Fluorescence imaging-guided surgery: current status and future directions.

Surgery is one of the most important paradigms for tumor therapy, while fluorescence imaging (FI) offers real-time intraoperative guidance, greatly boosting treatment prognosis. The imaging fidelity heavily relies on not only imaging facilities but also probes for imaging-guided surgery (IGS). So far, a great number of IGS probes with emission in visible (400-700 nm) and near-infrared (NIR 700-1700 nm) windows have been developed for pinpointing disease margins intraoperatively. Herein, the state-of-the-art fluorescent probes for IGS are timely updated, with a special focus on the fluorescent probes under clinical examination. For a better demonstration of the superiority of NIR FI over visible FI, both imaging modalities are critically compared regarding signal-to-background ratio, penetration depth, resolution, tissue autofluorescence, photostability, and biocompatibility. Various types of fluorescence IGS have been summarized to demonstrate its importance in the medical field. Furthermore, the most recent progress of fluorescent probes in NIR-I and NIR-II windows is summarized. Finally, an outlook on multimodal imaging, FI beyond NIR-II, efficient tumor targeting, automated IGS, the use of AI and machine learning for designing fluorescent probes, and the fluorescence-guided da Vinci surgical system is given. We hope this review will stimulate interest among researchers in different areas and expedite the translation of fluorescent probes from bench to bedside.

Advancements in manganese complex-based MRI agents: Innovations, design strategies, and future directions.

This review focuses on the advancements in manganese (Mn) complex-based magnetic resonance imaging (MRI) agents for imaging different diseases. Here we emphasize the unique redox properties of Mn to deliver innovative MRI contrast agents, including small molecules, nanoparticles (NPs), metal-organic frameworks (MOFs), and polymer hybrids. Aspects of their rational design have been discussed, including size dependence, morphology tuning, surface property enhancement, etc., while also discussing the existing challenges and potential solutions. The present work will inspire and motivate scientists to emphasize MRI-guided applications and bring clinical success in the coming years.

Highly efficient piezocatalytic composite with chitosan biopolymeric membranes and bismuth ferrite nanoparticles for dye decomposition and pathogenic S. aureus bacteria killing.

Untreated wastewater harbors dangerous pathogens, chemicals, and pollutants, posing grave public health threats. Nowadays, there is a rising demand for eco-friendly technologies for wastewater treatment. Recently, piezoelectric materials-based wastewater treatment technology has captured considerable interest among researchers because of its noninvasiveness and rapidity. Herein, a highly efficient piezoelectric composite material is designed with chitosan-incorporated bismuth ferrite (BFO) nanocrystals, to decompose pollutants and ablate bacteria in wastewater. On one hand, piezoelectric BFO has shown exclusive piezo-coefficient for ultrasound-mediated reactive oxygen species (ROS) production. On the other hand, chitosan depicts its biocompatible nature, which not only promotes cellular adhesion but also significantly elevates the ROS production capabilities of BFO under ultrasound. The synergistic effect of these two piezoelectric units in one composite entity shows an improved ROS production, eradicating ∼87.8% of Rhodamine B within 80 min under soft ultrasound treatment (rate constant, k ≈ 0.02866 min-1). After performing the scavenger experiment, it has been found that hydroxyl radicals are the dominating factor in this case. Further, the reusability of the composite piezocatalyst is confirmed through multiple cycles (five times) of the same experiment. The high polarizability of the composite material facilitates the generation of piezoelectric power through finger tapping (∼12.05 V), producing substantial instantaneous piezo-voltage. Moreover, the sample exhibits remarkable antibacterial activity, with nearly 99% bacterial eradication within 30 min. This indicates a significant advancement in utilizing biopolymeric composites incorporated with BFO for fabricating versatile devices with multidimensional applications.

NIR-II Fluorescent Probes for Fluorescence-Imaging-Guided Tumor Surgery.

