Theranostic Nanomedicine Research Articles

Advancements in nanotheranostics for glioma therapy.

Gliomas are brain tumors mainly derived from glial cells that are difficult to treat and cause high mortality. Radiation, chemotherapy, and surgical excision are the conventionaltreatments for gliomas. Patients who have surgery or have undergone chemotherapy for glioma treatment have poor prognosis with tumor recurrence. In particular, for glioblastoma,the 5-year averagesurvival rateis 4-7%, and the median survival is 12-18months. Anumber of issues hinder effective treatmentsuch as, poor surgical resection, tumor heterogeneity, insufficient drug penetration across the blood-brain barrier, multidrug resistance, and difficulties with drug specificity. Nanotheranostic-mediated drug delivery is becoming a well-researched consideration, and an efficient non-invasive method for delivering chemotherapeutic drugs to the target area. Theranostic nanomedicines, which incorporate therapeutic drugs and imaging agents forpersonalized therapies, can be used for preventing overdose of non-responders. Through the identification of massive and complicated information from next-generation sequencing, machine learning enables for precise prediction of therapeutic outcomes and post-treatment management for patients with cancer. This article gives a thorough overview of nanocarrier-mediated drug delivery with a brief introduction to drug delivery challenges. In addition, this assessment offers a current summary of preclinical and clinical research on nanomedicines for gliomas. In the future, nanotheranostics will provide personalized treatment for gliomas and other treatable cancers.

Activating Metal-Organic Cages by Incorporating Functional M(ImPhen)3 Metalloligands: From Structural Design to Applications.

ConspectusThe emulation of ingenious biofunctions has been a research focus for several decades. Metal-organic cages (MOCs), as a type of discrete supramolecular assembly with well-defined shapes and cavities, have aroused great interest in chemists to imitate natural protein cages or enzymes. However, to genuinely achieve tailored functionalities or reactivities of enzymes, the design of cage structures combining both the confined microenvironment and the active site is a prerequisite. Therefore, the integration of functionalized motifs into MOCs is expected to provide a feasible approach to construct biofunctional confined nanospaces, which not only allows the modulation of cage properties for applications such as molecular recognition, transport, and catalysis but also creates unique microenvironments that promote enzymatic effects for special reactivities and selectivities, thereby providing a versatile platform to achieve exceptional biomimetic functions and beyond.In this Account, we specifically focus on our research toward engineering active confined-nanospaces in MOCs via incorporation of M(ImPhen)3 metalloligands, a typical tris-chelate coordination moiety comprising imidazophenanthroline ligands and variable metal ions, as the principle functional units for stepwise assembly of active-MOCs. Starting from their structure design and merits, we describe the versatility of M(ImPhen)3 centers for multifunctionalization of the confined cage-nanospaces. By integrating different metal ions like Ru, Os, Fe, Co, Ni, Zn, the metal ion inherent properties, e.g., redox activity of Fe/Co-centers, chirality, and photoactivity of Ru-centers, and dynamics of Co/Zn-centers, could be integrated and tailored on the cages as isostructural nanosized containers or reactors. Changing the Pd or Pt cage vertices to organic clips could remarkably enhance acid-base stability and endow cages with flexibility and allostery. Utilization of ImPhen organic ligands containing imidazole groups introduces proton transfer capability, which can couple with the high-positive charges on the cage to create amphoteric microenvironments in the porous open-cage solution. Moreover, the nonplanar stereoconfiguration of M(ImPhen)3 confers multiple peripheral pockets on the cage, which render multisite, high-order, and dynamics guest binding for the benefit of applications such as drug delivery, molecular separation, and catalytic turnover.The construction of active-MOCs from tailorable M(ImPhen)3 metalloligands provides us with a new perspective on their structural design and functionalities. Merging the cage confinement with distinct physicochemical properties on a supramolecular level makes it practical to realize synergistic and cooperative effects for functionality enhancement beyond molecular components or the reactivity different from the bulky solution, which could largely expand the potential of MOCs as a multirole platform to wide application scenarios such as artificial photosynthesis, unconventional catalysis, and theranostic nanomedicine.

