Theranostic Materials Research Articles

Recent Advances in the Design of Biomedical Materials for Cancer Theranostics

Recent Advances in the Design of Biomedical Materials for Cancer Theranostics

Optimizing Multifunctional Phosphors: Thermoluminescence and Luminescence Thermometry Processes

Multifunctional phosphors are extremely important in various applications, ranging from lighting to biomedical purposes. By employing thermoluminescence and luminescence thermometry-related techniques, the intricate processes governing the luminescent behavior of these phosphors can be better understood and controlled.Our study focuses on investigating the thermometric and thermoluminescent properties of Cr3+-activated aluminate family materials, with a specific focus on the effects of co-doping with various lanthanide ions. Through systematic analysis, we aim to understand the influence of lanthanide co-doping on the temperature response and thermoluminescent properties of the phosphors, which can offer valuable insights into using these materials in biological applications.The ultimate goal of our project is to incorporate these functionalized materials into cancer cells and understand their optical characteristics as theranostic materials, as shown in Figure 1. We will comprehensively examine physical processes related to thermo- and persistent luminescence and other thermally stimulated emissions in designed luminescent materials. Our goal is to gain valuable insights into optimizing their functionalities for future bio- and medical applications. The research finances by the Polish National Science Centre under OPUS grant #UMO2023/49/B/ST5/04265. Figure 1

Facile Alkyne Assembly-Enabled Functional Au Nanosheets for Photoacoustic Imaging-Guided Photothermal/Gene Therapy of Orthotopic Glioblastoma.

Treatment of glioblastoma (GBM) remains challenging due to the presence of blood-brain barrier (BBB) and tumor heterogeneity. Herein, Au nanosheets (AuNSs) functionalized with RGD peptides and small interfering RNA (siRNA), referred to as AuNSs-RGD-C≡C-siRNA (ARCR), are prepared to achieve multimodal therapy for GBM. The AuNSs with a large modifiable surface area, intriguing photothermal conversion efficiency (50.26%), and remarkable photothermal stability (44 cycles over 7 h) are created using a well-designed amphiphilic surfactant. Furthermore, alkynyl groups are assembled onto the Au surface within 1 min, enabling strong covalent binding of siRNA to AuNSs and thereby avoiding the interference from biological thiols. Owing to the lipophilicity of the surfactant and the targeting property of RGD, ARCR effectively passes through the BBB and accumulates in GBM tumor regions, allowing near-infrared photoacoustic imaging-guided photothermal/gene therapy. This work proposes a facile strategy to construct theranostic Au-based materials, highlighting the potential of multifunctional nanoagents for GBM therapy.

Applications of Novel Microscale and Nanoscale Materials for Theranostics: From Design to Clinical Translation.

The growing global prevalence of chronic diseases has highlighted the limitations of conventional drug delivery methods, which often suffer from non-specific distribution, systemic toxicity, and poor bioavailability. Microscale and nanoscale materials have emerged as innovative solutions, offering enhanced targeting, controlled release, and the convergence of therapeutic and diagnostic functions, referred to as theranostics. This review explores the design principles, mechanisms of action, and clinical applications of various novel micro- and nanomaterials in diseases such as cancer, cardiovascular disorders, and infectious diseases. These materials enable real-time monitoring of therapeutic responses and facilitate precision medicine approaches. Additionally, this paper addresses the significant challenges hindering clinical translation, including biocompatibility, potential toxicity, and regulatory issues. Ongoing clinical trials demonstrate the potential of nanomaterials in theranostic applications, but further research is needed to overcome the barriers to widespread clinical adoption. This work aims to contribute to the acceleration of integrating nanomedicine into clinical practice, ultimately enhancing the efficacy and safety of therapeutic interventions.

