Development Of Nanomedicines Research Articles

A Patent Analysis on Nano Drug Delivery Systems.

A nano drug delivery system is an effective tool for drug delivery and controlled release, which is used for a variety of medical applications. In recent decades, nano drug delivery systems have been significantly developed with the emergence of new nanomaterials and nanotechnologies. This article aimed to provide insight into the technological development of nano drug delivery systems through patent analysis. 3708 patent documents were used for patent analysis after retrieval from the Incopat patent database. The number of patents on nano drug delivery systems has shown a rapid growth trend in the past two decades. At present, China and the United States have obvious contributions to the number of patents. According to the patent data, the nanomaterials used in nano drug delivery system are mainly inorganic nanomaterials, lipid-based nanomaterials, and macromolecules. In recent years, the highly cited patents (≥14) for nano drug delivery systems mainly involve lipid-based nanomaterials, indicating that their technology is mature and widely used. The inorganic nanomaterials in drug delivery have received increasing attention, and the number of related patents has increased significantly after 2016. The number of highly cited patents in the United States is 250, which is much higher than in other countries. Even after decades of development, nano drug delivery systems remain a hot topic for researchers. The significant increase in patents since 2016 can be attributed to the large number of new patents from China. However, according to the proportion of highly cited patents in total, China's patented technologies in nano drug delivery systems are not advanced enough compared to developed countries, including the United States, Canada, Germany, and France. In the future, research on emerging nanomaterials for nano drug delivery systems, such as inorganic nanomaterials, may focus on developing new materials and optimising their properties. The lipid-based and polymer- based nanomaterials can be continuously improved for the development of new nanomedicines.

Advances in Drug Delivery Systems for the Treatment of Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a common and catastrophic hematological neoplasm with high mortality rates. Conventional therapies, including chemotherapy, hematopoietic stem cell transplantation (HSCT), immune therapy, and targeted agents, have unsatisfactory outcomes for AML patients due to drug toxicity, off-target effects, drug resistance, drug side effects, and AML relapse and refractoriness. These intrinsic limitations of current treatments have promoted the development and application of nanomedicine for more effective and safer leukemia therapy. In this review, the classification of nanoparticles applied in AML therapy, including liposomes, polymersomes, micelles, dendrimers, and inorganic nanoparticles, is reviewed. In addition, various strategies for enhancing therapeutic targetability in nanomedicine, including the use of conjugating ligands, biomimetic-nanotechnology, and bone marrow targeting, which indicates the potential to reverse drug resistance, are discussed. The application of nanomedicine for assisting immunotherapy is also involved. Finally, the advantages and possible challenges of nanomedicine for the transition from the preclinical phase to the clinical phase are discussed.

Multi‐synergistic chemotherapeutic drug assemblies to activate colorectal cancer immunotherapy by modulating the multilevel immunosuppressive characteristics

AbstractThe life‐threatening colorectal cancer exhibits multilevel immunosuppressive characteristics, including low immunogenicity, abnormal cellular metabolism, and acidic immunosuppressive microenvironment. In this work, multi‐synergistic chemotherapeutic drug assemblies are fabricated to activate colorectal cancer immunotherapy by modulating the multilevel immunosuppressive characteristics. Without any drug excipients, the glycolysis inhibitor of lonidamine (LON), indoleamine 2,3‐dioxygenase 1 (IDO‐1) inhibitor of NLG919 (NLG), and the photosensitizer of chlorine e6 could self‐assemble into drug assemblies (LNC) with uniform nano‐size distribution and increased drug stability. Moreover, LNC could also promote cellular uptake and enhance drug penetration to enable efficient drug co‐delivery. Especially, the photodynamic therapy (PDT) of LNC could disrupt tumor cells to release tumor‐associated antigens, thus efficiently suppressing primary tumor growth and improving tumor immunogenicity. Meanwhile, LNC could also reduce the activity of IDO‐1 and attenuate the glycolysis metabolism, thereby reversing the multilevel immunosuppressive characteristics to promote T cell activation. Benefiting from the multi‐synergistic effects, LNC efficiently eradicates the primary tumor growth and also activates systemic antitumor immunity for metastatic tumor inhibition. Such a simple formulation but a multi‐synergistic strategy may accelerate the development of translational nanomedicine for colorectal cancer immunotherapy by using small molecular drug combinations.

