Designing Green Synthesis-Based Silver Nanoparticles for Antimicrobial Theranostics and Cancer Invasion Prevention.

Introduction: Researchers are increasingly favouring the use of biological resources in the synthesis of metallic nanoparticles. This synthesis process is quick and affordable. The current study examined the antibacterial and anticancer effects of silver nanoparticles (AgNPs) derived from the Neurada procumbens plant. Biomolecules derived from natural sources can be used to coat AgNPs to make them biocompatible. Methods: UV-Vis spectroscopy was used to verify the synthesis of AgNPs from Neurada procumbens plant extract, while transmission electron microscopy (TEM), photoluminescence (PL) spectroscopy, dynamic light scattering (DLS), and Fourier transform infrared spectroscopy (FTIR) were used to characterize their morphology, crystalline structure, stability, and coating. Results: UV-visible spectrum of AgNPs shows an absorption peak at 422 nm, indicating the isotropic nature of these nanoparticles. As a result of the emergence of a transmission peak at 804.53 and 615.95 cm-1 in the spectrum of the infrared light emitted by atoms in a sample, FTIR spectroscopy demonstrated that the Ag stretching vibration mode is metal-oxygen (M-O). Electron dispersive X-ray (EDX) spectral analysis shows that elementary silver has a peak at 3 keV. Irradiating the silver surface with electrons, photons, or laser beams triggers the illumination. The emission peak locations have been found between 300 and 550 nm. As a result of DLS analysis, suspended particles showed a bimodal size distribution, with their Z-average particle size being 93.38 nm. Conclusion: The findings showed that the antibacterial action of AgNPs was substantially (p≤0.05) more evident against Gramme-positive strains (S. aureus and B. cereus) than E. coli. The biosynthesis of AgNPs is an environmentally friendly method for making nanostructures that have antimicrobial and anticancer properties.

Advances in Gold Nanoparticles: Synthesis, Functionalization Strategies, and Theranostic Applications in Cancer.

Cancer is among the leading causes of mortality and morbidity in the world. Metallic nanoparticles, especially gold nanoparticles (AuNPs) have emerged to be attractive systems to circumvent the associated adverse effects. By the virtue of their unique properties of tunable size, shape, composition, optical properties, biocompatibility, minimal toxicity, multivalency, fluorescence-luminescence property and surface plasmon resonance; AuNPs have the potential to be used as drug delivery systems. It is vital to ensure that the drug reaches the target site of action for selective kill of cancer cells without harm to healthy cells. These AuNPs can be easily functionalized with a wide array of ligands like peptides, oligonucleotides, polymers, carbohydrates for active targeting to ensure site specific delivery and reduced systemic effects. AuNPs have been in-vestigated as carriers for gene delivery, drug delivery with or without photothermal therapy, in diagnosis based on radiation or spectroscopy. They have emerged as attractive theranostic approach in the overall management of cancer with superior benefit to risk features. In this review, we have discussed synthesis of different AuNPs (nanorods, spherical nanoparticles, and hollow AuNPs), their functionalization strategies and their applications in biomedical domain. Various research studies and clinical trials on application of AuNPs in diagnosis and therapeutics are highlighted.

Acid-Triggered Degradation of Three-In-One Ag2S Quantum Dots for In Situ Ratiometric NIR-II Fluorescence Imaging-Guided Ion/Gas Combination Therapy.

Smart theranostic nanoprobes with the integration of multiple therapeutic modalities are preferred for precise diagnosis and efficient therapy of tumors. However, it remains a big challenge to arrange the imaging and two or more kinds of therapeutic agents without weakening the intended performances. In addition, most existing fluorescence (FL) imaging agents suffer from low spatiotemporal resolution due to the short emission wavelength (<900 nm). Here, novel three-in-one Ag2S quantum dot (QD)-based smart theranostic nanoprobes were proposed for in situ ratiometric NIR-II FL imaging-guided ion/gas combination therapy of tumors. Under the acidic tumor microenvironment, three-in-one Ag2S QDs underwent destructive degradation, generating toxic Ag+ and H2S. Meanwhile, their FL emission at 1270 nm was weakened. Upon introduction of a downconversion nanoparticle (DCNP) as the delivery carrier and NIR-II FL reference signal unit, the formed Ag2S QD-based theranostic nanoprobes could achieve precise diagnosis of tumors through ratiometric NIR-II FL signals. Also, the generated Ag+ and H2S enabled specific ion/gas combination therapy toward tumors. By combining the imaging and therapeutic functions, three-in-one Ag2S QDs may open a simple yet reliable avenue to design theranostic nanoprobes.

