Advanced Synthesis, Structural Characterization, and Functional Applications of Precision Polymers.

In the realm of biological macromolecules, entities such as nucleic acids and proteins are distinguished by their homochirality, consistently defined chain lengths, and integral sequence-dependent functionalities. Historically, these refined attributes have eluded traditional synthetic polymers, which often exhibit wide variabilities in chain lengths, limited batch-to-batch reproducibility, and stochastic monomer arrangements. Bridging this divide represents a pivotal challenge within the domain of polymer science-a challenge that the burgeoning discipline of precision polymer chemistry is poised to address. Recent advancements have yielded precision polymers that boast prescribed monomer sequences and narrow molecular weight distributions, heralding a new era for developing model systems to decipher structure-property correlations within functional polymers, analogous to those within biological matrices. This review discusses the innovative liquid-phase and solid-phase synthesis techniques for creating precision polymers and the advanced characterization tools essential for dissecting their structure and properties. We highlight potential applications in self-assembly, catalysis, data storage, imaging, and therapy, and provide insights into the future challenges and directions of precision polymers.

Naphtho[1,8-ef]isoindole-7,8,10(9H)-trione as Novel Theranostic Agents for Photodynamic Therapy and Multi-Subcellular Organelles Localization.

A series of naphtho[1,8-ef]isoindole-7,8,10(9H)-trione derivatives as novel theranostic agents for photodynamic therapy and multi-subcellular organelles localization were designed and synthesized. Most of them possess moderate fluorescence quantum yield and long wavelength absorption simultaneously, which made them possible for dual effects of imaging and therapy. Notably, compounds 7 b and 7 d exhibited significant light-toxicity but slight dark-toxicity. Confocal fluorescence microscopy experiments demonstrated that compound 7 b can locate and image in special multi-subcellular organelles. All the research results implied that naphtho[1,8-ef] isoindole-7,8,10(9H)-trione derivatives can be applied as a new series of theranostic agents with the characteristics of photodynamic therapy and multi-subcellular organelles imaging.

Bifunctional folic acid targeted biopolymer Ag@NMOF nanocomposite [{Zn2 (1,4-bdc) 2 (DABCO)} n] as a novel theranostic agent for molecular imaging of colon cancer by SERS.

Without a doubt, cancer and its negative impact on human health have created many hurdles for people across the world since conventional approaches have not offered a reliable ability in the eradication of cancer. As a result, finding novel approaches, like using bimodal nanoparticles as a potential nanocarrier in molecular imaging and cancer therapy, is remarkably required these days. In the present study, ex-situ (Ge) and in-situ (Gi) green synthesized silver (Ag) nanoparticles entrapped in metal-organic framework nanocomposites (NMOF) coated with folic acid (FA) targeted chitosan (CS) was successfully developed as a novel bifunctional nanocarrier for detection and treatment of colon cancer cells. Then nanocarriers, such as NMOF-CS-FA, Ge-Ag@NMOF-CS-FA, Gi-Ag@NMOF-CS-FA, and C-Ag@NMOF-CS-FA, were characterized via FT-IR, DLS, SERS, TEM, and SEM and results have potentially confirmed the quality and quantity of synthesized nanocomposites. The hydrodynamic diameters of NMOF-CS, Ge-Ag@NMOF-CS, Gi-Ag@NMOF-CS, and C-Ag@NMOF-CS specimens were measured at around 99.7 ± 10 nm, 110 ± 10 nm, 118 ± 10 nm, 115 ± 10 nm, respectively. Also, the PDI values less than 0.2 confirm the reliable distribution of these nanocomposites. Afterward, the cell viability assay was conducted on HCT116 and HGF cell lines for evaluating biocompatibility and targeting efficiency of nanocomposites; FA functionalized nanocomposites have intensively indicated better performance in cancer cells targeting and their inhibition, and IC50 was attained for 10 ng/mL of Ge-Ag@NMOF-CS-FA while non-targeted nanocarriers did not have toxicity more than 20 % on HCT116 colon cancer cells. Moreover, according to the results, the cell viability of HGF normal cells was at least 85 % after being exposed to different concentrations of nanocomposites for 24 h. This indicates that the synthesized nanocomposites do not have significant toxic effects on normal cells. The results indicate that this novel nanocomposite has the potential to effectively deliver drugs to cancer cells.

