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Radiotherapy is a major therapeutic strategy for cancer treatment. Despite many technology advances in the last two decades, local control remains often suboptimal, especially in locally advanced tumours, which are often hypoxic, and radioresistant. In addition, irradiation of surrounding tissues and organs at risk usually precludes further dose escalation to minimize acute and late toxicities. Radiosensitizing agents such as chemotherapies targeting the DNA repair, or targeted monoclonal antibodies (cetuximab) have been shown to improve local control in many tumour types. More recently, radioenhancers have emerged as a new way to overcome the limitations of radiation. Here, we review the state of the art in this field and will focus on the past and ongoing clinical trials with the nanoparticles NBTXR3 and AGuIX®., (Copyright © 2024. Published by Elsevier Masson SAS.)

Sonodynamic therapy (SDT), featuring noninvasive, deeper penetration, low cost, and repeatability, is a promising therapy approach for deep-seated tumors. However, the general or only utilization of SDT shows low efficiency and unsatisfactory treatment outcomes due to the complicated tumor microenvironment (TME) and SDT process. To circumvent the issues, three feasible approaches for enhancing SDT-based therapeutic effects, including sonosensitizer optimization, strategies for conquering hypoxia TME, and combinational therapy are summarized, with a particular focus on the combination therapy of SDT with other therapy modalities, including chemodynamic therapy, photodynamic therapy, photothermal therapy, chemotherapy, starvation therapy, gas therapy, and immunotherapy. In the end, the current challenges in SDT-based therapy on tumors are discussed and feasible approaches for enhanced therapeutic effects are provided. It is envisioned that this review will provide new insight into the strategic design of high-efficiency sonosensitizer-derived nanotheranostics, thereby augmenting SDT and accelerating the potential clinical transformation., (© 2024 Wiley‐VCH GmbH.)

Nanomedicines have been widely used in colorectal cancer treatment, but their suboptimal targeting and deficient penetration capabilities remain obstacles in the delivery of therapeutics. In this study, inspired by the natural tumor tropism and intestinal invasion of Salmonella , we engineered highly biomimetic nanoparticles (SM-AuNRs) utilizing a Salmonella membrane to coat bacilliform Au nanorods. The engineered SM-AuNRs were able to mimic the germ's morphology and biological surface. SM-AuNRs containing the specific proteins inherited from the Salmonella membrane facilitated specific targeting and internalization into tumor cells. Meanwhile, SM-AuNRs with the rod-shaped morphology effectively traversed mucus barriers and tumor stroma. Due to the superior biological barrier penetrating and tumor targeting capabilities, doxorubicin-loaded SM-AuNRs with near-infrared laser irradiation displayed remarkable photothermal-chemotherapeutic antitumor effects in mouse orthotopic colorectal cancer models. Our findings pave the way for the design of bacteria-mimicking nanoparticles, presenting a promising avenue for the targeting and efficient treatment of colorectal cancer.

Cancer immunotherapy has demonstrated remarkable efficacy in the treatment of cancer, and it has been successfully applied in the treatment of various solid tumors. However, the response rates to immunotherapy in patients with ovarian cancer remain modest because of the immunosuppressive tumor microenvironment (TME). Tumor-associated macrophages (TAMs) represent the predominant myeloid cell population within the TME, which adopt the protumorigenic M2 phenotype and are blinded by the "don't eat me" signals from tumor cells. These characteristics of TAMs result in insufficient phagocytic activation. In this study, we constructed a SIM@TR-NP-mediated combination therapy of sonodynamic and immunotherapy. SIM@TR-NPs were modified by engineered macrophage membranes with overexpressed sialic acid-binding Ig-like lectin 10 (Siglec-10), and were internally loaded with sonosensitizer 4,4',4'',4'''-(porphine-5,10,15,20-tetrayl)tetrakis(benzoic acid) and immune adjuvant resiquimod. SIM@TR-NPs can block "don't eat me" signals to enhance macrophage phagocytosis and trigger the polarization of TAMs toward the M1 phenotype, thereby improving the immunosuppressive TME. Simultaneously, upon ultrasound irradiation, SIM@TR-NP-mediated sonodynamic therapy (SDT) triggered immunogenic cell death in tumor cells, in combination with TAM-based immunotherapy, transforming the "immune cold tumor" into an "immune hot tumor". SIM@TR-NP-mediated sonodynamic immunotherapy exhibited potent antitumor efficacy in ovarian cancer and exhibited substantial potential for improving the immunosuppressive TME. This study presents an emerging therapeutic regimen for ovarian cancer that synergizes TAM-based antitumor immunotherapy and SDT.