Ultrasmall Fe3O4 nanoparticles self-assembly induced dual-mode T1/T2-weighted magnetic resonance imaging and enhanced tumor synergetic theranostics.

Individual theranostic agents with dual-mode MRI responses and therapeutic efficacy have attracted extensive interest due to the real-time monitor and high effective treatment, which endow the providential treatment and avoid the repeated medication with side effects. However, it is difficult to achieve the integrated strategy of MRI and therapeutic drug due to complicated synthesis route, low efficiency and potential biosafety issues. In this study, novel self-assembled ultrasmall Fe3O4 nanoclusters were developed for tumor-targeted dual-mode T1/T2-weighted magnetic resonance imaging (MRI) guided synergetic chemodynamic therapy (CDT) and chemotherapy. The self-assembled ultrasmall Fe3O4 nanoclusters synthesized by facilely modifying ultrasmall Fe3O4 nanoparticles with 2,3-dimercaptosuccinic acid (DMSA) molecule possess long-term stability and mass production ability. The proposed ultrasmall Fe3O4 nanoclusters shows excellent dual-mode T1 and T2 MRI capacities as well as favorable CDT ability due to the appropriate size effect and the abundant Fe ion on the surface of ultrasmall Fe3O4 nanoclusters. After conjugation with the tumor targeting ligand Arg-Gly-Asp (RGD) and chemotherapy drug doxorubicin (Dox), the functionalized Fe3O4 nanoclusters achieve enhanced tumor accumulation and retention effects and synergetic CDT and chemotherapy function, which serve as a powerful integrated theranostic platform for cancer treatment.

Cucurbit[8]uril-based supramolecular theranostics.

Different from most of the conventional platforms with dissatisfactory theranostic capabilities, supramolecular nanotheranostic systems have unparalleled advantages via the artful combination of supramolecular chemistry and nanotechnology. Benefiting from the tunable stimuli-responsiveness and compatible hierarchical organization, host-guest interactions have developed into the most popular mainstay for constructing supramolecular nanoplatforms. Characterized by the strong and diverse complexation property, cucurbit[8]uril (CB[8]) shows great potential as important building blocks for supramolecular theranostic systems. In this review, we summarize the recent progress of CB[8]-based supramolecular theranostics regarding the design, manufacture and theranostic mechanism. Meanwhile, the current limitations and corresponding reasonable solutions as well as the potential future development are also discussed.

A Nanorobotics-Based Approach of Breast Cancer in the Nanotechnology Era.

We are living in an era of advanced nanoscience and nanotechnology. Numerous nanomaterials, culminating in nanorobots, have demonstrated ingenious applications in biomedicine, including breast cancer (BC) nano-theranostics. To solve the complicated problem of BC heterogeneity, non-targeted drug distribution, invasive diagnostics or surgery, resistance to classic onco-therapies and real-time monitoring of tumors, nanorobots are designed to perform multiple tasks at a small scale, even at the organelles or molecular level. Over the last few years, most nanorobots have been bioengineered as biomimetic and biocompatible nano(bio)structures, resembling different organisms and cells, such as urchin, spider, octopus, fish, spermatozoon, flagellar bacterium or helicoidal cyanobacterium. In this review, readers will be able to deepen their knowledge of the structure, behavior and role of several types of nanorobots, among other nanomaterials, in BC theranostics. We summarized here the characteristics of many functionalized nanodevices designed to counteract the main neoplastic hallmark features of BC, from sustaining proliferation and evading anti-growth signaling and resisting programmed cell death to inducing angiogenesis, activating invasion and metastasis, preventing genomic instability, avoiding immune destruction and deregulating autophagy. Most of these nanorobots function as targeted and self-propelled smart nano-carriers or nano-drug delivery systems (nano-DDSs), enhancing the efficiency and safety of chemo-, radio- or photodynamic therapy, or the current imagistic techniques used in BC diagnosis. Most of these nanorobots have been tested in vitro, using various BC cell lines, as well as in vivo, mainly based on mice models. We are still waiting for nanorobots that are low-cost, as well as for a wider transition of these favorable effects from laboratory to clinical practice.