Engineered photonic near-infrared light activated photothermal theranostic nanovaccine induced targeted remodeling of tumor microenvironment.

Tumor recurrence, which happens as a result of persisting tumor cells and minor lesions after treatments like surgery and chemotherapy, is a major problem in oncology. Herein, a strategy to combat this issue by utilize a theranostic nanovaccine composed of photonic HCuS. This nanovaccine aims to eradicate cancer cells and their traces while also preventing tumor recurrence via optimizing the photothermal immune impact. Successful membrane targeting allows for the introduction of new therapeutic agents into the tumor cells. Together with co-encapsulated Toll-Like Receptors (TLR7/8) agonist R848 for activating T cells and maturing DCs, the combined effects of HCuS and ICG function as photothermal agents that generate heat in the presence of NIR light. Photothermal-mediated immunotherapy with therapeutic modalities proved successful in killing tumor cells. By activating the immune system, this new photonic nanovaccine greatly increases immunogenic cell death (ICD), kills tumor cells, and prevents their recurrence.

Three in One: In Vitro and In Vivo Evaluation of Anticancer Activity of a Theranostic Agent that Combines Magnetic Resonance Imaging, Optical Bioimaging, and Photodynamic Therapy Capabilities.

Cancer treatment is a crucial area of research and development, as current chemotherapeutic treatments can have severe side effects or poor outcomes. In the constant search for new strategies that are localized and minimally invasive and produce minimal side effects, photodynamic therapy (PDT) is an exciting therapeutic modality that has been gaining attention. The use of theranostics, which combine diagnostic and therapeutic capabilities, can further improve treatment monitoring through image guidance. This study explores the potential of a theranostic agent consisting of four Gd(III) DTTA complexes (DTTA: diethylenetriamine-N,N,N″,N″-tetraacetate) grafted to a meso-tetraphenylporphyrin core for PDT, fluorescence, and magnetic resonance imaging (MRI). The agent was first tested in vitro on both nonmalignant TIB-75 and MRC-5 and tumoral CT26 and HT-29 cell lines and subsequently evaluated in vivo in a preclinical colorectal tumor model. Advanced MRI and optical imaging techniques were employed with engineered quantitative in vivo molecular imaging based on dynamic acquisition sequences to track the biodistribution of agents in the body. With 3D quantitative volume computed by MRI and tumoral cell function assessed by bioluminescence imaging, we could demonstrate a significant impact of the molecular agent on tumor growth following light application. Further exhaustive histological analysis confirmed these promising results, making this theranostic agent a potential drug candidate for cancer.

A coumarin-based multifunctional chemosensor for Cu2+/Al3+ as an AD theranostic agent: Synthesis, X-ray single crystal analysis and activity study.

The pathogenesis of Alzheimer's disease (AD) is complex. So far there is no effective drug to treat the disease. The pathological changes of AD began 30 years before symptoms, so early diagnosis is considered to be important for AD treatment. Integrating diagnosis and therapy into a single regent has provided a new opportunity for AD treatment. Given that metal dyshomeostasis is thought to be one of the key factors to cause AD, a Schiff base substituted coumarin (probe 1) has been designed and synthesized as a selective metal chelator for multi-factor anti-AD in this work. The results of metal ions recognition showed that probe 1 had high selective fluorescent turn-on response to Al3+ and fluorescent turn-off response to Cu2+, due to intramolecular charge transfer (ICT) mechanism. Meanwhile, the results of both in vitro and in vivo bioactivities evaluation including metal chelation, reactive oxide species (ROS) elimination, self-/Cu2+-induced Aß aggregation showed that 1 and 1-Cu(II) complex had excellent synergistic anti-AD activities. In addition, 1 had low cytotoxicity and was predicted to cross the blood-brain barrier (BBB). Noticeably, X-ray single crystal diffraction of 1-Cu(II) provided molecular level information to explain the structure and theranostic activity relationship. To sum up, 1 may be a promising candidate for the development of AD theranostic agent.