Second near-infrared (NIR-II) fluorescence imaging is the most advanced imaging fidelity method with extraordinary penetration depth, signal-to-background ratio, biocompatibility, and targeting ability. It is currently booming in the medical realm to diagnose tumors and is being widely applied for fluorescence-imaging-guided tumor surgery. To efficiently execute this modern imaging modality, scientists have designed various probes capable of showing fluorescence in the NIR-II window. Here, we update the state-of-the-art NIR-II fluorescent probes in the most recent literature, including indocyanine green, NIR-II emissive cyanine dyes, BODIPY probes, aggregation-induced emission fluorophores, conjugated polymers, donor-acceptor-donor dyes, carbon nanotubes, and quantum dots for imaging-guided tumor surgery. Furthermore, we point out that the new materials with fluorescence in NIR-III and higher wavelength range to further optimize the imaging results in the medical realm are a new challenge for the scientific world. In general, we hope this review will serve as a handbook for researchers and students who have an interest in developing and applying fluorescent probes for NIR-II fluorescence-imaging-guided surgery and that it will expedite the clinical translation of the probes from bench to bedside.

Fabrication and Therapeutic Process of a Green Silver-Nanoparticle-Embedded Mucilage Microsphere for Pathogenic-Bacteria-Infected Second-Degree Burn and Excision Wounds.

Multidrug-resistant bacteria are a serious problem in biomedical applications that decrease the wound healing process and increase the mortality rate. Therefore, in this study, we have prepared a green-synthesized silver-nanoparticle-encapsulated mucilage microsphere (HMMS@GSNP) from Hibiscus rosa sinensis leaves and applied it to pathogen-infected burn and excision wounds. Biophysical properties like size, polydispersity index, absorbance capacity, and drug release were measured by different techniques like field-emission scanning electron microscopy, dynamic light scattering, swelling ratio, etc. The strong antibacterial activity of a HMMS@GSNP microsphere was measured by minimum inhibitory concentration assay, minimum bactericidal concentration assay, and agar well diffusion methods. The HMMS@GSNP microsphere enhanced the cell viability, cell proliferation, migration, antioxidant, and antiinflammation activity compared to untreated GSNP and HMMS, as quantified by MTT assay, BrdU assay, scratch wound assay, reactive oxygen species scavenging assay, and Western blot analysis, respectively. In the in vivo experiment, we used a methicillin-resistant Staphylococcus aureus bacteria-infected, burn-and-excision-wound-created male BALB/c mice model. The HMMS@GSNP-treated burn-and-excision-wound-infected mice showed significant results compared to other groups (untreated, Silverex Ionic Gel, AgNO3, HMMS, and GSNP), and the mice tissues were utilized for bacteria count, immunoblot analysis, histological studies, and real-time polymerase chain reaction. Thus, the HMM@GSNP microsphere is an excellent therapeutic material that can be used as a topical agent for the management of chronic wound therapy.

Breaking barriers in cancer treatment: nanobiohybrids empowered by modified bacteria and vesicles.

Cancer, the leading global cause of mortality, poses a formidable challenge for treatment. The effectiveness of cancer therapies, ranging from chemotherapy to immunotherapy, relies on the precise delivery of therapeutic agents to tumor tissues. Nanobiohybrids, resulting from the fusion of bacteria with nanomaterials, constitute a promising delivery system. Nanobiohybrids offer several advantages, including the ability to target tumors, genetic engineering capabilities, programmed product creation, and the potential for multimodal treatment. Recent advances in targeted tumor treatments have leveraged bacteria-based nanobiohybrids. Here, we outline the progress in cancer treatment using nanobiohybrids. Our focus is particularly on various therapeutic approaches within the context of nanobiohybrid systems, where bacteria are integrated with nanomaterials to combat cancer. It has been demonstrated that bacteria-based nanobiohybrids present a robust and effective method for tumor theranostics.

Natural Clay-Modified Piezocatalytic Membrane for Efficient Removal of Coliform Bacteria from Wastewater.