Inflammatory bowel disease (IBD) manifests as inflammation in the colon, rectum, and ileum, presenting a global health concern with increasing prevalence. Therefore, effective anti-inflammatory therapy stands as a promising strategy for the prevention and management of IBD. However, conventional nano drug delivery systems (NDDSs) for IBD face many challenges in targeting the intestine, such as physiological and pathological barriers, genetic variants, disease severity, and nutritional status, which often result in nonspecific tissue distribution and uncontrolled drug release. To address these limitations, stimulus-responsive NDDSs have received considerable attention in recent years due to their advantages in providing controlled release and enhanced targeting. This review provides an overview of the pathophysiological mechanisms underlying IBD and summarizes recent advancements in microenvironmental stimulus-responsive nanocarriers for IBD therapy. These carriers utilize physicochemical stimuli such as pH, reactive oxygen species, enzymes, and redox substances to deliver drugs for IBD treatment. Additionally, pivotal challenges in the future development and clinical translation of stimulus-responsive NDDSs are emphasized. By offering insights into the development and optimization of stimulus-responsive drug delivery nanoplatforms, this review aims to facilitate their application in treating IBD. STATEMENT OF SIGNIFICANCE: This review highlights recent advancements in stimulus-responsive nano drug delivery systems (NDDSs) for the treatment of inflammatory bowel disease (IBD). These innovative nanoplatforms respond to specific environmental triggers, such as pH reactive oxygen species, enzymes, and redox substances, to release drugs directly at the inflammation site. By summarizing the latest research, our work underscores the potential of these technologies to improve drug targeting and efficacy, offering new directions for IBD therapy. This review is significant as it provides a comprehensive overview for researchers and clinicians, facilitating the development of more effective treatments for IBD and other chronic inflammatory diseases., Competing Interests: Conflicts of Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