Engineering of exosome-liposome hybrid-based theranostic nanomedicines for NIR-II fluorescence imaging-guided and targeted NIR-II photothermal therapy of subcutaneous glioblastoma

Exosome-liposome hybrid-based vehicles (ELV) are promising carriers for cancer treatment, but there are rare efficient theranostic probes to label their lipid bilayer membrane for precisely tracing biodistribution and execute potent therapy. As both fluorescence imaging and photothermal therapy in the second near-infrared window (NIR-II) has intrinsically deep penetration and high efficacy to ablate tumors, herein the design and synthesis of lipophilic NIR-II cyanine dyes with strong donor strength is reported to label lipid bilayer membrane of ELV for NIR-II fluorescence image-guided and targeted NIR-II photothermal treatment of subcutaneous glioblastoma. Via lipid film hydration and subsequent extrusion method, the synthesized ELV (NIR-C12-EL) is formulated with NIR-C12 labeling, cyclic arginylglycylaspartic acid decoration, liposomal PEGylation, and biological exosome function. NIR-C12-EL exhibits excellent colloidal stability, good biocompatibility, strong light harvesting capability, high NIR-II photoconversion efficiency (62.28 %), and targeting capability to diagnose and ablate tumors, which together contribute to the extended life-span of the mice treatment with NIR-C12-EL and continuous 1064 nm laser irradiation. This study provides insight into not only designing of lipophilic NIR-II fluorescence probes for labeling of exosome-liposome hybrid-based vehicles but also the engineering of theranostic nanoplatforms for precise treatment of glioblastoma.

Biomimetic Dual-Target Theranostic Nanovaccine Enables Magnetic Resonance Imaging and Chemo/Chemodynamic/Immune Therapy of Glioma.

Development of theranostic nanomedicines to tackle glioma remains to be challenging. Here, we present an advanced blood-brain barrier (BBB)-crossing nanovaccine based on cancer cell membrane-camouflaged poly(N-vinylcaprolactam) (PVCL) nanogels (NGs) incorporated with MnO2 and doxorubicin (DOX). We show that the disulfide bond-cross-linked redox-responsive PVCL NGs can be functionalized with dermorphin and imiquimod R837 through cell membrane functionalization. The formed functionalized PVCL NGs having a size of 220 nm are stable, can deplete glutathione, and responsively release both Mn2+ and DOX under the simulated tumor microenvironment to exert the chemo/chemodynamic therapy mediated by DOX and Mn2+, respectively. The combined therapy induces tumor immunogenic cell death to maturate dendritic cells (DCs) and activate tumor-killing T cells. Further, the nanovaccine composed of cancer cell membranes as tumor antigens, R837 as an adjuvant with abilities of DC maturation and macrophages M1 repolarization, and MnO2 with Mn2+-mediated stimulator of interferon gene activation of tumor cells can effectively act on both targets of tumor cells and immune cells. With the dermorphin-mediated BBB crossing, cell membrane-mediated homologous tumor targeting, and Mn2+-facilitated magnetic resonance (MR) imaging property, the designed NG-based theranostic nanovaccine enables MR imaging and combination chemo-, chemodynamic-, and imnune therapy of orthotopic glioma with a significantly decreased recurrence rate.

Mitoxantrone encapsulated photosensitizer nanomicelle as carrier-free theranostic nanomedicine for near-infrared fluorescence imaging-guided chemo-photodynamic combination therapy on cancer

Combination therapy exhibits higher efficacy than any single therapy, inspiring various nanocarrier-assisted multi-drug co-delivery systems for the combined treatment of cancer. However, most nanocarriers are inert and non-therapeutic and have potential side effects. Herein, an amphiphilic polymer composed of a hydrophobic photosensitizer and hydrophilic poly(ethylene glycol) was employed as the nanocarriers and photosensitizers to encapsulate the chemotherapeutic drug mitoxantrone for chemo-photodynamic combination therapy. The resulting nanodrug consisted solely of pharmacologically active ingredients, thus avoiding potential toxicity induced by inert excipients. This multifunctional nanoplatform demonstrated significantly superior treatment performance compared to monotherapy for colorectal cancer, both in vitro and in vivo, achieving near-infrared fluorescence imaging-mediated chemo-photodynamic combined eradication of malignancy.