Upconversion Nanoparticles Intercalated in Large Polymer Micelles for Tumor Imaging and Chemo/Photothermal Therapy.

Frontiers in theranostics are driving the demand for multifunctional nanoagents. Upconversion nanoparticle (UCNP)-based systems activated by near-infrared (NIR) light deeply penetrating biotissue are a powerful tool for the simultaneous diagnosis and therapy of cancer. The intercalation into large polymer micelles of poly(maleic anhydride-alt-1-octadecene) provided the creation of biocompatible UCNPs. The intrinsic properties of UCNPs (core@shell structure NaYF4:Yb3+/Tm3+@NaYF4) embedded in micelles delivered NIR-to-NIR visualization, photothermal therapy, and high drug capacity. Further surface modification of micelles with a thermosensitive polymer (poly-N-vinylcaprolactam) exhibiting a conformation transition provided gradual drug (doxorubicin) release. In addition, the decoration of UCNP micelles with Ag nanoparticles (Ag NPs) synthesized in situ by silver ion reduction enhanced the cytotoxicity of micelles at cell growth temperature. Cell viability assessment on Sk-Br-3, MDA-MB-231, and WI-26 cell lines confirmed this effect. The efficiency of the prepared UCNP complex was evaluated in vivo by Sk-Br-3 xenograft regression in mice for 25 days after peritumoral injection and photoactivation of the lesions with NIR light. The designed polymer micelles hold promise as a photoactivated theranostic agent with quattro-functionalities (NIR absorption, photothermal effect, Ag NP cytotoxicity, and Dox loading) that provides imaging along with chemo- and photothermal therapy enhanced with Ag NPs.

Co2+ Doped Biotinylated Carbon Dot: A Theranostic Agent for Target Specific Killing of Cancer Cells via Hypoxia Induced Apoptosis.

Conventional cancer treatments have systematic side effects that stand against its desirable therapeutic efficacy. Alternative strategies using biochemical features of cancer cells to promote apoptosis are finding notable significance. One such important biochemical feature of malignant cells is hypoxia, alteration of which can lead to cell death. Hypoxia inducible factor 1α (HIF-1α) has the key role in hypoxia generation. Herein, we synthesized biotinylated Co2+ -integrated carbon dot (CoCDb ) that specifically diagnose and selectively killed cancer cells with 3-3.1-fold higher efficiency over non-cancer cells by hypoxia induced apoptosis in absence of traditional therapeutic intervention. Immunoblotting assay in CoCDb treated MDA-MB-231 cells confirmed the increased expression of HIF-1α that was responsible for efficient killing of cancer cells. In 2D cells and 3D tumor spheroid, CoCDb treated cancer cells showed significant apoptosis that make CoCDb a potential theranostic agent.

Recent Advances in Photoacoustic Agents for Theranostic Applications.

Photoacoustic agents are widely used in various theranostic applications. By evaluating the biodistribution obtained from photoacoustic images, the effectiveness of theranostic agents in terms of their delivery efficiency and treatment responses can be analyzed. Through this study, we evaluate and summarize the recent advances in photoacoustic-guided phototherapy, particularly in photothermal and photodynamic therapy. This overview can guide the future directions for theranostic development. Because of the recent applications of photoacoustic imaging in clinical trials, theranostic agents with photoacoustic monitoring have the potential to be translated into the clinical world.

A Review on the Natural Components Applied as Lead Compounds for Potential Multi-target Anti-AD Theranostic Agents.