To overcome the biological barriers in the journey of systemic gene delivery, a multifaceted genomic synthetic nanomedicine was elaborated and strategically equipped with a multiple of intriguing responsiveness. Particularly, core-shell plasmid DNA condensates were created based on polyionic complexation with block copolymer of polyethylene glycol (PEG)-polylysine (PLys), namely, the nanoscaled PLys&pDNA nanoparticle tethered with the biocompatible PEG surroundings. Furthermore, redox-reversible disulfide crosslinking was introduced into PLys&pDNA nanoparticle to accomplish adequate structural stabilities, and thermal-responsive polypropylacrylamide (PNIPAM) was introduced as the secondary intermediate surroundings onto the pre-formulated PLys&pDNA nanoparticle with the aim of preventing the potential enzymatic degradation from the environmental nucleases. Hence, hundreds of times prolonged survival and retention was determined in pertinent to the blood circulation properties. Additionally, the installation of a guide ligand at the distal end of PEG segments was proposed to encourage selective tumor uptake. A linear peptide of GPLGVRG, which is selectively susceptible to digestion by the tumor-enriched matrix metalloproteinase 2 (MMP-2), was used as the linkage between the shell and core. This peptide has been shown to detach the bio-inert PEGylation, resulting in further facilitated cell endocytosis and intracellular trafficking activities. Hence, the precisely defined synthetic nanomedicine, which exhibits desirable characteristics, efficient expression of the therapeutic gene in the affected cells, and contributed to potent therapeutic efficacy in systemic treatment of intractable tumors by encapsulating the anti-angiogenic gene., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Because of their unique electromechanical coupling response, piezoelectric smart biomaterials demonstrated distinctive capability toward effective, efficient, and quick diagnosis and treatment of a wide range of diseases. Such materials have potentiality to be utilized as wireless therapeutic methods with ultrasonic stimulation, which can be used as self-powered biomedical devices. An emerging advancement in the realm of personalized healthcare involves the utilization of piezoelectric biosensors for a range of therapeutic diagnosis such as diverse physiological signals in the human body, viruses, pathogens, and diseases like neurodegenerative ones, cancer, etc. The combination of piezoelectric nanoparticles with ultrasound has been established as a promising approach in sonodynamic therapy and piezocatalytic therapeutics and provides appealing alternatives for noninvasive treatments for cancer, chronic wounds, neurological diseases, etc. Innovations in implantable medical devices (IMDs), such as implantable piezoelectric energy generator (iPEG), offer significant advantages in improving physiological functioning and ability to power a cardiac pacemaker and restore the heart function. This comprehensive review critically evaluates the role of piezoelectricity in disease diagnosis and treatment, highlighting the implication of piezoelectric smart biomaterials for biomedical devices. It also discusses the potential of piezoelectric materials in healthcare monitoring, tissue engineering, and other medical applications while emphasizing future trends and challenges in the field.

Poly(lactide- co -glycolide) (PLGA) is a biocompatible and biodegradable copolymer that has gained high acceptance in biomedical applications. In the present study, PLGA ( M w = 13,900) was synthesized by ring-opening polymerization in the presence of a biocompatible zinc-proline initiator through a green route. Irinotecan (Ir) loaded with efficient PLGA core-lipid shell hybrid nanocarriers (lipomers, LPs) were formulated with 1,2-distearoyl- sn -glycero-3-phosphoethanolamine and 1,2-distearoyl- sn -glycero-3-phosphoethanolamine- N -[amino (polyethylene glycol)-2000] (DSPE-PEG-2000), using soya lecithin, by a nanoprecipitation method, and the fabricated LPs were designated as P-DSPE-Ir and P-DSPE-PEG-Ir, respectively. The formulated LPs were further validated for their physicochemical properties and biological potential for colon cancer application. The potential delivery of a poorly water-soluble chemotherapeutic drug (Ir) was studied for the treatment of colon cancer. LPs were successfully prepared, providing controlled size (80-120 nm) and surface charge (∼ -35 mV), and the sustained release properties and cytotoxicity against CT-26 colon cancer cells were studied. The in vivo biodistribution and tumor site retention in CT-26 xenograft tumor-bearing Balb/C mice showed promising results for tumor uptake and retention for a prolonged time period. Unlike P-DSPE-Ir, the P-DSPE-PEG-Ir LP exhibited significant tumor growth delay as compared to untreated and blank formulation-treated groups in CT-26 (subcutaneous tumor model) after 4 treatments of 10 mg irinotecan/kg dose. The biocompatibility and safety of the LPs were confirmed by an acute toxicity study of the optimized formulation. Overall, this proof-of-concept study demonstrates that the PLGA-based LPs improve the efficacy and bioavailability and decrease neutropenia of Ir to combat colon cancer.