Theranostics in Neuroendocrine Tumors.

ABSTRACT: Neuroendocrine tumors (NETs) are rare tumors that develop from cells of the neuroendocrine system and can originate in multiple organs and tissues such as the bowels, pancreas, adrenal glands, ganglia, thyroid, and lungs. This review will focus on gastroenteropancreatic NETs (more commonly called NETs) characterized by frequent somatostatin receptor (SSTR) overexpression and pheochromocytomas/paragangliomas (PPGLs), which typically overexpress norepinephrine transporter. Advancements in SSTR-targeted imaging and treatment have revolutionized the management of patients with NETs. This comprehensive review delves into the current practice, discussing the use of the various Food and Drug Administration-approved SSTR-agonist positron emission tomography tracers and the predictive imaging biomarkers, and elaborating on 177Lu-DOTATATE peptide receptor radionuclide therapy including the evolving areas of posttherapy imaging practices and peptide receptor radionuclide therapy retreatment. SSTR-targeted imaging and therapy can also be used in patients with PPGL; however, this patient population has demonstrated the best outcomes from norepinephrine transporter-targeted therapy with 131I-metaiodobenzylguanidine. Metaiodobenzylguanidine theranostics for PPGL will be discussed, noting that in 2024 it became commercially unavailable in the United States. Therefore, the use and reported success of SSTR theranostics for PPGL will also be explored.

Self-enhanced regulation of stable organic radicals with polypeptide nanoparticles for mild second near-infrared phototheranostics.

Stable organic radicals have emerged as a promising option to enhance fluorescence quantum yield (QY), gaining traction in medical treatment due to their unique electronic transitions from the ground state (D0) to the doublet excited state (D1). We synthesized a stable dicyanomethyl radical with a NIR-II fluorescence QY of 0.86 %, surpassing many NIR-II organic dyes. Subsequently, amphiphilic polymer-encapsulated nanoparticles (NPs) containing the radical were created, achieving a NIR-II fluorescence QY of 0.32 %, facilitating high-contrast bio-imaging. These CNPPs exhibit self-enhanced photothermal properties, elevating photothermal conversion efficiency (PCE) from 43.5 % to 57.5 % under 915 nm laser irradiation. This advancement enables more efficient photothermal therapy (PTT) with lower dye concentrations and reduced laser power, enhancing both feasibility and safety. Through regular fractionated mild photothermal therapy, we observed the release of damage-associated molecular patterns (DAMPs) and an increase in cytokine expression, culminating in combined mild phototherapy (m-PTT)-mediated immunogenic cell death (ICD). Consequently, we developed an immunostimulatory tumor vaccine, showcasing a novel approach for refining photothermal agents (PTA) and optimizing the PTT process.

Three musketeers of PDA-based MRI contrasting and therapy.

Polydopamine (PDA) stands as a versatile material explored in cancer nanomedicine for its unique properties, offering opportunities for multifunctional drug delivery platforms. This study explores the potential of utilizing a one-pot synthesis to concurrently integrate Fe, Gd and Mn ions into porous PDA-based theranostic drug delivery platforms called Ferritis, Gadolinis and Manganis, respectively. Our investigation spans the morphology, magnetic properties, photothermal characteristics and cytotoxicity profiles of those potent nanoformulations. The obtained structures showcase a spherical morphology, robust magnetic response and promising photothermal behaviour. All of the presented nanoparticles (NPs) display pronounced paramagnetism, revealing contrasting potential for MRI imaging. Relaxivity values, a key determinant of contrast efficacy, demonstrated competitive or superior performance compared to established, used contrasting agents. These nanoformulations also exhibited robust photothermal properties under near infra-red irradiation, showcasing their possible application for photothermal therapy of cancer. Our findings provide insights into the potential of metal-doped PDA NPs for cancer theranostics.

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.

Two-Photon Absorption Aggregation-Induced Emission Luminogen/Paclitaxel Nanoparticles for Cancer Theranostics.