In the modern era, water pollution, especially from industries, agricultural farms, and residential areas, is caused by the release of a large scale of heavy metals, organic pollutants, chemicals, etc., into the environment, posing a serious threat to aquatic ecosystems and nature. Moreover, untreated sewage waste discharged directly into nearby water bodies can cause various diseases to mankind due to the high load of fecal coliform bacteria. This work demonstrates the development of a biocompatible, cost-effective, highly robust, efficient, flexible, freestanding, and reusable membrane using naturally formed biocompatible kaolinite clay-doped poly(vinylidene fluoride-hexafluoropropylene) (PVDF-HFP) for effective piezodynamic destruction of coliform bacteria. In this study, Escherichia coli (E. coli) and Enterococcus faecalis (E. faecalis) have been used to evaluate the mechanical stimulus-responsive antibacterial efficacy of the nanocomposite membrane. The membrane can effectively eradicate nearly 99% viable E. coli and 97% E. faecalis within a span of 40 min under mechanical stimulation (soft ultrasound ∼15 kHz). To further understand the mechanism, an evaluation of reactive oxygen species and bacterial FESEM was performed. These studies revealed that bacterial cells suffered severe visible cell damage after 40 min of piezocatalysis, elucidating the fact that the synthesized membrane is capable of producing a superior piezodynamic antibacterial effect.

Development of Polymethine Dyes for NIR-II Fluorescence Imaging and Therapy.

Fluorescence imaging in the second near-infrared window (NIR-II) is burgeoning because of its higher imaging fidelity in monitoring physiological and pathological processes than clinical visible/the second near-infrared window fluorescence imaging. Notably, the imaging fidelity is heavily dependent on fluorescence agents. So far, indocyanine green, one of the polymethine dyes, with good biocompatibility and renal clearance is the only dye approved by the Food and Drug Administration, but it shows relatively low NIR-II brightness. Importantly, tremendous efforts are devoted to synthesizing polymethine dyes for imaging preclinically and clinically. They have shown feasibility in the customization of structure and properties to fulfill various needs in imaging and therapy. Herein, a timely update on NIR-II polymethine dyes, with a special focus on molecular design strategies for fluorescent, photoacoustic, and multimodal imaging, is offered. Furthermore, the progress of polymethine dyes in sensing pathological biomarkers and even reporting drug release is illustrated. Moreover, the NIR-II fluorescence imaging-guided therapies with polymethine dyes are summarized regarding chemo-, photothermal, photodynamic, and multimodal approaches. In addition, artificial intelligence is pointed out for its potential to expedite dye development. This comprehensive review will inspire interest among a wide audience and offer a handbook for people with an interest in NIR-II polymethine dyes.

Facile process ofHibiscusmucilage polymer formulation usingHibiscus rosa-sinensisleaves to treat second-degree burn and excision wounds.

Mucilage is a sticky substance found in various plants and microorganisms and is made up of proteins and polysaccharides. Mucilage fromHibiscus rosa sinensisisis a complex polysaccharide traditionally used to treat different skin diseases. In our study, we fabricated mucilage polymer fromHibiscus rosa sinensisleaves and evaluated its potential application in second-degree burns and excision wounds. The physical properties of Hibiscus mucilage (HM) polymer were demonstrated by using Ultraviolet-visible absorption spectroscopy, x-ray diffraction, Fourier transform infrared spectroscopy, dynamic light scattering, Scanning electron microscopy, Brunauer-Emmett-Tellerand, Swelling ratio. The human cell lines WI-38, and HaCaT have been used forin-vitroexperiments like MTT, scratch wound, BrdU, ROS scavenging assays, and western blot analysis. The results of the MTT, scratch-wound, and BrdU assay indicated that the HM polymer is nontoxic in nature and also enhances both the properties of cellular migration and proliferation, respectively. On the other hand, the result of the ROS scavenging assay suggested that HM polymer enhances the antioxidant activity of cells while the western blot analysis designated that the HM polymer treatment caused downregulation of the pro-inflammatory cytokine IFN-γand upregulation of the pAkt (Serine 473) protein, and TGF-ß1 signaling pathway. Therefore, allin-vitroexperimental studies recommended that HM polymer is biocompatible and has antioxidant and anti-inflammatory effects. In thein vivoexperiment, second-degree burns and excision wounds were created on the dorsal surface of male BALB/c mice. After the sixth day of HM polymer treatment have developed new tissue, hair follicles, blood vessels,α-SMA, and Collagen type-1 fiber on the burn and excision wound area while the 11th day of HM polymer treatment cured the wound area significantly. Therefore, it could be contemplated that HM polymer is a potential agent for treating different wounds in the near future.