Peptide‐Based Supramolecular Therapeutics for Fighting Major Diseases

AbstractPeptide‐based supramolecular therapeutics (PST) refer to those theranostic nanomedicines based on peptide or peptide derivatives self‐assembly that are constructed in vitro or in vivo. Benefiting from the inherent advantages of peptides, such as good biocompatibility, high bioactivity, and flexible tunability, the reported PST have shown excellent application prospects in combating many major diseases including cancer, cardiovascular disease, infectious disease, autoimmune disease, metabolic disease, and so on. Through thoughtful design, the PST can be fabricated in various forms, including self‐assembled precursor molecules, functional nano‐assemblies, and macroscopic large‐scale hydrogels. The involved peptides in the PST can play different roles, such as serving drug carriers for effective delivery, acting as scaffold materials for cell culture, and functioning as bioactive sequences for treating diseases. In this review, a comprehensive overview of traditional strategies is provided to build PST and emphasize their therapeutic applications for fighting major diseases that pose a threat to human life and health. Moreover, the main challenges of PST in systems design, therapeutic application, and clinical translation are also briefly discussed. It is hoped that this review can arouse much more attention to be paid for PST and promote its practical application in the biomedical field.

Advances in Atherosclerosis Theranostics Harnessing Iron Oxide-Based Nanoparticles.

Atherosclerosis, a multifaceted chronic inflammatory disease, has a profound impact on cardiovascular health. However, the critical limitations of atherosclerosis management include the delayed detection of advanced stages, the intricate assessment of plaque stability, and the absence of efficacious therapeutic strategies. Nanotheranostic based on nanotechnology offers a novel paradigm for addressing these challenges by amalgamating advanced imaging capabilities with targeted therapeutic interventions. Meanwhile, iron oxide nanoparticles have emerged as compelling candidates for theranostic applications in atherosclerosis due to their magnetic resonance imaging capability and biosafety. This review delineates the current state and prospects of iron oxide nanoparticle-based nanotheranostics in the realm of atherosclerosis, including pivotal aspects of atherosclerosis development, the pertinent targeting strategies involved in disease pathogenesis, and the diagnostic and therapeutic roles of iron oxide nanoparticles. Furthermore, this review provides a comprehensive overview of theranostic nanomedicine approaches employing iron oxide nanoparticles, encompassing chemical therapy, physical stimulation therapy, and biological therapy. Finally, this review proposes and discusses the challenges and prospects associated with translating these innovative strategies into clinically viable anti-atherosclerosis interventions. In conclusion, this review offers new insights into the future of atherosclerosis theranostic, showcasing the remarkable potential of iron oxide-based nanoparticles as versatile tools in the battle against atherosclerosis.

Tumor microenvironment-responsive degradable silica nanoparticles: design principles and precision theranostic applications.

Silica nanoparticles have emerged as promising candidates in the field of nanomedicine due to their remarkable versatility and customizable properties. However, concerns about their potential toxicity in healthy tissues and organs have hindered their widespread clinical translation. To address this challenge, significant attention has been directed toward a specific subset of silica nanoparticles, namely degradable silica nanoparticles, primarily because of their excellent biocompatibility and responsive biodegradability. In this review, we provide a comprehensive understanding of degradable silica nanoparticles, categorizing them into two distinct groups: inorganic species-doped and organic moiety-doped silica nanoparticles based on their framework components. Next, the recent progress of tumor microenvironment (TME)-responsive degradable silica nanoparticles for precision theranostic applications is summarized in detail. Finally, current bottlenecks and future opportunities of theranostic nanomedicines based on degradable silica nanoparticles in clinical applications are also outlined and discussed. The aim of this comprehensive review is to shed light on the potential of degradable silica nanoparticles in addressing current challenges in nanomedicine, offering insights into their design, applications in tumor diagnosis and treatment, and paving the way for future advancements in clinical theranostic nanomedicines.

A Proof-of-Concept Study on the Theranostic Potential of 177 Lu-labeled Biocompatible Covalent Polymer Nanoparticles for Cancer Targeted Radionuclide Therapy.