Self-enhanced targeted nanomedicines based on iron starvation acclimation for tumor-specific therapy

Transferrin receptors (TfR)-targeted drug is a promising candidate for clinical tumor-targeted therapy due to the overexpressed TfR on the tumor-cell membrane. However, the variation of TfR expression levels in different tumor types seriously challenged the therapeutic effect of TfR-targeted drugs, hindering their development and clinical translation. In this work, we designed a novel TfR-targeted nanomedicine (DFO@lipo-Tf NPs) with self-enhanced targeting ability by up-regulating the expression of TfR on tumors through iron starvation acclimation, which significantly improves the drug accumulation in the tumor. The self-enhanced targeted nanoparticles (DFO@lipo-Tf NPs) were constructed by encapsulating deferoxamine (DFO) in transferrin (Tf) modified liposome. DFO has been proven to scavenge Fe3+ in the acid tumor environment, which can lead to iron starvation in tumor cells and further induce the increase of TfR expression. We then encapsulated the chemotherapeutic drug doxorubicin (DOX) into DFO@lipo-Tf NPs to form self-enhanced targeted chemotherapeutic nanomedicine (DFO/DOX@lipo-Tf NPs), which dramatically increase in vitro and in vivo therapeutic effect to HeLa cell-line tumor with inherently low TfR expression. This conceptual strategy provides an innovative design for advanced TfR-targeted nanomedicine by breaking through the bottleneck of targeting efficiency in tumor-targeted therapy, laying a foundation for future development of TfR-targeted nanomedicines.

Emerging Perspectives on Prime Editor Delivery to the Brain.

Prime editing shows potential as a precision genome editing technology, as well as the potential to advance the development of next-generation nanomedicine for addressing neurological disorders. However, turning in prime editors (PEs), which are macromolecular complexes composed of CRISPR/Cas9 nickase fused with a reverse transcriptase and a prime editing guide RNA (pegRNA), to the brain remains a considerable challenge due to physiological obstacles, including the blood-brain barrier (BBB). This review article offers an up-to-date overview and perspective on the latest technologies and strategies for the precision delivery of PEs to the brain and passage through blood barriers. Furthermore, it delves into the scientific significance and possible therapeutic applications of prime editing in conditions related to neurological diseases. It is targeted at clinicians and clinical researchers working on advancing precision nanomedicine for neuropathologies.

Self-Assembled PD-L1 Downregulator to Boost Photodynamic Activated Tumor Immunotherapy Through CDK5 Inhibition.

The immunosuppressive characteristics and acquired immune resistance can restrain the therapy-initiated anti-tumor immunity. In this work, an antibody free programmed death receptor ligand 1 (PD-L1) downregulator (designated as CeSe) is fabricated to boost photodynamic activated immunotherapy through cyclin-dependent kinase 5 (CDK5) inhibition. Among which, FDA approved photosensitizer of chlorin e6 (Ce6) and preclinical available CDK5 inhibitor of seliciclib (Se) are utilized to prepare the nanomedicine of CeSe through self-assembly technique without drug excipient. Nanoscale CeSe exhibits an increased stability and drug delivery efficiency, contributing to intracellular production of reactive oxygen species (ROS) for robust photodynamic therapy (PDT). The PDT of CeSe can not only suppress the primary tumor growth, but also induce the immunogenic cell death (ICD) to release tumor associated antigens. More importantly, the CDK5 inhibition by CeSe can downregulate PD-L1 to re-activate the systemic anti-tumor immunity by decreasing the tumor immune escape and therapy-induced acquired immune resistance. This work provides an antibody free strategy to activate systemic immune response for metastatic tumor treatment, which may accelerate the development of translational nanomedicine with sophisticated mechanism.

Reactive oxygen species-responsive nanotherapy for the prevention and treatment of cerebral ischemia–reperfusion injury

Vascular recanalization intervention is the primary recommended approach for the treatment of ischemic stroke. However, the damage caused by cerebral ischemia-reperfusion (I/R) poses a significant challenge for effective treatment. The aim of this study was to address this challenge by developing multifunctional nanoparticles (NPs). Cu4.6O NP was encapsulated by zein-Se-Se-DHA (Dz), the diselenide bond-conjugated zein and docosahexaenoic acid (DHA), and then coated by platelet membrane (PLTM) to form Cu4.6O@Dz@PLTM (MDzCu) NP. MDzCu with the PLTM coating showed strong targeting ability to the cerebral ischemic lesions in the rat model of cerebral I/R injury. Furthermore, in the reactive oxygen species (ROS)-rich brain microenvironment, both Cu4.6O and DHA are released from MDzCu, exerting ROS scavenging, promoting microglia polarization, and providing neuroprotective effects, ultimately alleviating cerebral I/R injury. This study presents several novel findings, such as the use of Cu0/Cu+ NPs for brain-related diseases, ROS scavenger-assisted DHA therapy for the central nervous system (CNS), and the application of stimuli-responsive NPs with diselenides to treat I/R injuries. This study provides insights into the development of stimuli-responsive nanomedicines with cell membrane coatings for the targeted treatment of brain diseases.