Unveiling the future: Advancements in MRI imaging for neurodegenerative disorders.

Neurodegenerative disorders represent a significant and growing global health challenge, necessitating continuous advancements in diagnostic tools for accurate and early detection. This work explores the recent progress in Magnetic Resonance Imaging (MRI) techniques and their application in the realm of neurodegenerative disorders. The introductory section provides a comprehensive overview of the study's background, significance, and objectives. Recognizing the current challenges associated with conventional MRI, the manuscript delves into advanced imaging techniques such as high-resolution structural imaging (HR-MRI), functional MRI (fMRI), diffusion tensor imaging (DTI), and positron emission tomography-MRI (PET-MRI) fusion. Each technique is critically examined regarding its potential to address theranostic limitations and contribute to a more nuanced understanding of the underlying pathology. A substantial portion of the work is dedicated to exploring the applications of advanced MRI in specific neurodegenerative disorders, including Parkinson's disease, Alzheimer's disease, Huntington's disease, and Amyotrophic Lateral Sclerosis (ALS). In addressing the future landscape, the manuscript examines technological advances, including the integration of machine learning and artificial intelligence in neuroimaging. The conclusion summarizes key findings, outlines implications for future research, and underscores the importance of these advancements in reshaping our understanding and approach to neurodegenerative disorders.

Cell membrane-coated biomimetic nanomedicines: productive cancer theranostic tools.

As the second-leading cause of human death, cancer has drawn attention in the area of biomedical research and therapy from all around the world. Certainly, the development of nanotechnology has made it possible for nanoparticles (NPs) to be used as a carrier for delivery systems in the treatment of tumors. This is a biomimetic approach established to craft remedial strategies comprising NPs cloaked with membrane obtained from various natural cells like blood cells, bacterial cells, cancer cells, etc. Here we conduct an in-depth exploration of cell membrane-coated NPs (CMNPs) and their extensive array of applications including drug delivery, vaccination, phototherapy, immunotherapy, MRI imaging, PET imaging, multimodal imaging, gene therapy and a combination of photothermal and chemotherapy. This review article provides a thorough summary of the most recent developments in the use of CMNPs for the diagnosis and treatment of cancer. It critically assesses the state of research while recognizing significant accomplishments and innovations. Additionally, it indicates ongoing problems in clinical translation and associated queries that warrant deeper research. By doing so, this study encourages creative thinking for future projects in the field of tumor therapy using CMNPs while also educating academics on the present status of CMNP research.

A state-of-the-art liposome technology for glioblastoma treatment.

Glioblastoma (GBM) is a challenging problem due to the poor BBB permeability of cancer drugs, its recurrence after the treatment, and high malignancy and is difficult to treat with the currently available therapeutic strategies. Furthermore, the prognosis and survival rate of GBM are still poor after surgical removal via conventional combination therapy. Owing to the existence of the formidable blood-brain barrier (BBB) and the aggressive, infiltrating nature of GBM growth, the diagnosis and treatment of GBM are quite challenging. Recently, liposomes and their derivatives have emerged as super cargos for the delivery of both hydrophobic and hydrophilic drugs for the treatment of glioblastoma because of their advantages, such as biocompatibility, long circulation, and ease of physical and chemical modification, which facilitate the capability of targeting specific sites, circumvention of BBB transport restrictions, and amplification of the therapeutic efficacy. Herein, we provide a timely update on the burgeoning liposome-based drug delivery systems and potential challenges in these fields for the diagnosis and treatment of brain tumors. Furthermore, we focus on the most recent liposome-based drug delivery cargos, including pH-sensitive, temperature-sensitive, and biomimetic liposomes, to enhance the multimodality in imaging and therapeutics of glioblastoma. Furthermore, we highlight the future difficulties and directions for the research and clinical translation of liposome-based drug delivery. Hopefully, this review will trigger the interest of researchers to expedite the development of liposome cargos and even their clinical translation for improving the prognosis of glioblastoma.