Strongly quenched activatable theranostic nanogel for precision imaging-guided photodynamic therapy and enhanced immunotherapy

Immune checkpoint inhibitors (ICIs) are innovative immunotherapeutic agents for cancer. However, their low therapeutic efficacy in patients with large or rapidly growing tumors, along with their high cost, represents a notable limitation in their clinical applications. Therefore, new and safe strategies must be developed to enhance the therapeutic efficacy of ICIs in clinical settings. In this study, we developed a near-infrared (NIR) fluorescent dye-loaded activatable theranostic nanogel (NATNgel) for precision imaging-guided photodynamic therapy (PDT) and combined immunotherapy for rapidly growing tumors. Although NIR fluorescence and phototoxicity of NATNgel are strongly quenched, these can be selectively activated inside target tumor cells. A high tumor-to-background ratio (7.31 ± 1.40) in NIR fluorescence imaging could be achieved in NATNgel-treated mice, enabling real-time image-guided PDT. The combination of PDT and anti-PD-1 antibody therapy resulted in complete tumor regression. Histopathological evaluation of major organs and blood chemistry analysis revealed no side effects of the combined treatment regimen. In addition, the combination treatment completely suppressed the growth of rechallenged tumors. Overall, NATNgel is a safe and promising theranostic material for precision imaging-guided PDT and enhanced immunotherapy.

Theranostic nano-enabled polyurethane eso-sponges coupled to surface enhanced Raman scattering for detection and control of bacteria killing

Herein, a facile approach toward converting a three-dimensional polyurethane sponge (PUS), employed in endoluminal vacuum-assisted closure (endo-VAC) therapies, in a theranostic material able to detect and to inhibit bacteria growth, has been reported. The endo-VAC PUS presented sensitivity to Gram-positive and Gram-negative bacterial species thanks to its functionalization with gold and silver antibacterial nanoparticles (NPs). PUS with chitosan-stabilized Au-NPs achieved 5.26 ± 0.17 logs and 2.78 ± 0.34 logs of reduction of bacteria growth, whereas the sponges functionalized with phenolated lignin Ag-NPs offered slightly inferior values (4.77 ± 0.36 logs and 2.03 ± 0.37 logs, respectively), against Escherichia coli and Staphylococcus aureus pathogens, respectively, after the application of photothermal ablation. The in vitro antimicrobial studies were contrasted with the in-situ monitoring of bacteria localization and inactivation with excitation lasers of 532 and 785 nm wavelengths, respectively, in the Raman equipment. The novel theranostic nano-enabled antimicrobial PU sponges offer unprecedented possibilities for the improvement of the endo-VAC treatments and extrapolation of the methodology to other plastic-based implants to combat antimicrobial resistances.

Facilitated cell probing and hyperthermia treatment by fluorescent DNA engineered cobalt ferrite nanoparticles

BackgroundProbing a cell by fluorescence imaging is very convenient. We have observed that tagging of DNA with some organic dye molecules enhances fluorescence properties. This property of DNA can be utilised to enhance cell imaging quality to track the cell in better way for diagnosis as well as therapy. ResultsWe have shown internalisation of DNA functionalized cobalt-ferrite nanoparticles (CF-DNA NPs) with cells is better compared to free cobalt-ferrite nanoparticles (CF NPs). Therefore, CF NPs were functionalized by DNA (CF-DNA) and tagged them with a fluorophore like RITC for improvement of cell tracking by fluorescence imaging. Cell imaging and cytotoxicity effects were compared by treating the human mammary carcinoma cells (MDA MB-231) with CF NPs and CF-DNA NPs. An investigation was made on applicability of hyperthermia therapy for these particles under AC magnetic field. SignificancesA significant enhancement in fluorescence contrast of cancer cells was observed in case of CF-DNA NPs compared to CF NPs and both the particles show less cytotoxic effect for normal cells. A significant cell death and change in cell morphology after hyperthermia treatment was observed by phase contrast microscope and scanning electron microscope (SEM). Monitoring the treatment in a selective region is helped by this technique with the use of a very small quantity of theranostic material. This new treatment protocol may open a new avenue in cancer therapy.