Multifaceted nanoplatforms integrating fluorescence imaging and chemotherapy have garnered acknowledgment for their potential potency in cancer diagnosis and simultaneous in situ therapy. However, some drawbacks remain for traditional organic photosensitizers, such as poor photostability, short excitation wavelength, and shallow penetration depth, which will greatly lower the chemotherapy treatment efficiency. Herein, we present lipid-encapsulated two-photon active aggregation-induced emission (AIE) luminogen and paclitaxel (PTX) nanoparticles (AIE@PTX NPs) with bright red fluorescence emission, excellent photostability, and good biocompatibility. The AIE@PTX NPs exhibit dual functionality as two-photon probes for visualizing blood vessels and tumor structures, achieving penetration depth up to 186 and 120 µm, respectively. Furthermore, the tumor growth of the HeLa-xenograft model can be effectively prohibited after the fluorescence imaging-guided and PTX-induced chemotherapy, which shows great potential in the clinical application of two-photon cell and tumor fluorescence imaging and cancer treatment.

Theranostic antibacterial hydrogel based on biopolymers cross-linked and doped with phytic acid from rice bran for wound healing.

Theranostic antibacterial wound dressing is highly recommended in practical applications. The conventional methods of integrating diagnostic and therapeutic functions have the disadvantages of complicated preparation, mutual interference, inability to effectively broad spectrum antibacterial property, and easy to induce drug-resistant bacteria. Herein, a pH and light-responsive theranostic antibacterial hydrogel is developed by biopolymers polyvinyl alcohol (PVA) and polyaniline (PANI), and cross-linking with phytic acid (PA), which is widely present in rice bran. The biological polymer-based conductive hydrogel enables timely diagnosis and photothermal sterilization in-situ for wound healing. Because PANI is highly sensitive to pH changes in the bacterial microenvironment, the hydrogel can detect bacterial infections at concentrations as low as 103 CFU/mL. Subsequently, PANI absorbs near-infrared light to achieve on-demand exothermic sterilization (under 808 nm irradiation for 20 min, the killing ratios for Staphylococcus aureus and Escherichia coli reached almost 100 %). In addition, the hydrogel can monitor the intensity of joint movement to avoid wound re-tearing sensitively. In vitro cytotoxicity and hemocompatibility experiments and in vivo full-thickness infected wound model indicate that the hydrogel has good biocompatibility, antibacterial ability, and can accelerate the wound healing effectively. This work will promote the development of wearable electronic devices and precision medicine.

Tumor Microenvironment-Activatable Phototheranostic: Leveraging Nitric Oxide and Weak Acidity as Dual Biomarkers for Ratiometric Fluorescence, Photoacoustic Imaging, and Photothermal Therapy.

Tumor microenvironment-responsive phototheranostic agents are highly sought after for their ability to improve diagnostic accuracy and treatment specificity. Here, we introduce a novel single-molecule probe, POZ-NO, which is activated by nitric oxide (NO) and weak acidity, enabling dual-mode imaging and photothermal therapy (PTT) of tumors. In acidic environments with elevated NO levels, POZ-NO exhibits a distinctive ratiometric fluorescence signal shift from the red to near-infrared, accompanied by a 700 nm photoacoustic signal. Additionally, POZ-NO demonstrated potent photothermal effects upon NO and acidity activation, achieving an impressive conversion efficiency of 74.3% under 735 nm laser irradiation. In vivo studies confirm POZ-NO's ability to accurately image tumors through ratiometric fluorescence and photoacoustic modes while selectively treating tumors with PTT.

Targeted Nanotheransotics: Integration of Preclinical MRI and CT in the Molecular Imaging and Therapy of Advanced Diseases.

The integration of preclinical magnetic resonance imaging (MRI) and computed tomography (CT) methods has significantly enhanced the area of therapy and imaging of targeted nanomedicine. Nanotheranostics, which make use of nanoparticles, are a significant advancement in MRI and CT imaging. In addition to giving high-resolution anatomical features and functional information simultaneously, these multifunctional agents improve contrast when used. In addition to enabling early disease detection, precise localization, and personalised therapy monitoring, they also enable early disease detection. Fusion of MRI and CT enables precise in vivo tracking of drug-loaded nanoparticles. MRI, which provides real-time monitoring of nanoparticle distribution, accumulation, and release at the cellular and tissue levels, can be used to assess the efficacy of drug delivery systems. The precise localization of nanoparticles within the body is achievable through the use of CT imaging. This technique enhances the capabilities of MRI by providing high-resolution anatomical information. CT also allows for quantitative measurements of nanoparticle concentration, which is essential for evaluating the pharmacokinetics and biodistribution of nanomedicine. In this article, we emphasize the integration of preclinical MRI and CT into molecular imaging and therapy for advanced diseases.