The artificial intelligence and design of experiment assisted in the development of progesterone-loaded solid-lipid nanoparticles for transdermal drug delivery

The application of Artificial Intelligence (AI) has the potential to revolutionize the formulation development of nanomedicine. This study investigated the physicochemical characteristics of progesterone-loaded solid-lipid nanoparticles (PG-SLNs) produced through an emulsification–ultrasonication process, with a focus on demonstrating the efficacy of this controlled preparation method via the Design of Experiments (DoE) and Artificial Neural Networks (ANN). Critical quality factors, including stearic acid, medium chain triglycerides (MCT), Pluronic F-127, and the amount of propylene glycol (PG), were explored using DoE to streamline experimental setups. The concentration of stearic acid was identified as a crucial factor influencing PG-SLN physicochemical properties, impacting particle size (PS), polydispersity index (PDI), zeta potential (ZP), and %drug loading (%DL). Optimal conditions for PS, PDI, ZP, and %DL were identified. DoE revealed acceptable values across multiple runs, and the ANN model demonstrates high prediction accuracy, surpassing Response Surface Methodology (RSM). The selected PG-SLN formulation was tested for transdermal drug delivery, showing improved permeation compared to PG suspension. Loading with limonene further enhances transdermal drug delivery, attributed to limonene’s role as a penetration enhancer. Moreover, the selected PG-SLN formulation was found to be safe and non-toxic to neuronal cells. The combination of DoE and ANN was proposed to enhance predictive ability. This research highlights the potential of PG-SLNs in transdermal drug delivery, emphasizing the role of limonene as a safe and effective enhancer. The study contributes to the growing interest in applying AI tools in pharmaceutical and biomedical fields for improved predictive modeling.

Facile Generation of Heterotelechelic Poly(2‐Oxazoline)s Towards Accelerated Exploration of Poly(2‐Oxazoline)‐Based Nanomedicine

AbstractControlling the end‐groups of biocompatible polymers is crucial for enabling polymer‐based therapeutics and nanomedicine. Typically, end‐group diversification is a challenging and time‐consuming endeavor, especially for polymers prepared via ionic polymerization mechanisms with limited functional group tolerance. In this study, we present a facile end‐group diversification approach for poly(2‐oxazoline)s (POx), enabling quick and reliable production of heterotelechelic polymers to facilitate POxylation. The approach relies on the careful tuning of reaction parameters to establish differential reactivity of a pentafluorobenzyl initiator fragment and the living oxazolinium chain‐end, allowing the selective introduction of N‐, S‐, O‐nucleophiles via the termination of the polymerization, and a consecutive nucleophilic para‐fluoro substitution. The value of this approach for the accelerated development of nanomedicine is demonstrated through the synthesis of well‐defined lipid‐polymer conjugates and POx‐polypeptide block‐copolymers, which are well‐suited for drug and gene delivery. Furthermore, we investigated the application of a lipid‐POx conjugate for the formulation and delivery of mRNA‐loaded lipid nanoparticles for immunization against the SARS‐COV‐2 virus, underscoring the value of POx as a biocompatible polymer platform.

Facile Generation of Heterotelechelic Poly(2-Oxazoline)s Towards Accelerated Exploration of Poly(2-Oxazoline)-Based Nanomedicine.

Controlling the end-groups of biocompatible polymers is crucial for enabling polymer-based therapeutics and nanomedicine. Typically, end-group diversification is a challenging and time-consuming endeavor, especially for polymers prepared via ionic polymerization mechanisms with limited functional group tolerance. In this study, we present a facile end-group diversification approach for poly(2-oxazoline)s (POx), enabling quick and reliable production of heterotelechelic polymers to facilitate POxylation. The approach relies on the careful tuning of reaction parameters to establish differential reactivity of a pentafluorobenzyl initiator fragment and the living oxazolinium chain-end, allowing the selective introduction of N-, S-, O-nucleophiles via the termination of the polymerization, and a consecutive nucleophilic para-fluoro substitution. The value of this approach for the accelerated development of nanomedicine is demonstrated through the synthesis of well-defined lipid-polymer conjugates and POx-polypeptide block-copolymers, which are well-suited for drug and gene delivery. Furthermore, we investigated the application of a lipid-POx conjugate for the formulation and delivery of mRNA-loaded lipid nanoparticles for immunization against the SARS-COV-2 virus, underscoring the value of POx as a biocompatible polymer platform.