Vanadocene-functionalized mesoporous silica nanoparticles: platforms for the development of theranostic materials against breast cancer

Nanoscale materials have demonstrated a very high potential in anticancer therapy by properly adjusting their functionalization and physicochemical properties. Herein, we report the synthesis of some novel vanadocene-loaded silica-based nanomaterials incorporating four different S-containing amino acids (penicillamine, methionine, captopril, and cysteine) and different fluorophores (rhodamine B, coumarin 343 or Alexa Fluor™ 647), which have been characterized by diverse solid-state spectroscopic techniques viz; FTIR, diffuse reflectance spectroscopies, 13C and 51V solid-state NMR spectroscopy, thermogravimetry and TEM. The analysis of the biological activity of the novel vanadocene-based nanostructured silicas showed that the materials containing cysteine and captopril aminoacids demonstrated high cytotoxicity and selectivity against triple negative breast cancer cells, making them very promising antineoplastic drug candidates. According to the biological results it seems that vanadium activity is connected to its incorporation through the amino acid, resulting in synergy that increases the cytotoxic activity against cancer cells of the studied materials presumably by increasing cell internalization. The results presented herein hold significant potential for future developments in mesoporous silica-supported metallodrugs, which exhibit strong cytotoxicity while maintaining low metal loading. They also show potential for theranostic applications highlighted by the analysis of the optical properties of the studied systems after incorporating rhodamine B, coumarin 343 (possible) in vitro anticancer analysis, or Alexa Fluor™ 647 (in vivo studies of cancer models).

Recent advances in mitochondria-targeting theranostic agents.

For its vital role in maintaining cellular activity and survival, mitochondrion is highly involved in various diseases, and several strategies to target mitochondria have been developed for specific imaging and treatment. Among these approaches, theranostic may realize both diagnosis and therapy with one integrated material, benefiting the simplification of treatment process and candidate drug evaluation. A variety of mitochondria-targeting theranostic agents have been designed based on the differential structure and composition of mitochondria, which enable more precise localization within cellular mitochondria at disease sites, facilitating the unveiling of pathological information while concurrently performing therapeutic interventions. Here, progress of mitochondria-targeting theranostic materials reported in recent years along with background information on mitochondria-targeting and therapy have been briefly summarized, determining to deliver updated status and design ideas in this field to readers.

Bonding states of gold/silver plasmonic nanostructures and sulfur-containing active biological ingredients in biomedical applications: a review.

As one of the most instrumental components in the architecture of advanced nanomedicines, plasmonic nanostructures (mainly gold and silver nanomaterials) have been paid a lot of attention. This type of nanomaterial can absorb light photons with a specific wavelength and generate heat or excited electrons through surface resonance, which is a unique physical property. In innovative biomaterials, a significant number of theranostic (therapeutic and diagnostic) materials are produced through the conjugation of thiol-containing ingredients with gold and silver nanoparticles (Au and Ag NPs). Hence, it is essential to investigate Au/Ag-S interfaces precisely and determine the exact bonding states in the active nanobiomaterials. This study intends to provide useful insights into the interactions between Au/Ag NPs and thiol groups that exist in the structure of biomaterials. In this regard, the modeling of Au/Ag-S bonding in active biological ingredients is precisely reviewed. Then, the physiological stability of Au/Ag-based plasmonic nanobioconjugates in real physiological environments (pharmacokinetics) is discussed. Recent experimental validation and achievements of plasmonic theranostics and radiolabelled nanomaterials based on Au/Ag-S conjugation are also profoundly reviewed. This study will also help researchers working on biosensors in which plasmonic devices deal with the thiol-containing biomaterials (e.g., antibodies) inside blood serum and living cells.

X‐Ray Excited Luminescence Materials for Cancer Diagnosis and Theranostics

AbstractX‐rays are rays that penetrate the human tissue and are capable of penetrating water, air, and oxygen in various biological tissues or tumors. In recent years, significant progress has been made in the research of X‐ray‐excited luminescent materials for cancer diagnosis and treatment. In this study, the application of X‐ray‐excited luminescent materials is reviewed for tumor imaging and therapy. First, two classes of luminescent materials are briefly introduced for a form of enhanced X‐ray computed tomography, X‐ray‐excited optical luminescence imaging. Subsequently, the design of multifunctional hybrid materials is evaluated for radiotherapy and other treatments and their synergistic effects under X‐ray excitation are studied. Finally, current key issues and solutions in the field are discussed in detail.

Protein-Engineered Fibers For Drug Encapsulation Traceable via 19F Magnetic Resonance.