Alzheimer's disease (AD) is a neurodegenerative disease that seriously affects the health and quality of life of the elderly. Its pathogenesis is very complex and there is still a lack of effective clinical drugs to treat or control the development of AD. Studies have shown that ß-amyloid (Aß) deposition, tau protein hyperphosphorylation, reduced levels of brain cholinergic transmitters, and oxidative stress are the main causes of AD. Furthermore, recent studies showed that metal dyshomeostasis could relate to all the above pathogenesis of AD and was a key factor in the development of AD. Natural compounds and their derivatives have multi-target therapeutic effects on AD, and they also have the advantages of low toxicity, and low cost, which are important directions for anti- AD drugs. Meanwhile, early detection may play an important role in preventing the development of AD. The concept of "theranostic agent" combining molecular imaging probes and therapeutic drugs has emerged in recent years. Fluorescence imaging has been widely studied and applied because of its non-invasive, high resolution, high sensitivity, rapid imaging, and low cost. However, at present, most of the research methods in this field use individual therapeutic or diagnostic reagents, which is not conducive to exploring the optimal treatment time window and drug efficacy. Therefore, this work reviewed the natural compounds and their derivatives which all have been studied for both the in vitro and in vivo therapeutic and diagnostic anti-AD activities. At last, structure and activity relationship (SAR) was discussed and potential AD theranostic natural agents were put forwarded to provide a more detailed theoretical basis for the further development of drugs with diagnostic and therapeutic effects in AD.

T1 Mapping From MPRAGE Acquisitions: Application to the Measurement of the Concentration of Nanoparticles in Tumors for Theranostic Use.

BACKGROUND: The measurement of the concentration of theranostic agents in vivo is essential for the assessment of their therapeutic efficacy and their safety regarding healthy tissue. To this end, there is a need for quantitative T1 measurements that can be obtained as part of a standard clinical imaging protocol applied to tumor patients. PURPOSE: To generate T1 maps from MR images obtained with the magnetization-prepared rapid gradient echo (MPRAGE) sequence. To evaluate the feasibility of the proposed approach on phantoms, animal and patients with brain metastases. STUDY TYPE: Pilot. PHANTOM/ANIMAL MODEL/POPULATION: Solutions containing contrast agents (chelated Gd3+ and iron nanoparticles), male rat of Wistar strain, three patients with brain metastases. FIELD STRENGTH/SEQUENCE: A 3-T and 7-T, saturation recovery (SR), and MPRAGE sequences. ASSESSMENT: The MPRAGE T1 measurement was compared to the reference SR method on phantoms and rat brain at 7-T. The robustness of the in vivo method was evaluated by studying the impact of misestimates of tissue proton density. Concentrations of Gd-based theranostic agents were measured at 3-T in gray matter and metastases in patients recruited in NanoRad clinical trial. STATISTICAL TESTS: A linear model was used to characterize the relation between T1 measurements from the MPRAGE and the SR acquisitions obtained in vitro at 7-T. RESULTS: The slope of the linear model was 0.966 (R2  = 0.9934). MPRAGE-based T1 values measured in the rat brain were 1723 msec in the thalamus. MPRAGE-based T1 values measured in patients in white matter and gray matter amounted to 747 msec and 1690 msec. Mean concentration values of Gd3+ in metastases were 61.47 µmol. DATA CONCLUSION: The T1 values obtained in vitro and in vivo support the validity of the proposed approach. The concentrations of Gd-based theranostic agents may be assessed in patients with metastases within a standard clinical imaging protocol using the MPRAGE sequence. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 1.

Cobalt Ferrite Nanoparticle's Safety in Biomedical and Agricultural Applications: A Review of Recent Progress.