Clinical oncology is currently experiencing a technology bottleneck due to the expeditious evolution of therapy defiance in tumors. Although drugs used in chemotherapy work for a sort of cell death with potential clinical application, the effectiveness of chemotherapy-inducing drugs is subject to several endogenous conditions when used alone, necessitating the urgent need for controlled mechanisms. A tumor-targeted drug delivery therapy using Li-Al (M + /M 3+ )-based layered double hydroxide (LDHs) family has been proposed with the general chemical formula [M + 1- x M 3+ x (OH)] 2 x + [(A m- ) 2 x / m . n (H 2 O)] 2 x - , which is fully biodegradable and works in connection with the therapeutic interaction between LDH nanocarriers and anticancerous doxorubicin (DOX). Compositional variation of Li and Al in LDHs has been used as a nanoplatform, which provides a functional balance between circulation lifetime, drug loading capacity, encapsulation efficiency, and tumor-specific uptake to act as self-regulatory therapeutic cargo to be released intracellularly. First-principle analyses based on DFT have been employed to investigate the interaction of bonding and electronic structure of LDH with DOX and assess its capability and potential for a superior drug carrier. Following the internalization into cancer cells, nanoformulations are carried to the nucleus via lysosomes, and the mechanistic pathways have been revealed. Additionally, in vitro along with in vivo therapeutic assessments on melanoma-bearing mice show a dimensional effect of nanoformulation for better biocompatibility and excellent synergetic anticancer activity. Further, the severe toxic consequences associated with traditional chemotherapy have been eradicated by using injectable hydrogel placed just beneath the tumor site, and regulated release of the drug has been confirmed through protein expression applying various markers. However, Li-Al-based LDH nanocarriers open up new design options for multifunctional nanomedicine, which has intriguing potential for use in cancer treatment through sustained drug delivery.

Ferroptosis is an appealing cancer therapy strategy based on the H 2 O 2 -involved Fenton reaction to produce toxic • OH for lipid peroxidation. However, intracellular H 2 O 2 is easily consumed and results in a deficient Fenton reaction. This obstacle can be overcome by traditional chemotherapeutic drugs for H 2 O 2 supplements. Moreover, a recent work illustrated that dihydroartemisinin (DHA) could promote ferroptosis against tumoral cells, particularly in the presence of ferrous compounds. To achieve combined chemotherapy and ferroptosis, a nanocarrier ( TK NP DHA -Fc) was constructed by using thioketal (TK)-bridged paclitaxel prodrug (PEG-TK-PTX) and ferrocene (Fc)-conjugated PEG-Fc, where DHA was encapsulated by a hydrophobic-hydrophobic interaction. Upon cellular uptake, TK NP DHA -Fc could facilitate PTX release through TK breakage under an excess H 2 O 2 microenvironment. Owing to the loss of the hydrophobic PTX component, TK NP DHA -Fc underwent a rapid dissociation for improving DHA to act as a ferroptotic inducer along with Fe supplied from Fc. Moreover, both the chemotherapy-induced reactive oxygen species and the • OH produced from reinforced ferroptosis further stimulated the TK cleavage. The "self-catalytic" loop of TK NP DHA -Fc remarkably improved the antitumor performance in vivo via combined mechanisms, and its tumor inhibition rate reached 78.3%. This work highlights the contribution of ROS-responsive and self-catalytic nanoplatforms for enhancing the potential of combined chemotherapy and ferroptosis for cancer therapy in the future.

Photochemotherapy has been recognized as a promising combinational modality for cancer treatment. However, difficulties such as off-target drug delivery, systemic toxicity, and the hypoxic nature of the tumor microenvironment remain hindrances to its application. To overcome these challenges, cancer cell membrane camouflaged perfluorooctyl bromide (PFOB) dual-layer nanopolymersomes bearing indocyanine green (ICG) and camptothecin (CPT), named MICFNS, were developed in this study, and melanoma was exploited as the model for MICFNS manufacture and therapeutic application. Our data showed that MICFNS were able to stabilize both ICG and CPT in the nanocarriers and can be quickly internalized by B16F10 cells due to melanoma membrane-mediated homology. Upon NIR irradiation, MICFNS can trigger hyperthermia and offer enhanced singlet oxygen production due to the incorporation of PFOB. With ≥10/2.5 μM ICG/CPT, MICFNS + NIR can provide comparable in vitro cancericidal effects to those caused by using an 8-fold higher dose of encapsulated CPT alone. Through the animal study, we further demonstrated that MICFNS can be quickly brought to tumors and have a longer retention time than those of free agents in vivo . Moreover, the MICFNS with 40/10 μM ICG/CPT in combination with 30 s NIR irradiation can successfully inhibit tumor growth without systemic toxicity in mice within the 14 day treatment. We speculate that such an antitumoral effect was achieved by phototherapy followed by chemotherapy, a two-stage tumoricidal process performed by MICFNS. Taken together, we anticipate that MICFNS, a photochemotherapeutic nanoplatform, has high potential for use in clinical anticancer treatment.