Theranostic materials research is experiencing rapid growth driven by the interest in integrating both therapeutic and diagnostic modalities. These materials offer the unique capability to not only provide treatment but also track the progression of a disease. However, to create an ideal theranostic biomaterial without compromising drug encapsulation, diagnostic imaging must be optimized for improved sensitivity and spatial localization. Herein, we create a protein-engineered fluorinated coiled-coil fiber, Q2TFL, capable of improved sensitivity to 19F magnetic resonance spectroscopy (MRS) detection. Leveraging residue-specific noncanonical amino acid incorporation of trifluoroleucine (TFL) into the coiled-coil, Q2, which self-assembles into nanofibers, we generate Q2TFL. We demonstrate that fluorination results in a greater increase in thermostability and 19F magnetic resonance detection compared to the nonfluorinated parent, Q2. Q2TFL also exhibits linear ratiometric 19F MRS thermoresponsiveness, allowing it to act as a temperature probe. Furthermore, we explore the ability of Q2TFL to encapsulate the anti-inflammatory small molecule, curcumin (CCM), and its impact on the coiled-coil structure. Q2TFL also provides hyposignal contrast in 1H MRI, echogenic signal with high-frequency ultrasound and sensitive detection by 19F MRS in vivo illustrating fluorination of coiled-coils for supramolecular assembly and their use with 1H MRI, 19F MRS and high frequency ultrasound as multimodal theranostic agents.

A bifunctional S-doped Fe-N-C nanozyme with excellent oxidase-like activity and photothermal effect for tumor diagnosis and treatment

Tumors have become tremendous threatens to people’s health. However, the development of high-performance theranostic materials, featuring with precise diagnosis and valid treatment, remains great challenges. Herein, S-doped FeNC (FeSNC) nanozyme was prepared by one-pot solvothermal method. The FeSNC exhibited outstanding oxidase-like activity due to the introduction of S. Density functional theory calculation demonstrated that S-doping could not only decrease the adsorption energy to O2 but also change the electron structure of Fe to accelerate the charge transfer between Fe and O, which resulted in the enhancement of the oxidase-like activity of FeSNC. Subsequently, folic acid was grafted on FeSNC for colorimetric detection of tumor cells based on the oxidase-like activity. Tumor cells could be discovered by naked-eyes resulted from the distinct color change. Furthermore, it exhibited excellent linear relationship in the range of 0–2000 and 2000–10000 tumor cells. On the other hand, under the irradiation of near-infrared light, FeSNC showed photothermal conversion performance due to the graphene-like structure of FeSNC, which was capable of killing tumor cells by photothermal therapy effectively. This study not only extends the synthesis method of high-performance nanozyme but also offers a promising strategy to design intelligent and simple platform for tumor diagnosis and treatment.

Unlocking the Stability of Reduced Graphene Oxide Nanosheets in Biological Media via Use of Sodium Ascorbate

AbstractGraphene oxide and reduced graphene oxide (RGO) are carbon bidimensional nanomaterials largely exploited in biomedicine. Their unique interactions with eukaryotic and prokaryotic cells are used to obtain precise intracellular delivery, to create device coatings, and to design theranostic materials for both therapeutic and imaging applications, mainly in the cancer research field. It is known, however, that the hydrophobic behavior of RGO limits its stability in biological media. Here, the employment of sodium ascorbate (NaA) as a reducing agent for the preparation of RGO to provide a nanomaterial with remarkable suitability for applications in cell culture media is proposed. It is demonstrated via a combined experimental and theoretical approach that NaA is able to yield a peculiar RGO derivative, exerting a twofold effect, that is, C sp2 network restoration upon epoxide reduction and RGO edge functionalization via H‐bonding, lending RGO a so far unexampled dispersibility in aqueous‐based media. The kinetic stability of the bidimensional layers of RGO obtained from NaA is demonstrated together with its superior biocompatibility for drug delivery, unlocking outstanding potentialities for biological applications.