Piezodynamic Eradication of Both Gram-Positive and Gram-Negative Bacteria by Using a Nanoparticle Embedded Polymeric Membrane.

Nowadays, bacterial infection is regarded as a serious threat to humankind, which needs to be taken care of. The emergence of antibiotic resistance and multidrug resistance (MDR) is rendering this situation more troublesome. However, several alternative treatment regimens have aided such diseases quite well in the recent past, among which dynamic antibacterial therapies combat this situation quite well. Among various dynamic therapies, piezodynamic therapy is a very recent avenue, in which mechanical stimuli have been exploited to treat bacterial infections. Herein, piezo-active bismuth ferrite-loaded poly(vinylidene fluoride-co-hexafluoropropylene) polymer has been utilized to eradicate gram-positive bacteria (E. faecalis) and gram-negative bacteria (E. coli). The sample has been designed in a free-standing membrane form, which, under soft ultrasound (~10 kHz), generates reactive radicals to ablate bacteria. Initially, the structure and morphology of the membrane have been substantiated by using X-ray diffraction and scanning electron microscopy methods; besides, Fourier transform infrared spectrum of the sample depicts a tremendously high value of polarizability and further confirms the piezo-activity of the membrane. More than 99% of E. coli and E. faecalis have been successfully eradicated within 30 min of ultrasound. Moreover, the solid-state structure and hydrophobic nature of the membrane help us to reuse it in a cyclic manner, which is possibly reported herein for the very first time. This novel membrane could be deployed in healthcare systems and pigment industries and could be exploited as a self-cleaning material.

Contrast Agents of Magnetic Resonance Imaging and Future Perspective.

In recent times, magnetic resonance imaging (MRI) has emerged as a highly promising modality for diagnosing severe diseases. Its exceptional spatiotemporal resolution and ease of use have established it as an indispensable clinical diagnostic tool. Nevertheless, there are instances where MRI encounters challenges related to low contrast, necessitating the use of contrast agents (CAs). Significant efforts have been made by scientists to enhance the precision of observing diseased body parts by leveraging the synergistic potential of MRI in conjunction with other imaging techniques and thereby modifying the CAs. In this work, our focus is on elucidating the rational designing approach of CAs and optimizing their compatibility for multimodal imaging and other intelligent applications. Additionally, we emphasize the importance of incorporating various artificial intelligence tools, such as machine learning and deep learning, to explore the future prospects of disease diagnosis using MRI. We also address the limitations associated with these techniques and propose reasonable remedies, with the aim of advancing MRI as a cutting-edge diagnostic tool for the future.

Emerging extracellular vesicle-based carriers for glioblastoma diagnosis and therapy.

Glioblastoma (GBM) treatment is still a big clinical challenge because of its highly malignant, invasive, and lethal characteristics. After treatment with the conventional therapeutic paradigm of surgery combined with radio- and chemotherapy, patients bearing GBMs generally exhibit a poor prognosis, with high mortality and a high disability rate. The main reason is the existence of the formidable blood-brain barrier (BBB), aggressive growth, and the infiltration nature of GBMs. Especially, the BBB suppresses the delivery of imaging and therapeutic agents to lesion sites, and thus this leads to difficulties in achieving a timely diagnosis and treatment. Recent studies have demonstrated that extracellular vesicles (EVs) exhibit favorable merits including good biocompatibility, a strong drug loading capacity, long circulation time, good BBB crossing efficiency, specific targeting to lesion sites, and high efficiency in the delivery of a variety of cargos for GBM therapy. Importantly, EVs inherit physiological and pathological molecules from the source cells, which are ideal biomarkers for molecularly tracking the malignant progression of GBMs. Herein, we start by introducing the pathophysiology and physiology of GBMs, followed by presenting the biological functions of EVs in GBMs with a special focus on their role as biomarkers for GBM diagnosis and as messengers in the modulation of the GBM microenvironment. Furthermore, we provide an update on the recent progress of using EVs in biology, functionality, and isolation applications. More importantly, we systematically summarize the most recent advances of EV-based carriers for GBM therapy by delivering different drugs including gene/RNA-based drugs, chemotherapy drugs, imaging agents, and combinatory drugs. Lastly, we point out the challenges and prospects of future research on EVs for diagnosing and treating GBMs. We hope this review will stimulate interest from researchers with different backgrounds and expedite the progress of GBM treatment paradigms.