Recent advances in cell membrane camouflaged nanotherapeutics for the treatment of bacterial infection.

Infectious diseases caused by bacterial infections are common in clinical practice. Cell membrane coating nanotechnology represents a pioneering approach for the delivery of therapeutic agents without being cleared by the immune system in the meantime. And the mechanism of infection treatment should be divided into two parts: suppression of pathogenic bacteria and suppression of excessive immune response. The membrane-coated nanoparticles exert anti-bacterial function by neutralizing exotoxins and endotoxins, and some other bacterial proteins. Inflammation, the second procedure of bacterial infection, can also be suppressed through targeting the inflamed site, neutralization of toxins, and the suppression of pro-inflammatory cytokines. And platelet membrane can affect the complement process to suppress inflammation. Membrane-coated nanoparticles treat bacterial infections through the combined action of membranes and nanoparticles, and diagnose by imaging, forming a theranostic system. Several strategies have been discovered to enhance the anti-bacterial/anti-inflammatory capability, such as synthesizing the material through electroporation, pretreating with the corresponding pathogen, membrane hybridization, or incorporating with genetic modification, lipid insertion, and click chemistry. Here we aim to provide a comprehensive overview of the current knowledge regarding the application of membrane-coated nanoparticles in preventing bacterial infections as well as addressing existing uncertainties and misconceptions.

Near-infrared Light-Triggered Size-Shrinkable theranostic nanomicelles for effective tumor targeting and regression.

Most nanomedicines with suitable sizes (normally 100-200 nm) exhibit favorable accumulation in the periphery of tumors but hardly penetrate into deep tumors. Effective penetration of nanomedicines requires smaller sizes (less than 30 nm) to overcome the elevated tumor interstitial fluid pressure. Moreover, integrating an efficient diagnostic agent in the nanomedicines is in high demand for precision theranostics of tumors. To this end, a near-infrared light (NIR) -triggered size-shrinkable micelle system (Fe3O4@AuNFs/DOX-M) coloaded antitumor drug doxorubicin (DOX) and biomodal imaging agent magnetic gold nanoflower (Fe3O4@AuNFs) was developed to achieve efficient theranostic of tumors. Upon the accumulation of Fe3O4@AuNFs/DOX-M in the tumor periphery, a NIR laser was irradiated near the tumor sites, and the loaded Fe3O4@Au NFs could convert the light energy to heat, which triggered the cleavage of DOX-M to the ultra-small micelles (∼5 nm), thus realizing the deep penetration of micelles and on-demand drug release. Moreover, Fe3O4@AuNFs in the micelles could also be used as CT/MRI dual-modal contrast agent to "visualize" the tumor. Up to 92.6 % of tumor inhibition was achieved for the developed Fe3O4@AuNFs/DOX-M under NIR irradiation. This versatile micelle system provided a promising drug carrier platform realizing efficient tumor dual-modal diagnosis and photothermal-chemotherapy integration.

Tumor versus Tumor Cell Targeting in Metal-Based Nanoparticles for Cancer Theranostics.

The application of metal-based nanoparticles (mNPs) in cancer therapy and diagnostics (theranostics) has been a hot research topic since the early days of nanotechnology, becoming even more relevant in recent years. However, the clinical translation of this technology has been notably poor, with one of the main reasons being a lack of understanding of the disease and conceptual errors in the design of mNPs. Strikingly, throughout the reported studies to date on in vivo experiments, the concepts of "tumor targeting" and "tumor cell targeting" are often intertwined, particularly in the context of active targeting. These misconceptions may lead to design flaws, resulting in failed theranostic strategies. In the context of mNPs, tumor targeting can be described as the process by which mNPs reach the tumor mass (as a tissue), while tumor cell targeting refers to the specific interaction of mNPs with tumor cells once they have reached the tumor tissue. In this review, we conduct a critical analysis of key challenges that must be addressed for the successful targeting of either tumor tissue or cancer cells within the tumor tissue. Additionally, we explore essential features necessary for the smart design of theranostic mNPs, where 'smart design' refers to the process involving advanced consideration of the physicochemical features of the mNPs, targeting motifs, and physiological barriers that must be overcome for successful tumor targeting and/or tumor cell targeting.