Quenching effect in luminescent and magnetic properties of Fe3O4/α-Fe2O3/Y2O3:Eu3+ nanocomposites

In this paper, Fe3O4/α-Fe2O3/Y2O3:Eu3+ multifunctional nanocomposites were synthesized using a hydrothermal method. Fe3O4/α-Fe2O3/Y2O3:Eu3+ nanocomposites are core-shell nanostructures consisting of a superparamagnetic nanomagnetite core, which is converted to hematite during the synthesis. As a theranostic material, hematite could be used in drug-release processes, while nanomagnetite generates heat in a hyperthermia cancer treatment. An outer shell of Y2O3:Eu3+ nanophosphor is added to give nanocomposites photoluminescent properties and to render them visible in bioimaging. Structural, optical, and magnetic features of nanocompositesare studied using X-ray diffraction (XRD), fourier-transform infrared spectroscopy (FTIR), Raman, photoluminescence (PL), vibrating-sample magnetometer (VSM), and high-resolution transmission electron microscope (HRTEM) techniques. Photoluminescence properties of nanocomposites show a quenching effect related to the proportion of magnetite and Y2O3:Eu3+. A luminescence quenching mechanism is proposed based on the optical effects of a core-shell structure. Magnetic saturation grows proportionally with the amount of magnetite present, which indicates that Fe3O4 magnetic structure is not altered, even by the hematite that forms around it. The synthesized nanocomposites possess a core-shell morphology modified by the different proportions of their components. The optical, structural, and magnetic nanocomposite properties found will be of interest in theranostic materials research in the biomedical field.

Dual-response drug released hollow materials for the ultrasonic theranostics of acute myocardial infarction

Acute myocardial infarction (AMI) is a type of serious heart attack. Timely diagnosis and treatment of patients greatly improved their survival and prognosis. Unfortunately, during the progression of AMI, some diagnostic markers, including ST-segment elevation on electrocardiograph and serum troponin, sometimes cannot be obtained changing at an early stage. In addition, the imaging methods such as CT cannot dynamically monitor the AMI. Ultrasound (US) imaging can be considered as a convenient and non-invasive medical diagnosis modality in clinical. But it lacks the targeted ultrasound contrast agent for the diagnosis of AMI. High expression of MMP-9 and ROS was found to be happened with AMI. However, a single targeting of one between them could be interfered by other factors. Here, we successfully synthesized the hollow organic material combining the polymerization of MMP-9 substrate polypeptide and ROS responsive organic compounds in order to have more accuracy targeting to AMI. Dimethyldiethoxysilane (DMDES) was used to achieve colloidal stabilized oil-in-water emulsion template. Thus, the polypeptide and ROS-responsive compound, which have the opposite polarity, can be dissolved in water and oil species, respectively, and react on the surface of these two phases. Moreover, the curcumin (CUR) was also loaded into the hollow material for the targeted release, which realized the theranostics. This material was confirmed with uniform particle size, hollow mesopores, biosafety and ultrasonic imaging enhancement ability both in vitro and in vivo. Furthermore, this material was also demonstrated to have MMP-9 and ROS targeting imaging enhancement and drug releasement both in vitro and in vivo, as well as good therapeutic effects on AMI model cells or mice.

Cooperative Functionalities in Porous Nanoparticles for Seeking Extracellular DNA and Targeting Pathogenic Biofilms via Photodynamic Therapy.

Many pathogenic bacteria are getting more and more resistant against antibiotic treatment and even become up to 1.000× times more resilient in the form of a mature biofilm. Thus, one is currently prospecting for alternative methods for treating microbial infections, and photodynamic therapy is a highly promising approach by creating so-called reactive oxygen species (ROS) produced by a photosensitizer (PS) upon irradiation with light. Unfortunately, the unspecific activity of ROS is also problematic as they are harmful to healthy tissue as well. Notably, one knows that uncontrolled existence of ROS in the body plays a major role in the development of cancer. These arguments create need for advanced theranostic materials which are capable of autonomous targeting and detecting the existence of a biofilm, followed by specific activation to combat the infection. The focus of this contribution is on mesoporous organosilica colloids functionalized by orthogonal and localized click-chemistry methods. The external zone of the particles is modified by a dye of the Hoechst family. The particles readily enter a mature biofilm where adduct formation with extracellular DNA and a resulting change in the fluorescence signal occurs, but they cannot cross cellular membranes such as in healthy tissue. A different dye suitable for photochemical ROS generation, Acridine Orange, is covalently linked to the surfaces of the internal mesopores. The spectral overlap between the emission of Hoechst with the absorption band of Acridine Orange facilitates energy transfer by Förster resonance with up to 88% efficiency. The theranostic properties of the materials including viability studies were investigated in vitro on mature biofilms formed by Pseudomonas fluorescens and prove the high efficacy.