Cobalt ferrite nanoparticles (CFN) have drawn attention as a theranostic agent. Unique physicochemical features of CFN and magnetic properties make CFN an outstanding candidate for biomedical, agricultural, and environmental applications. The extensive use of CFN may result in intentional inoculation of humans for disease diagnosis and therapeutic purposes or unintentional penetration of CFN via inhalation, ingestion, adsorption, or other means. Therefore, understanding the potential cytotoxicity of CFN may pave the way for their future biomedical and agricultural applications. This review scrutinized CFN biocompatibility, possible effects, and cytotoxic mechanisms in different biological systems. Literature indicates CFN toxicity is linked with their size, synthesizing methods, coating materials, exposure time, route of administration, and test concentrations. Some in vitro cytotoxicity tests showed misleading results of CFN potency; this might be due to the interaction of CFN with cytotoxicity assay regents. To date, published research indicates that the biocompatibility of CFN outweighed its cytotoxic effects in plant or animal models, but the opposite outcomes were observed in aquatic Zebrafish.

In vivo behavior of [64Cu]NOTA-terpyridine platinum, a novel chemo-radio-theranostic agent for imaging, and therapy of colorectal cancer.

To overcome resistance to chemotherapy for colorectal cancer, we propose to validate in vivo a novel terpyridine-platinum (TP) compound radiolabeled with the radio-theranostic isotope 64Cu. In vivo stability, biodistribution, PET imaging, tumor growth delay, toxicity and dosimetry of [64Cu]NOTA-C3-TP were determined. The current experimental studies show that [64Cu]NOTA-C3-TP is stable in vivo, rapidly eliminated by the kidneys and has a promising tumor uptake ranging from 1.8 ± 0.4 to 3.0 ± 0.2 %ID/g over 48 h. [64Cu]NOTA-C3-TP retarded tumor growth by up to 6 ± 2.0 days and improved survival relative to vehicle and non-radioactive [NatCu]NOTA-C3-TP over 17 days of tumor growth observation. This effect was obtained with only 0.4 nmol i.v. injection of [64Cu]NOTA-C3-TP, which delivers 3.4 ± 0.3 Gy tumoral absorbed dose. No evidence of toxicity, by weight loss or mortality was revealed. These findings confirm the high potential of [64Cu]NOTA-TP as a novel radio-theranostic agent.

Antibacterial Theranostic Agents with Negligible Living Cell Invasiveness: AIE-Active Cationic Amphiphiles Regulated by Alkyl Chain Engineering.

To address the threat of bacterial infection in the following post-antibiotic era, developing effective antibacterial approaches is of utmost urgency. Theranostic medicine integrating diagnosis and therapy is a promising protocol to fight against pathogenic bacteria. But numerous reported antibacterial theranostic materials are disclosed to be trapped in the excessive invasiveness to living mammal cells, leading to false positives and possible biosafety risks. Herein, a series of cationic pyridinium-substituted phosphindole oxide derivatives featuring aggregation-induced emission are designed, and alkyl chain engineering is conducted to finely tune their hydrophobicity and investigate their bioaffinity preference for living mammal cells and pathogenic bacteria. Most importantly, an efficient theranostic agent (PyBu-PIO) is acquired that is free from living cell invasiveness with negligible cytotoxicity and yet holds a good affinity for Gram-positive bacteria, including drug-resistant strains, with a superior inactivating effect. Externally applying PyBu-PIO onto Gram-positive bacteria-infected skin wounds can achieve creditable imaging effects and successfully accelerate the healing processes with reliable biosafety. This work proposes living cell invasiveness as a criterion for antibacterial theranostic materials and provides important enlightenment for the design of antibacterial theranostic materials.

Fe-Based Theranostic Agents Respond to the Tumor Microenvironment for MRI-Guided Ferroptosis-/Apoptosis-Inducing Anticancer Therapy.