Photothermal therapy (PTT) provides a great prospect for noninvasive cancer therapy. However, it is still highly challenging to construct photothermal agents (PTAs) with the desired performances for imaging-guided PTT applications. Herein, a D-A-D-type naphthalene diamine (NDI)-based photothermal nano-PTAs NDS-BPN NP with near-infrared region (NIR) emission at 822 nm, aggregation-induced emission (AIE), high photothermal conversion efficiency (55.05%), and excellent photothermal stability is successfully designed and prepared through a simple two-step engineering method by using a new AIE molecule NDS-BPN and DSPE-PEG2000 as precursors. The prepared PTT nanoagents NDS-BPN NPs have been further applied for efficient photothermal ablation of cancer cells in vitro and also achieved the NIR fluorescent image-guided PTT tumor therapy in vivo with satisfactory results. We believe that this work provides an attractive NIR AIE NDI-based nano-PTA for the phototherapy of tumors as well as develops the construction strategy of NDI molecular-based photothermal nanoagents with desired performances for imaging-guided PTT.

Acute kidney injury (AKI) is a disease that is characterized by a rapid decline in renal function and has a relatively high incidence in hospitalized patients. Sepsis, renal hypoperfusion, and nephrotoxic drug exposure are the main causes of AKI. The major therapy measures currently include supportive treatment, symptomatic treatment, and kidney transplantation. These methods are supportive treatments, and their results are not satisfactory. Fortunately, many new treatments that markedly improve the AKI therapy efficiency are emerging. These include antioxidant therapy, ferroptosis therapy, anti-inflammatory therapy, autophagy therapy, and antiapoptotic therapy. In addition, the development of nanotechnology has further promoted therapeutic effects on AKI. In this review, we highlight recent advances in the development of nanocarriers for AKI drug delivery. Emphasis has been placed on the latest developments in nanocarrier modification and design. We also summarize the applications of different nanocarriers in AKI treatment. Finally, the advantages and challenges of nanocarrier applications in AKI are summarized, and several nanomedicines that have been approved for clinical trials to treat diverse kidney diseases are listed.

Pancreatic ductal adenocarcinoma (PDAC) poses a formidable challenge due to its aggressive nature and poor prognosis. Gemcitabine (Gem), a primary therapeutic option, functions by inhibiting DNA synthesis and promoting apoptosis, thereby impeding the progression of PDAC. However, Gem is hindered by suboptimal pharmacokinetics and efficacy. In response to these challenges, we have developed a nanoparticle (NP) designed for specific recognition of plectin-1 in PDAC cell membranes. The NPs encapsulate Gem while demonstrating pH-responsive drug release characteristics in the acidic tumor microenvironment. This targeted approach enhances local drug delivery while alleviating concerns about systemic toxicity. Furthermore, the NPs are enriched with indocyanine green (ICG), renowned for its strong photothermal effects, thereby further enhancing therapeutic outcomes. This study presents an innovative therapeutic strategy for PDAC based on a plectin-1-targeted recognition delivery approach. The approach is applied to enhance chemotherapy, combined with photothermal therapy (PTT), inducing apoptosis in PDAC cell lines and improving the pharmacokinetics of Gem. In conclusion, the delivery strategy based on plectin-1-targeted recognition shows promising preclinical prospects for enhancing therapeutic efficacy in PDAC, offering valuable insights for future clinical applications.