Multifunctional bismuth oxide (Bi2 O3 ) particles: Evidence for selective melanoma therapy.

The current study investigates the therapeutic and optical properties of bismuth oxide (Bi2 O3 ) particles for selective melanoma therapy and prevention. The Bi2 O3 particles were prepared using a standard precipitation method. The Bi2 O3 particles induced apoptosis in human A375 melanoma cells but not human HaCaT keratinocytes or CCD-1090Sk fibroblast cells. This selective apoptosis appears to be associated with a combination of factors: increased particle internalization (2.29 ± 0.41, 1.16 ± 0.08 and 1.66 ± 0.22-fold of control) and enhanced production of reactive oxygen species (ROS) (3.4 ± 0.1, 1.1 ± 0.1 and 2.05 ± 0.17-fold of control) in A375 cells compared to HaCaT and CCD-1090SK cells, respectively. As a high-Z element, bismuth is also an excellent contrast agent for computer tomography, which renders Bi2 O3 a theranostic material. Moreover, Bi2 O3 displays high UV absorption and low photocatalytic activity compared to other semiconducting metal oxides, which opens further potential fields of application as a pigment or as an active ingredient in sunscreens. Overall, this study demonstrates the multifunctional properties of Bi2 O3 particles surrounding the treatment and prevention of melanoma.

Cerium fluoride nanoparticles as a theranostic material for optical imaging of vulnerable atherosclerosis plaques

AbstractAtherosclerosis (AS) is a chronic progressive vascular disease, which can bring on a threat against the health. The eruption of unstable arteriosclerosis plaques has been linked to heart attacks and strokes. The accumulation of foamy macrophages initiates and evolves atherosclerotic plaques, which can be a good target for identifying vulnerable plaques. CD36 and OPN overexpress in foamy macrophages surface, which have a preferable relation with plaque disruption. Furthermore, we choose Yb ions and Tm ions as doping ions and Ce fluoride as matrix of luminescent materials and prepare upconversion luminescent nanoparticles. With the modification of CD36 antibody and OPN antibody, this material can target macrophages in arteriosclerosis plaques. As‐prepared nanoparticles (CeF3:Yb,Tm@SiO2–CD36/OPN) can be excited by near‐infrared light with deep tissue penetration, while emitting strong blue light to image arteriosclerosis plaques. In brief, this study provides a new upconversion luminescent material for the identification and detection of vulnerable atherosclerosis plaques.

Synthesis and optimization of photothermal properties of NIR emitting LiGa5O8: Cr3+ and gold nanorods as hybrid materials for theranostic applications

The increase in incidence of degenerative diseases has fueled the development of novel materials, mostly focused on reducing adverse effects caused by current medical therapies. Theranostic materials represent an alternative to treat degenerative diseases, since they combine diagnostic properties and localized therapy within the same material. This work presents the synthesis and characterization of hybrid materials designed for theranostic purposes. The hybrid materials were composed of LiGa5O8:Cr3+ (LGO) with emission lines in the near infrared (NIR), hence providing an excellent diagnostic ability. As for the therapy part, the hybrid nanomaterials contained gold nanorods (AuR) with localized surface plasmon resonance (LSPR). Once AuR are excited, plasmonic processes are triggered at their surface resulting in increased localized temperature capable of inducing irreversible damage to the cells. A detailed characterization of the hybrid materials confirmed proper assembly of LGO and AuR. Moreover, these nanocomposites preserved their luminescent properties and LSPR. Finally, the cytotoxic potential of the hybrid material was evaluated in different cell lines by cell viability colorimetric assays to determine its possible use as theranostic agent. The success in the synthesis of hybrid materials based on LGO with emission in the NIR coupled with AuR, provides a new perspective for the design of hybrid materials with improved properties to be used in biomedical fields.