Theranostic nanomedicine combined bioimaging and therapy probably rises more helpful and interesting opportunities for personalized medicine. In this work, 177 Lu radiolabeling and surface PEGylation of biocompatible covalent polymer nanoparticles (CPNs) have generated a new theranostic nanoformulation (177 Lu-DOTA-PEG-CPNs) for targeted diagnosis and treatment of breast cancer. The in vitro anticancer investigations demonstrate that 177 Lu-DOTA-PEG-CPNs possess excellent bonding capacity with breast cancer cells (4T1), inhibiting the cell viability, leading to cell apoptosis, arresting the cell cycle, and upregulating the reactive oxygen species (ROS), which can be attributed to the good targeting ability of the nanocarrier and the strong relative biological effect of the radionuclide labelled compound. Single photon emission computed tomography/ computed tomography (SPECT/CT) imaging and in vivo biodistribution based on 177 Lu-DOTA-PEG-CPNs reveal that notable radioactivity accumulation at tumor site in murine 4T1 models with both intravenous and intratumoral administration of the prepared radiotracer. Significant tumor inhibition has been observed in mice treated with 177 Lu-DOTA-PEG-CPNs, of which the median survival was highly extended. More strikingly, 50 % of mice intratumorally injected with 177 Lu-DOTA-PEG-CPNs was cured and showed no tumor recurrence within 90 days. The outcome of this work can provide new hints for traditional nanomedicines and promote clinical translation of 177 Lu radiolabeled compounds efficiently.

Nanomedicine-Based Drug-Targeting in Breast Cancer: Pharmacokinetics, Clinical Progress, and Challenges.

Breast cancer (BC) is a malignant neoplasm that begins in the breast tissue. After skin cancer, BC is the second most common type of cancer in women. At the end of 2040, the number of newly diagnosed BC cases is projected to increase by over 40%, reaching approximately 3 million worldwide annually. The hormonal and chemotherapeutic approaches based on conventional formulations have inappropriate therapeutic effects and suboptimal pharmacokinetic responses with nonspecific targeting actions. To overcome such issues, the use of nanomedicines, including liposomes, nanoparticles, micelles, hybrid nanoparticles, etc., has gained wider attention in the treatment of BC. Smaller dimensional nanomedicine (especially 50-200 nm) exhibited improved in vivo effectiveness, such as better tissue penetration and more effective tumor suppression through enhanced retention and permeation, as well as active targeting of the drug. Additionally, nanotechnology, which further extended and developed theranostic nanomedicine by incorporating diagnostic and imaging agents in one platform, has been applied to BC. Furthermore, hybrid and theranostic nanomedicine has also been explored for gene delivery as anticancer therapeutics in BC. Moreover, the nanocarriers' size, shape, surface charge, chemical compositions, and surface area play an important role in the nanocarriers' stability, cellular absorption, cytotoxicity, cellular uptake, and toxicity. Additionally, nanomedicine clinical translation for managing BC remains a slow process. However, a few cases are being used clinically, and their progress with the current challenges is addressed in this Review. Therefore, this Review extensively discusses recent advancements in nanomedicine and its clinical challenges in BC.

Programming assembly of biomimetic exosomes: An emerging theranostic nanomedicine platform.

Exosomes have emerged as a promising cell-free therapeutic approach. However, challenges in large-scale production, quality control, and heterogeneity must be overcome before they can be used clinically. Biomimetic exosomes containing key components of natural exosomes have been assembled through extrusion, artificial synthesis, and liposome fusion to address these limitations. These exosome-mimetics (EMs) possess similar morphology and function but provide higher yields, faster large-scale production, and similar size compared to conventional exosomes. This article provides an overview of the chemical and biological properties of various synthetic exosome systems, including nanovesicles (NVs), EMs, and hybrid exosomes. We highlight recent advances in the production and applications of nanobiotechnology and discuss the advantages, limitations, and potential clinical applications of programming assembly of exosome mimetics.

Radio- and Photosensitizing Os(II)-Based Nanocage for Combined Radio-/Chemo-/X-ray-Induced Photodynamic Therapies, NIR Imaging, and Drug Delivery.

Integration of clinical imaging and collaborative multimodal therapies into a single nanomaterial for multipurpose diagnosis and treatment is of great interest to theranostic nanomedicine. Here, we report a rational design of a discrete Os-based metal-organic nanocage Pd6(OsL3)828+ (MOC-43) as a versatile theranostic nanoplatform to meet the following demands simultaneously: (1) synergistic treatments of radio-, chemo-, and X-ray-induced photodynamic therapies (X-PDT) for breast cancer, (2) NIR imaging for cancer cell tracking and tumor-targeting, and (3) anticancer drug transport through a host-guest strategy. The nanoscale MOC-43 incorporates high-Z Os-element to interact with X-ray irradiation for dual radiosensitization and photosensitization, showing efficient energy transfer to endogenous oxygen in cancer cells to enhance X-PDT efficacy. It also features intrinsic NIR emission originating from metal-to-ligand charge transfer (MLCT) as an excellent imaging probe. Meanwhile, its 12 pockets can capture and concentrate low-water-soluble molecules for anticancer drug delivery. These multifunctions are implemented and demonstrated by micellization of coumarin-loaded cages with DSPE-PEG2000 into coumarin ⊂ MOC-43 nanoparticles (CMNPs) for efficient subcellular endocytosis and uptake. The cancer treatments in vitro/in vivo show promising antitumor performance, providing a conceptual protocol to combine cage-cargo drug transport with diagnosis and treatment for collaborative cancer theranostics by virtue of multifunction synergism on a single-nanomaterial platform.