Apoptosis‐Sensitizing Tumor Nanomedicine by Regulating Pyroptosis‐Associated Inflammatory Cell Death

AbstractThe vigorous development of cancer nanomedicine has revolutionized traditional oncology medicine, but it is also limited by the continuous mutation of cunning cancer cells, leading to apoptosis insensitivity and therapeutic disappointment. Inflammatory‐regulated cell death (RCD), especially pyroptosis‐related cell death, demonstrates huge potential for apoptosis sensitization due to its unique biochemical characteristics. The aim of this research is to present a thorough synopsis of the current knowledge on pyroptosis‐associated inflammatory cell death, including pyroptosis, cuproptosis, and PANoptosis, and the synergistic function in cancer nano therapy. Paradigm studies of pyroptosis‐related cell death‐mediated apoptosis‐sensitizing tumor nanotherapeutics are introduced in detail, and the coordination mechanisms based on nanomaterials are also discussed. In addition, multi‐angle analysis of the future prospects of pyroptosis‐sensitized tumor nanomedicine based on various nanomaterials is also emphasized to further expand the application scope of inflammatory RCD. It is believed that emerging auxiliary apoptosis‐sensitizing treatments based on inflammatory RCD will greatly promote the progress of cancer nanomedicine.

Nanoparticle-Mediated Drug Delivery Systems for Precision Targeting in Oncology.

Nanotechnology has emerged as a transformative force in oncology, facilitating advancements in site-specific cancer therapy and personalized oncomedicine. The development of nanomedicines explicitly targeted to cancer cells represents a pivotal breakthrough, allowing the development of precise interventions. These cancer-cell-targeted nanomedicines operate within the intricate milieu of the tumour microenvironment, further enhancing their therapeutic efficacy. This comprehensive review provides a contemporary perspective on precision cancer medicine and underscores the critical role of nanotechnology in advancing site-specific cancer therapy and personalized oncomedicine. It explores the categorization of nanoparticle types, distinguishing between organic and inorganic variants, and examines their significance in the targeted delivery of anticancer drugs. Current insights into the strategies for developing actively targeted nanomedicines across various cancer types are also provided, thus addressing relevant challenges associated with drug delivery barriers. Promising future directions in personalized cancer nanomedicine approaches are delivered, emphasising the imperative for continued optimization of nanocarriers in precision cancer medicine. The discussion underscores translational research's need to enhance cancer patients' outcomes by refining nanocarrier technologies in nanotechnology-driven, site-specific cancer therapy.

Efficient Strategy to Synthesize Tunable pH-Responsive Hybrid Micelles Based on Iron Oxide and Gold Nanoparticles.

The preparation of multifunctional nanomaterials based on inorganic nanoparticles with organic materials has emerged as a promising strategy for the development of new nanomedicines for in vitro and in vivo biomedical applications. Here, we synthesized pH-responsive hybrid inorganic micelles by combining a novel pH-responsive amphiphilic molecule with hydrophobic payloads. This amphiphile was synthesized in a one-pot reaction and self-assembled readily into micelles under acidic pH conditions. In the presence of hydrophobic NP payloads such as AuNPs or IONPs, the amphiphile self-organized around them through hydrophobic interactions, resulting in the formation of colloidally stable hybrid micelles. The size of the hydrophobic NPs determined the pH-response of the inorganic hybrid micelles, which is tuned from pH 7 to 11 for our pH-responsive amphiphilic molecule. This achievement represents a novel approach for the synthesis of tunable pH-responsive hybrid micelles based on inorganic NPs for biomedical imaging, hyperthermia treatment, and also drug delivery nanosystems.

