly formulated NC could be utilized as a "nanotheranostic" designed for therapeutic and image diagnostic agent of cancer biomedical applications.

Self-assembled multifunctional nanotheranostics against circulating tumor clusters in metastatic breast cancer

Circulating tumor clusters (CTC) disseminating from the primary tumor are responsible for secondary tumor formation where the conventional treatments such as chemotherapy and radiotherapy does not prevent the metastasis at locally advanced stage of breast cancer. In this study, a smart nanotheranostic system has been developed to track and eliminate the CTCs before it can colonize at a new site, which would reduce metastatic progression and increase the five-year survival rate of the breast cancer patients. Targeted multiresponsive (magnetic hyperthermia and pH) nanomicelles incorporated with NIR fluorescent superparamagnetic iron oxide nanoparticles were developed based on self-assembly for dual modal imaging and dual toxicity for spontaneous killing of CTCs in blood stream. A heterogenous tumor clusters model was developed to mimic the CTCs isolated from breast cancer patients. The nanotheranostic system was further evaluated for the targeting property, drug release kinetics, hyperthermia and cytotoxicity against developed CTC model in vitro. In vivo model in BALB/c mice equivalent to stage III and IV human metastatic breast cancer was developed to evaluate the biodistribution and therapeutic efficacy of micellar nanotheranostic system. Reduced CTCs in blood stream and low distant organ metastasis after treatment with the nanotheranostic system demonstrates its potential to capture and kill the CTCs that minimize the secondary tumor formation at distant sites.

New anti-cancer explorations based on metal ions.

Due to the urgent demand for more anti-cancer methods, the new applications of metal ions in cancer have attracted increasing attention. Especially the three kinds of the new mode of cell death, including ferroptosis, calcicoptosis, and cuproptosis, are of great concern. Meanwhile, many metal ions have been found to induce cell death through different approaches, such as interfering with osmotic pressure, triggering biocatalysis, activating immune pathways, and generating the prooxidant effect. Therefore, varieties of new strategies based on the above approaches have been studied and applied for anti-cancer applications. Moreover, many contrast agents based on metal ions have gradually become the core components of the bioimaging technologies, such as MRI, CT, and fluorescence imaging, which exhibit guiding significance for cancer diagnosis. Besides, the new nano-theranostic platforms based on metal ions have experimentally shown efficient response to endogenous and exogenous stimuli, which realizes simultaneous cancer therapy and diagnosis through a more controlled nano-system. However, most metal-based agents have still been in the early stages, and controlled clinical trials are necessary to confirm or not the current expectations. This article will focus on these new explorations based on metal ions, hoping to provide some theoretical support for more anti-cancer ideas.

DOTAREM (DOTA)-Gold-Nanoparticles: Design, Spectroscopic Evaluation to Build Hybrid Contrast Agents to Applications in Nanomedecine.

Introduction: The realization of MRI contrast agents through chemical protocols of functionalization is a strong domain of research. In this work, we developed and formulated a novel hybrid gold nanoparticle system in which a gold salt (HAuCl4) is combined with dotarem, an MRI contrast agent (DOTA) by chelation (Method IN) and stabilized by a lactose-modified chitosan polymer (CTL; Chitlac) to form DOTA IN-CTL AuNPs. Result and Discussion: The authors demonstrate the biological efficiency of these nanoparticles in the case of three cell lines: Mia PaCa-2 (human pancreatic cancer cell line), TIB-75 (murine liver cell line) and KKU-M213 (cholangiocarcinoma cell line). DOTA IN-CTL AuNPs are stable under physiological conditions, are nontoxic, and are very efficient as PTT agents. The highlights, such as high stability and preliminary MRI in vitro and in vivo models, may be suitable for diagnosis and therapy. Conclusion: We proved that DOTA IN-CTL AuNPs have several advantages: i) Biological efficacy on three cell lines: MIA PaCa-2 (human pancreatic cancer cell line), TIB-75 (murine liver cell line) and KKU-M213 (cholangiocarcinoma cell line); ii) high stability, and no-toxicity; iii) high efficiency as a PPT agent. The study conducted on MRI in vitro and in vivo models will be suitable for diagnosis and therapy.

Colourful fluorescence-based carbon dots for tumour imaging-guided nanosurgery.

Fluorescent-intraoperative navigation is a visual technique that allows surgeons to accurately distinguish malignant and normal tissues during surgery. It has the advantages of immediacy, high resolution, and high specificity. However, a single fluorescent source cannot provide sufficient surgical information. Multicolour carbon dots (CDs) are more suitable since they provide outstanding water solubility, photostability, and multicolour-fluorescence imaging. Here, we prepared an optical probe with CD-based multicolour-fluorescence imaging via a hydrothermal method. CDs can be endocytosed by tumour cells, and after intravenous injection, they can effectively accumulate at the tumour site. In a pancreatic cancer mouse model, we demonstrated the multicolour-fluorescence imaging capabilities of CDs, which aided the accurate resection of tumours under fluorescent-intraoperative navigation. Stereoscopic fluorescence microscopy imaging and H&E staining proved that the removed tissue belonged to the pancreatic tumour. This study emphasizes the potential of CDs for fluorescence-guided intraoperative resection and expands the application of CDs in biological fields.

Phage Particles of Controlled Length and Genome for In Vivo Targeted Glioblastoma Imaging and Therapeutic Delivery.

M13 bacteriophage (phage) are versatile, genetically tunable nanocarriers that have been recently adapted for use as diagnostic and therapeutic platforms. Applying p3 capsid chlorotoxin fusion with the "inho" circular single-stranded DNA (cssDNA) gene packaging system, we produced miniature chlorotoxin inho (CTX-inho) phage particles with a minimum length of 50 nm that can target intracranial orthotopic patient-derived GBM22 glioblastoma tumors in the brains of mice. Systemically administered indocyanine green conjugated CTX-inho phage accumulated in brain tumors, facilitating shortwave infrared detection. Furthermore, we show that our inho phage can carry cssDNA that are transcriptionally active when delivered to GBM22 glioma cells in vitro. The ability to modulate the capsid display, surface loading, phage length, and cssDNA gene content makes the recombinant M13 phage particle an ideal delivery platform.