VEGF mimetic peptide-conjugated nanoparticles for magnetic resonance imaging and therapy of myocardial infarction.

To reduce the mortality of myocardial infarction (MI), accurate detection of the infarct and appropriate prevention against ischemia/reperfusion (I/R) induced cardiac dysfunction are highly desired. Considering that vascular endothelial growth factor (VEGF) receptors are overexpressed in the infarcted heart and VEGF mimetic peptide QK binds specifically to VEGF receptors and activates vascularization, the PEG-QK-modified, gadolinium-doped carbon dots (GCD-PEG-QK) were formulated. This research aims to investigate the magnetic resonance imaging (MRI) capability of GCD-PEG-QK on myocardial infarct and their therapeutic effect on I/R-induced myocardial injury. These multifunctional nanoparticles exhibited good colloidal stability, excellent fluorescent and magnetic property, and satisfactory biocompatibility. Intravenous injection of GCD-PEG-QK nanoparticles post myocardial I/R displayed accurate MRI of the infarct, enhanced efficacy of QK peptide on pro-angiogenesis, and amelioration of cardiac fibrosis, remodeling and dysfunction, probably via the improvement on QK's in vivo stability and MI-targeting. Collectively, the data suggested that this theranostic nanomedicine can realize precise MRI and effective therapy for acute MI in a non-invasive manner.

Facile and controllable synthesis of hematite (α-Fe2O3) nanostructures using GRA-APSO and ANN: Reaction performance optimization for haemotoxicity and MRI assessment

The strategic exploration of a synthetic approach to afford pristine theranostic nanoparticles (NPs) endowed with versatile physicochemical properties depends on their structural attributes. Therefore, optimizing their design while preserving the crystallinity will undoubtedly be a key foundational data to resolve and understand their biophysical and therapeutic properties. Herein, we report a facile synthesis of α-Fe2O3 NPs under different experimental conditions via the co-precipitation technique. An optimization method- grey relational analysis coupled adaptive particle swarm optimization (GRA-APSO) and artificial neural network (ANN)-a modeling tool were employed to optimize and predict the relationship between the input parameters (pH, stirring speed, reaction temperature, and calcination temperature) and the response attributes (crystallite size, lattice strain, crystallinity index, bond length, and band gap). X-ray diffraction (XRD) pattern revealed the hematite crystal structure for NPs synthesized under initial (IE) and optimized (OE) experimental conditions. Transmission electron microscopy (TEM) confirmed the hexagonal shape of α-Fe2O3 NPs with particle size averaging at 8.5 and 13.7 nm for OE and IE, respectively. Brunauer–Emmett–Teller (BET) measurements unveiled the mesoscopic structure of the as-synthesized samples with a high specific surface area (160 m2/g) for OE. The magnetic hysteresis analysis displayed the weak-ferromagnetic nature of α-Fe2O3 samples. Pure α-Fe2O3 NPs exhibited high T2 relaxivity (OE-34.8 and IE-36.4 mM−1s−1). Subsequently, haemocompatibility assays demonstrated excellent compatibility of IE and OE samples toward human RBCs. Moreover, synchronous attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and circular dichroism (CD) measurements proved minimal change in the α-helical content of plasma upon association with α-Fe2O3 NPs. The synergistic outcomes of the present study can promise new avenues for exploring haemocompatible α-Fe2O3 NPs as a novel theranostic nanomedicine for multi-modal imaging and versatile biomedical applications.

Theranostics of metal-organic frameworks: image-guided nanomedicine for clinical translation.