Cancer immunotherapy represents a promising targeted treatment by leveraging the patient's immune system or adoptive transfer of active immune cells to selectively eliminate cancer cells. Despite notable clinical successes, conventional immunotherapies face significant challenges stemming from the poor infiltration of endogenous or adoptively transferred cytotoxic T cells in tumors, immunosuppressive tumor microenvironment and the immune evasion capability of cancer cells, leading to limited efficacy in many types of solid tumors. Overcoming these hurdles is essential to broaden the applicability of immunotherapies. Recent advances in nanotherapeutics have emerged as an innovative tool to overcome these challenges and enhance the therapeutic potential of tumor immunotherapy. The unique biochemical and biophysical properties of nanomaterials offer advantages in activation of immune cells in vitro for cell therapy, targeted delivery, and controlled release of immunomodulatory agents in vivo . Nanoparticles are excellent carriers for tumor associated antigens or neoantigen peptides for tumor vaccine, empowering activation of tumor specific T cell responses. By precisely delivering immunomodulatory agents to the tumor site, immunoactivating nanoparticles can promote tumor infiltration of endogenous T cells or adoptively transferred T cells into tumors, to overcoming delivery and biological barriers in the tumor microenvironment, augmenting the immune system's ability to recognize and eliminate cancer cells. This review provides an overview of the current advances in immunotherapeutic approaches utilizing nanotechnology. With a focus on discussions concerning strategies to enhance activity and efficacy of cytotoxic T cells and explore the intersection of engineering nanoparticles and immunomodulation aimed at bolstering T cell-mediated immune responses, we introduce various nanoparticle formulations designed to deliver therapeutic payloads, tumor antigens and immunomodulatory agents for T cell activation. Diverse mechanisms through which nanoparticle-based approaches influence T cell responses by improving antigen presentation, promoting immune cell trafficking, and reprogramming immunosuppressive tumor microenvironments to potentiate anti-tumor immunity are examined. Additionally, the synergistic potential of combining nanotherapeutics with existing immunotherapies, such as immune checkpoint inhibitors and adoptive T cell therapies is explored. In conclusion, this review highlights emerging research advances on activation of cytotoxic T cells using nanoparticle agents to support the promises and potential applications of nanoparticle-based immunomodulatory agents for cancer immunotherapy.

Hafnium nitride nanoparticles (HfN NPs) can offer appealing plasmonic properties at the nanoscale, but the fabrication of stable water-dispersible solutions of non-toxic HfN NPs exhibiting plasmonic features in the window of relative biological transparency presents a great challenge. Here, we demonstrate a solution to this problem by employing ultrashort (femtosecond) laser ablation from a HfN target in organic solutions, followed by a coating of the formed NPs with polyethylene glycol (PEG) and subsequent dispersion in water. We show that the fabricated NPs exhibit plasmonic absorption bands with maxima around 590 nm, 620 nm, and 650 nm, depending on the synthesis environment (ethanol, acetone, and acetonitrile, respectively), which are largely red-shifted compared to what is expected from pure HfN NPs. The observed shift is explained by including nitrogen-deficient hafnium nitride and hafnium oxynitride phases inside the core and oxynitride coating of NPs, as follows from a series of structural characterization studies. We then show that the NPs can provide a strong photothermal effect under 808 nm excitation with a photothermal conversion coefficient of about 62%, which is comparable to the best values reported for plasmonic NPs. MTT and clonogenic assays evidenced very low cytotoxicity of PEG-coated HfN NPs to cancer cells from different tissues up to 100 μg mL -1 concentrations. We finally report a strong photothermal therapeutic effect of HfN NPs, as shown by 100% cell death under 808 nm light irradiation at NP concentrations lower than 25 μg mL -1 . Combined with additional X-ray theranostic functionalities (CT scan and photon capture therapy) profiting from the high atomic number ( Z = 72) of Hf, plasmonic HfN NPs promise the development of synergetically enhanced modalities for cancer treatment.