EGCG-vanadium nanomedicine with neutral pH Fenton reaction activity inhibits heat shock proteins for enhanced photothermal/chemodynamic therapy

A burgeoning interest has recently focused on the development of nanomedicine to integrate noninvasive photothermal therapy (PTT) and chemodynamic therapy (CDT) for synergistic tumor treatments, owing to PTT's amplification effect on CDT. However, challenges emerge as hyperthermia often induces an unwarranted overexpression of cytoprotective heat shock proteins (HSPs), thereby curtailing PTT efficacy. Additionally, the nearly neutral tumor intracellular pH (pHi ≈ 7.2) that handicaps the Fenton reaction poses a leading limitation to CDT. Addressing these hurdles, we introduce EVP, a nanomedicine developed through the straightforward assembly of epigallocatechin gallate (EGCG), vanadium sulfate (VOSO4), and Pluronic F-127 (PF127). EVP comprehensively downregulates overexpressed HSPs (HSP 60, 70, 90) through the collaborative action of EGCG and vanadyl (VO2+). Moreover, the tumor intracellular pH-processed Fenton-like reaction by VO2+ ensures highly efficient hydroxyl radicals (OH) production in cytosols, overcoming the stringent acidity requirement for CDT. Additionally, the hyperthermia induced by PTT augments OH production, further enhancing CDT efficacy. In vitro and in vivo experiments validate EVP's excellent biocompatibility and potent tumor inhibition, highlighting its substantial potential in tumor therapy.

Antibacterial and Wound Healing Efficacy of Silver Nanoparticles Synthesized from Root Bark of Berberis lycium Royle

AbstractInfectious diseases are becoming a worldwide threat due to antibiotic resistance. Therefore, it is necessary to prepare innovative antibiotics against bactericidal activities. The development of nanomedicine has been greatly aided by nanotechnology. A focal point of exploration involves the production of noble metal nanoparticles, owing to their diverse applications. The study's subjects are the synthesis, characterization, and assessment of silver nanoparticles (AgNPs) derived from Berberis lyceum Royle root bark (BLR) extract. The study revealed the potent antibacterial properties of BLR‐AgNPs, with heightened efficacy against S. pyogenes (16.7±0.3 mm) and comparatively lower activity against E. coli (1.1±0.1 mm). Minimum inhibitory concentration assessment indicated maximum activity at 10 μg/mL, whereas 2.5 μg/mL demonstrated the least inhibitory effect. Furthermore, the wound healing potential of BLR‐AgNPs was explored, demonstrating superior activity (0.19±0.02 cm) equated to BLR‐extract (0.46±0.02 cm) and untreated wounds (0.77±0.02 cm). These findings underscore the considerable antibacterial and wound‐healing capabilities of BLR‐AgNPs.

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.

Engineering Cu nanoclusters with aggregation-induced emission for photodynamic healing of wound with drug-resistant bacteria-infection

Efforts to expedite the development of novel antimicrobial agents without drug resistance are imperative to combat drug-resistant bacterial infections. In this study, Cu nanoclusters (NCs) with aggregation-induced emission (AIE) were designed by manipulating the pH to control the aggregation of Cu(I) complexes on the surface of a Cu(0) core. The resulting Cu NCs exhibited excellent photodynamic antimicrobial activity against a wide range of bacteria, particularly methicillin-resistant Staphylococcus aureus (MRSA), through a synergistic interplay of intrinsic and photodynamic antimicrobial mechanisms. This was achieved by the copious generation of reactive oxygen species (ROS) that are lethal to bacteria. In addition to that, these Cu NCs displayed minimal cytotoxicity and excellent biocompatibility, enabling the promoted healing of MRSA-infected wounds in mice through eliminating bacterial infection, and alleviating inflammation without causing systemic harm or impairing blood and liver functions. This study represents the first successful development of AIE-featured Cu NCs-based photodynamic antimicrobials, which may shed light on the design of other AIE-featured metal NCs, contribute to a better understanding of NC’s luminescence fundamentals, and add fuels to the development of metal NCs-based nanomedicine.