Metal-organic frameworks (MOFs)-based theranostic nanomedicine has demonstrated enormous potential for cancer diagnosis and therapy due to its versatile physiochemical properties, such as structural and morphological properties, specific cellular targeting, tunable pore and particle size, higher surface area, drug-loading capacity, biodegradability and biocompatibility. Notably, MOFs, loaded with diagnostic and therapeutic agents and functionalized with targeting moiety, are capable of catering to both targeted imaging and therapy simultaneously. Additionally, MOFs have demonstrated excellent potential in drug delivery, drug targeting, bioimaging, biosensing, biocatalysis and so on. However, major challenges associated with MOFs include improving their stability, biocompatibility and therapeutic efficacy and reducing the toxicity. This special report sheds light on the historical development, synthesis, recent advancements, toxicity and challenges associated with MOFs-based cancer nanotheranostics for their clinical translation.

Recent Advancements, Challenges, and Future Prospects in Usage of Nanoformulation as Theranostics in Inflammatory Diseases

As of today, chronic inflammatory diseases are a progressive cause of death worldwide, accounting for more than 50% of all fatalities. These inflammatory conditions are a major concern, ranging from heart disease to cancer, diabetes, to even neurodegenerative conditions. Conventional diagnosis and treatment for these problems are often challenging and limited due to complex pathophysiology. To improve upon current treatment and diagnostic strategies, theranostic nanomaterials have been developed. Theranostics is an amalgamation of diagnostic biomarkers and therapeutic medicines that have a shared target in damaged cells or tissues. Different theranostic nanoparticles generate enhanced imaging results for facilities such as MRI, PET scan, and CT scans depending on the site of inflammation in different organs. Furthermore, they can be treated with radiopharmaceuticals and/or medicine in nanoparticles. Following a brief discussion of conventional inflammatory diagnosis and therapeutic strategies, this review will cover the recent progress made in theranostic nanomaterials and nanomedicine tactics for managing inflammatory disorders, covering the preclinical and clinical stages of these advances from the past five years. Furthermore, present challenges with theranostic nanoparticles for inflammatory detection and treatment are discussed, as well as future research possibilities.

Theranostic magnetic nanoparticles: Synthesis, properties, toxicity, and emerging trends for biomedical applications

Nanotechnology provides a wide range of nanosized devices, termed as nanotheranostics, that are integrated with diagnostic and therapeutic properties for real-time monitoring and treatment of diseases. In order to diagnose and cure diseases at the cellular and molecular level, the theranostic nanomedicine must first be able to circulate throughout the body without being destroyed by the host's immune system. Further, this can be linked to a biological ligand for targeting a specific organ or tissue. Novel non-invasive diagnostic agents, such as magnetic nanoparticles (MNPs), are currently employed in magnetic resonance imaging (MRI). Previously, they have been used for imaging various diseases; but new developments have unlocked the way for targeting the drug to the cellular membrane and multi-modal imaging with MNPs. For the production of MNPs, a wide range of synthetic methods such as physical and thermal degradation, hydrothermal production, microemulsion, co-precipitation, and polyol processes have been used, which include few examples of biosynthetic techniques. One of the biggest concern with MNPs is that they have potential toxicity issues in biomedical applications. Due to their reactive surface features and their capacity to penetrate the cell and tissue membranes, MNPs can elicit a powerful cytotoxic effect and hyperthermia. Numerous laboratories have studied in vitro cellular toxicity of MNPs in a wide variety of cancer and normal cell lines, and their findings established the fact that at low concentrations, MNPs are nontoxic, and at high concentrations, they have marginal toxicity, demonstrating their biocompatibility and acceptable safety profile. Diagnostic imaging using nanosystems can be performed using the aforementioned approaches, including MRI, optical imaging, nuclear imaging, computed tomography, ultrasound etc. In this article, various theranostic magnetic nanosystems are discussed in the context of their manufacturing and development for therapeutic and diagnostic use, focusing mainly on in vitro and in vivo applications. Further emphasis on their potential for integrating other nanostructures with current biotechnology, as well as the special qualities of magnetic nanosystems are further highlighted to explain the future role of magnetic nanosystems in the successful therapy.