Recent progress in NIR-II fluorescence imaging-guided drug delivery for cancer theranostics.

Fluorescence imaging in the second near-infrared window (NIR-II) has become a prevalent choice owing to its appealing advantages like deep penetration depth, low autofluorescence, decent spatiotemporal resolution, and a high signal-to-background ratio. This would expedite the innovation of NIR-II imaging-guided drug delivery (IGDD) paradigms for the improvement of the prognosis of patients with tumors. This work systematically reviews the recent progress of such NIR-II IGDD-mediated cancer therapeutics and collectively brings its essence to the readers. Special care has been taken to assess their performances based on their design approach, such as enhancing their drug loading and triggering release, designing intrinsic and extrinsic fluorophores, and/ or overcoming biological barriers. Besides, the state-of-the-art NIR-II IGDD platforms for different therapies like chemo-, photodynamic, photothermal, chemodynamic, immuno-, ion channel, gas-therapies, and multiple functions such as stimulus-responsive imaging and therapy, and monitoring of drug release and therapeutic response, have been updated. In addition, for boosting theranostic outcomes and clinical translation, the innovation directions of NIR-II IGDD platforms are summarized, including renal-clearable, biodegradable, sub-cellular targeting, and/or afterglow, chemiluminescence, X-ray excitable NIR-IGDD, and even cell therapy. This review will propel new directions for safe and efficient NIR-II fluorescence-mediated anticancer drug delivery.

Topical effect of polyherbal flowers extract on xanthan gum hydrogel patch-induced wound healing activity in human cell lines and male BALB/c mice.

Wound or injury is a breakdown in the skin's protective function as well as damage to the normal tissues. Wound healing is a dynamic and complex phenomenon of replacing injured skin or body tissues. In ancient times theCalendula officinalisandHibiscus rosa-sinensisflowers were extensively used by the tribal communities as herbal medicine for various complications including wound healing. But loading and delivery of such herbal medicines are challenging because it maintains their molecular structure against temperature, moisture, and other ambient factors. This study has fabricated xanthan gum (XG) hydrogel through a facile process and encapsulatedC. officinalisandH. rosa-sinensisflower extract. The resulting hydrogel was characterized by different physical methods like x-ray diffractometer, UV-vis spectroscopy, Fourier transform infrared spectroscopy, SEM, dynamic light scattering, electronkinetic potential in colloidal systems (ZETA) potential, thermogravimetric differential thermal analysis (TGA-DTA), etc. The polyherbal extract was phytochemically screened and observed that flavonoids, alkaloids, terpenoids, tannins, saponins, anthraquinones, glycosides, amino acids, and a few percentages of reducing sugar were present in the polyherbal extract. Polyherbal extract encapsulated XG hydrogel (X@C-H) significantly enhanced the proliferation of fibroblast and keratinocyte cell lines in comparison to the bare excipient treated cells as determined by 3-(4, 5-dimethylthiazol-2-Yl)-2, 5-diphenyltetrazolium bromide assay. Also, the proliferation of these cells was confirmed by BrdU assay and enhanced expression of pAkt. In anin-vivostudy, wound healing activity of BALB/c mice was carried out and we observed that X@C-H hydrogel showed significant result compared to the other groups (untreated, X, X@C, X@H). Henceforth, we conclude that this synthesized biocompatible hydrogel could emerge as a promising carrier of more than one herbal excipients.