Tumor microenvironment-specific magnetic resonance imaging (MRI) contrast agents are conducive to accurate diagnoses by visualization of biochemical and pathological changes for suitable treatment. Herein, we reported a pH-responsive contrast agent DFeZd NP with MRI diagnosis and tumor treatment capabilities. DFeZd NPs can map the pH change by modulating the MR signal in different acid-base environments. Moreover, T1 signals are stronger in the tumor site, which proves efficient in distinguishing malignant tumors from normal tissues, as well as demarcating the tumor boundary. Subsequently, sustained supply of Fe through the Fe-based contrast agent leads to Fe redox cycling and lipid peroxides, inducing ferroptosis in tumor cells. Furthermore, under an acidic tumor microenvironment, in the presence of ascorbic acid, increased Fe2+ is generated, which serves as a stronger inducer of ferroptosis. Moreover, due to the different relaxivity of Fe3+ and Fe2+, redox cycling and ferroptosis in tumors can be monitored by MRI. Therefore, we propose DFeZd NPs as accessible and promising Fe-based dopamine-derived contrast agents for specific MRI imaging and ferroptosis induction for anticancer therapy.

Stimuli-responsive theranostic system: A promising approach for augmented multimodal imaging and efficient drug release.

Destruction of drug resistant and invisible micro-tumors requires innovative screening and treatment modalities. Theranostic nanosystems offering multimodal imaging and therapy are attractive platforms with potential to make micro-tumors visible to clinicians. Gold nanoparticles (AuNPs) are intrinsic theranostic agents and act as fluorescence quenchers. They can be easily transformed to multimodal imaging and combination therapy agents by combining them with various adjuvant therapies such as photodynamic therapy. In this study, we developed a highly specific, hybrid theranostic agent that is only activated when it meets with its stimuli at the site of interest. Surface-coated AuNPs were modified with Cathepsin B cleavable peptide (stimuli responsive linker) and Verteporfin (photosensitizer and fluorescence imaging agent). Unless the theranostic system meets with the internal stimuli in tumor cells, fluorescence is quenched due to AuNP-Verteporfin and Verteporfin-Verteporfin interactions. Following cellular internalization of the theranostic agent, fluorescence is gained by Cathepsin B cleavage and phototoxicity is initiated by light. The system was efficiently internalized by SKOV-3 cells and demonstrated high specificity towards its stimuli. In comparison to Verteporfin, ∼14-fold fluorescence increase, 81% fluorescence recovery and comparable toxicity were achieved. The system is a promising candidate for multimodal imaging and dual treatment to destroy the micro-tumors.

TME-targeting theranostic agent uses NIR tracking for tumor diagnosis and surgical resection and acts as chemotherapeutic showing enhanced efficiency and minimal toxicity.

Rationale: Precise diagnosis and effective therapy of the tumor microenvironment (TME) remains a challenge. Fluorescence tracers for monitoring primary tumors are currently reported; however, they face challenges in accurately delineating tumors in real-time during surgery, including interference from the background and insufficient accumulation of imaging reagents at tumor sites. Additionally, although the natural product podophyllotoxin (PPT) had potent and broad anti-tumor activity, the poor tumor target specificity and high toxicity of PPT extremely limited its clinical application. Methods: In the current study, a novel theranostic agent PBB was designed and synthesized by coupling the natural chemotherapeutic drug PPT with a near-infrared (NIR) fluorescence probe hemicyanine (CyOH) via redox-responsive thiolactate linker and introducing biotin to CyOH to enhance the active target ability. The activation mechanism of PBB was characterized by absorption spectra, fluorescence spectra, and HPLC. Subsequently, we investigated its imaging action, anti-tumor activity, and toxicity in vitro and in vivo. Results:In vitro experiments, PBB was verified to possess a ROS/GSH-responsive molecular switch, impelling PBB to release a fluorescent fragment and active drug PPT and selectively lighting up tumor cells but not the normal cells. As such, PBB was demonstrated to selectively inhibit the growth of tumor cells by inducing intracellular accumulation of ROS and MMP depolarization. More importantly, PBB significantly suppressed hepatic tumor growth and minimized the adverse effects caused by PPT, including acute toxicity and impaired liver function. Finally, the NIR fluorescence accumulated in the tumor tissue and stayed continuous for over 24h, and PBB provided precise visualization and highly selective fluorescence diagnosis to guide tumor resection. Conclusions: Therefore, the multilevel targeting theranostic agent provided a novel tool for precise diagnosis, real-time monitoring, and efficient tumor chemotherapy with high safety.