Gossypol‐Crosslinked Nanoclusters of Ultrasmall Iron Oxide Nanoparticles for Ultrasound‐Enhanced Precision Tumor Theranostics

AbstractDevelopment of tumor microenvironment (TME)‐responsive nanomedicines with simple components for precision tumor theranostics still maintains a great challenge. Here, the design of an intelligent nanocluster (NC) system assembled from gossypol‐mediated crosslinking of phenylboronic acid‐modified ultrasmall iron oxide nanoparticles (USIO NPs) is presented. The gossypol functions as both a chemotherapy (CT) drug and a crosslinker through phenylborate ester bonds that are sensitive to both reactive oxygen species (ROS) and pH. The developed gossypol‐USIO NCs (for short, G‐USIO NCs), having a size of 34.2 nm, possess stability under physiological conditions, enable intracellular ROS generation and glutathione depletion to modulate TME, promote apoptosis of cancer cells in vitro, and inhibit tumor/lung metastasis in vivo through gossypol‐mediated CT and USIO‐mediated chemodynamic therapy owing to the ROS‐ and pH‐triggered dissociation of the NCs to release gossypol and Fe at the tumor site. Likewise, the dissociated USIO NPs from the NCs afford TME‐facilitated T1‐weighted magnetic resonance (MR) imaging. Furthermore, the effects of the tumor T1 MR imaging and the combination therapy can be elevated by ultrasound‐targeted microbubble destruction‐induced cavitation and sonoporation. The designed G‐USIO NCs with simple ingredients are likely developed to be a promising theranostic nanomedicine formulation for ultrasound‐facilitated precision theranostics of various tumor types.

Engineered Sericin-Tagged Layered Double Hydroxides for Combined Delivery of Pemetrexed and ZnO Quantum Dots as Biocompatible Cancer Nanotheranostics.

Despite extensive progress in the field of cancer nanotheranostics, clinical development of biocompatible theranostic nanomedicine remains a formidable challenge. Herein, we engineered biocompatible silk-sericin-tagged inorganic nanohybrids for efficient treatment and imaging of cancer cells. The developed nanocarriers are anticipated to overcome the premature release of the chemotherapeutic drug pemetrexed (PMX), enhance the colloidal stability of layered double hydroxides (LDHs), and maintain the luminescence properties of ZnO quantum dots (QDs). Materials and Methods: PMX-intercalated LDHs were modified with sericin and coupled to ZnO QDs for therapy and imaging of breast cancer cells. Results: The optimized nanomedicine demonstrated a sustained release profile of PMX, and high cytotoxicity against MDA-MB-231 cells compared to free PMX. In addition, high cellular uptake of the engineered nanocarriers into MDA-MB-231 breast cancer cells was accomplished. Conclusions: Conclusively, the LDH-sericin nanohybrids loaded with PMX and conjugated to ZnO QDs offered a promising cancer theranostic nanomedicine.

Biogenic Selenium Nanoparticles in Biomedical Sciences: Properties, Current Trends, Novel Opportunities and Emerging Challenges in Theranostic Nanomedicine.

Selenium is an important dietary supplement and an essential trace element incorporated into selenoproteins with growth-modulating properties and cytotoxic mechanisms of action. However, different compounds of selenium usually possess a narrow nutritional or therapeutic window with a low degree of absorption and delicate safety margins, depending on the dose and the chemical form in which they are provided to the organism. Hence, selenium nanoparticles (SeNPs) are emerging as a novel therapeutic and diagnostic platform with decreased toxicity and the capacity to enhance the biological properties of Se-based compounds. Consistent with the exciting possibilities offered by nanotechnology in the diagnosis, treatment, and prevention of diseases, SeNPs are useful tools in current biomedical research with exceptional benefits as potential therapeutics, with enhanced bioavailability, improved targeting, and effectiveness against oxidative stress and inflammation-mediated disorders. In view of the need for developing eco-friendly, inexpensive, simple, and high-throughput biomedical agents that can also ally with theranostic purposes and exhibit negligible side effects, biogenic SeNPs are receiving special attention. The present manuscript aims to be a reference in its kind by providing the readership with a thorough and comprehensive review that emphasizes the current, yet expanding, possibilities offered by biogenic SeNPs in the biomedical field and the promise they hold among selenium-derived products to, eventually, elicit future developments. First, the present review recalls the physiological importance of selenium as an oligo-element and introduces the unique biological, physicochemical, optoelectronic, and catalytic properties of Se nanomaterials. Then, it addresses the significance of nanosizing on pharmacological activity (pharmacokinetics and pharmacodynamics) and cellular interactions of SeNPs. Importantly, it discusses in detail the role of biosynthesized SeNPs as innovative theranostic agents for personalized nanomedicine-based therapies. Finally, this review explores the role of biogenic SeNPs in the ongoing context of the SARS-CoV-2 pandemic and presents key prospects in translational nanomedicine.