Dual regulation of the orderly aggregation of covalent organic frameworks at the molecular level and nanoscale to achieve efficient phototherapy and gene therapy

Numerous studies have established the promise of combining phototherapy and gene therapy. However, there are persistent obstacles hindering the full optimization of this combined therapeutic approach, such as the maximum development of photosensitizers and the construction of high-performance gene carriers. The LEGO stacking characteristics of COFs have brought infinite imagination to the construction of delivery systems, allowing for the design of responsive nano castles based on different application scenarios. Here, we have constructed a novel cationic multifunctional nano COF nucleic acid delivery system based on photosensitizer and cationic monomers. The long-range ordered structure of COF effectively regulates the spatial distribution of photosensitizer, thereby preserving their phototherapy efficacy. Simultaneously, the inherent cationic porous nanostructure equips COF with exceptional capabilities for delivering nucleic acids. This integrated multifunctional nano delivery system significantly enhances the combined efficacy of phototherapy and gene therapy. The phototherapy capacity of COF enables precise tumor elimination in a spatiotemporal manner, inducing robust ICD and activating immune cells at the tumor site. Furthermore, loaded siPD-L1 significantly enhances immune cell recognition and killing of tumor cells, effectively shielding mice from re-invasion and tumor metastasis. The development of multifunctional nanomedicine based on COF provides new ideas for efficient tumor combination therapy.

Gold Nanorod-Loaded Nano-Contrast Agent with Composite Shell-Core Structure for Ultrasonic/Photothermal Imaging-Guided Therapy in Ischemic Muscle Disorders.

This study aims to broaden the application of nano-contrast agents (NCAs) within the realm of the musculoskeletal system. It aims to introduce novel methods, strategies, and insights for the clinical management of ischemic muscle disorders, encompassing diagnosis, monitoring, evaluation, and therapeutic intervention. We developed a composite encapsulation technique employing O-carboxymethyl chitosan (OCMC) and liposome to encapsulate NCA-containing gold nanorods (GNRs) and perfluoropentane (PFP). This nanoscale contrast agent was thoroughly characterized for its basic physicochemical properties and performance. Its capabilities for in vivo and in vitro ultrasound imaging and photothermal imaging were authenticated, alongside a comprehensive biocompatibility assessment to ascertain its effects on microcirculatory perfusion in skeletal muscle using a murine model of hindlimb ischemia, and its potential to augment blood flow and facilitate recovery. The engineered GNR@OCMC-liposome/PFP nanostructure exhibited an average size of 203.18±1.49 nm, characterized by size uniformity, regular morphology, and a good biocompatibility profile. In vitro assessments revealed NCA's potent photothermal response and its transformation into microbubbles (MBs) under near-infrared (NIR) irradiation, thereby enhancing ultrasonographic visibility. Animal studies demonstrated the nanostructure's efficacy in photothermal imaging at ischemic loci in mouse hindlimbs, where NIR irradiation induced rapid temperature increases and significantly increased blood circulation. The dual-modal ultrasound/photothermal NCA, encapsulating GNR and PFP within a composite shell-core architecture, was synthesized successfully. It demonstrated exceptional stability, biocompatibility, and phase transition efficiency. Importantly, it facilitates the encapsulation of PFP, enabling both enhanced ultrasound imaging and photothermal imaging following NIR light exposure. This advancement provides a critical step towards the integrated diagnosis and treatment of ischemic muscle diseases, signifying a pivotal development in nanomedicine for musculoskeletal therapeutics.

Selective binding of cationic fibrinogen-mimicking chitosan nanoparticles to activated platelets and efficient drug release for antithrombotic therapy

Thrombosis is the main cause of catastrophic events including ischemic stroke, myocardial infarction and pulmonary embolism. Acetylsalicylic acid (ASA) therapy offers a desirable approach to antithrombosis through a reduction of platelet reactivity. However, major bleeding complications, severe off-target side effects, and resistance or nonresponse to ASA greatly attenuate its clinical outcomes. Herein, we report a cationic fibrinogen-mimicking nanoparticle, denoted as ASA-RGD-CS@TPP, to achieve activated-platelet-targeted delivery and efficient release of ASA for safer and more effective antithrombotic therapy. This biomimetic antithrombotic system was prepared by one-pot ionic gelation between cationic arginine-glycine-aspartic acid (RGD)-grafted chitosan (RGD-CS) and anionic tripolyphosphate (TPP). The platform exhibited selective binding to activated platelets, leading to efficient release of ASA and subsequent attenuation of platelet functions, including the remarkable inhibition of platelet aggregation through a potent blockage of cyclooxygenase-1 (COX-1). After intravenous administration, ASA-RGD-CS@TPP displayed significantly prolonged circulation time and successful prevention of thrombosis in a mouse model. ASA-RGD-CS@TPP was demonstrated to significantly enhance antithrombotic therapy while showing minimal coagulation and hemorrhagic risks and excellent biocompatibility in vivo as compared to free ASA. This platform provides a simple, safe, effective and targeted strategy for the development of antithrombotic nanomedicines.