A multifunctional metal regulator as the potential theranostic agent: Design, synthesis, anti-AD activities and metallic ion sensing properties.

Although there is no cure for Alzheimer's disease (AD) due to its complex pathogenesis, early detection and treatment can help delay the development of the disease. So, it is necessary to develop multifunctional metal regulators that can integrate the therapeutics and diagnostics effect against AD. In this work, N-(anthracene-9-ylmethylene)benzohydrazide (probe 1), a fluorescent probe with imine and carbonyl as chelating sites was designed and synthesized. Results showed that 1 had good activities related to AD, such as regulation of metal homeostasis, inhibition of ß-amyloid (Aß) aggregation and scavenging of reactive oxygen species. The selectivity experiment showed that probe 1 had a good recognition effect on Cu2+. Fluorescence imaging assay also indicated that probe 1 had a good fluorescence imaging effect on Cu2+ in living cells. Furthermore, probe 1 had showed no cytotoxicity and good BBB permeability. These results indicated that probe 1 had potential diagnostic and therapeutic capabilities, and can be used as the multifunctional theranostic agent for AD.

Targeted Phototherapy by Niobium Carbide for Mammalian Tumor Models Similar to Humans.

BACKGROUND: In the past few decades, nanomaterial-mediated phototherapy has gained significant attention as an alternative antitumor strategy. However, its antitumor success is majorly limited to the treatment of subcutaneous tumors in nude mice. In fact, no studies have been previously conducted in this area/field on clinically-relevant big animal models. Therefore, there is an urgent need to conduct further investigation in a typical big animal model, which is more closely related to the human body. RESULTS: In this study, niobium carbide (NbC) was selected as a photoactive substance owing to the presence of outstanding near-infrared (NIR) absorption properties, which are responsible for the generation of NIR-triggered hyperthermia and reactive oxygen species that contribute towards synergetic photothermal and photodynamic effect. Moreover, the present study utilized macrophages as bio-carrier for the targeted delivery of NbC, wherein phagocytosis by macrophages retained the photothermal/photodynamic effect of NbC. Consequently, macrophage-loaded NbC ensured/allowed complete removal of solid tumors both in nude mice and big animal models involving rabbits. Meanwhile, two-dimensional ultrasound, shave wave elastography (SWE), and contrast-enhanced ultrasound (CEUS) were used to monitor physiological evolution in tumor in vivo post-treatment, which clearly revealed the occurrence of the photoablation process in tumor and provided a new strategy for the surveillance of tumor in big animal models. CONCLUSION: Altogether, the use of a large animal model in this study presented higher clinical significance as compared to previous studies.

Biomedical Applications of Metal-Organic Frameworks for Disease Diagnosis and Drug Delivery: A Review.

Metal-organic frameworks (MOFs) are a novel class of porous hybrid organic-inorganic materials that have attracted increasing attention over the past decade. MOFs can be used in chemical engineering, materials science, and chemistry applications. Recently, these structures have been thoroughly studied as promising platforms for biomedical applications. Due to their unique physical and chemical properties, they are regarded as promising candidates for disease diagnosis and drug delivery. Their well-defined structure, high porosity, tunable frameworks, wide range of pore shapes, ultrahigh surface area, relatively low toxicity, and easy chemical functionalization have made them the focus of extensive research. This review highlights the up-to-date progress of MOFs as potential platforms for disease diagnosis and drug delivery for a wide range of diseases such as cancer, diabetes, neurological disorders, and ocular diseases. A brief description of the synthesis methods of MOFs is first presented. Various examples of MOF-based sensors and DDSs are introduced for the different diseases. Finally, the challenges and perspectives are discussed to provide context for the future development of MOFs as efficient platforms for disease diagnosis and drug delivery systems.