In the process of tumor metastasis, tumor cells can acquire invasion by excessive uptake of nutrients and energy and interact with the host microenvironment to shape a premetastatic niche (PMN) that facilitates their colonization and progression in the distal sites. Pyruvate is an essential nutrient that engages in both energy metabolism and remodeling of the extracellular matrix (ECM) in the lungs for PMN formation, thus providing a target for tumor metastasis treatment. There is a paucity of strategies focusing on PMN prevention, which is key to metastasis inhibition. Here, we design a bioresponsive nanoparticle (HP/GU) based on a disulfide-cross-linked hyperbranched polyethylenimine (D-PEI) core and a hyaluronic acid (HA) shell with a reactive oxygen species (ROS)-sensitive cross-linker between them to encapsulate glucose oxidase (GOX) and a mitochondrial pyruvate carrier (MPC) inhibitor via electrostatic interaction, which reinforces starvation therapy and reduces PMN formation in the lungs via inhibiting pyruvate metabolism. In tumor cells, GOX and MPC inhibitors can be rapidly released and synergistically reduce the energy supply of tumor cells by consuming glucose and inhibiting pyruvate uptake to decrease tumor cell invasion. MPC inhibitors can also reduce ECM remodeling by blocking cellular pyruvate metabolism to prevent PMN formation. Consequently, HP/GU achieves an efficient inhibition of both primary and metastatic tumors and provides an innovative strategy for the treatment of tumor metastases.

The therapeutic effectiveness of photothermal therapy (PTT) is limited by heat tolerance and PTT-induced inflammation, which increases the risk of tumor metastasis and recurrence. Ferroptosis combined with PTT can achieve significant therapeutic effects. In this work, we designed self-healing photothermal nanotherapeutics to achieve effective PTT with triple-amplified ferroptosis and cascade inflammation inhibition after photothermal treatment. After the ferroptosis-inducing ability of mangiferin (MF) was first elucidated, the nanocomplex PFeM, coordinated by Fe 3+ and MF with polyvinylpyrrolidone (PVP) modification, was prepared by a one-pot self-assembly method. PFeM with laser irradiation could induce intensified ferroptosis by integrating the functions of MF to deactivate glutathione peroxidase 4, Fe 3+ /Fe 2+ to generate lethal reactive oxygen species via the Fenton reaction, and the photothermal effect to amplify ferroptosis. More importantly, the released MF could achieve cascade inflammation inhibition, thereby reversing the proinflammatory microenvironment caused by PTT. The in vivo antitumor and anti-inflammatory effects of PFeM were further confirmed in a 4T1 tumor-bearing mouse model. This study expounding the ferroptosis-inducing effects of MF and utilizing the strategy of chelating MF with iron ions can provide a new idea for developing photothermal nanoagents with clinically convertible safety ingredients and a green preparation process that improve efficacy and reduce adverse reactions during PTT.

Immunotherapy has revolutionized the cancer treatment paradigm, yet efficient immunotherapeutic responses against immune-cold/desert cancers remain challenging. Herein, we report that photoactivatable nanoagonists yield a potent antitumor synergy of photoimmunotherapy against pancreatic ductal adenocarcinoma (PDAC). The nanoagonist was fabricated by assembling an amphiphilic boron dipyrromethene-derived polymer conjugated with a Toll-like receptor agonist via a photocleavable linker and stimulator of interferon genes agonist. The nanoagonist enables light-induced generation of reactive oxygen species and on-demand release of the agonists to yield synergistic photoimmunotherapy. The produced tumor antigens promote dendritic cell maturation, which is further amplified by these agonists for eliciting adaptive immunity, accompanied by apparently abscopal and long-term memory effects. The nanoagonist further alleviates the fibrosis of tumor stroma and the immunosuppressive microenvironment, leading to the deep infiltrations of clinically used therapeutics and immune cells to yield preferable combinational treatments against PDAC models. These results provide valuable insights into activatable nanoparticles for cancer therapy against immune-desert cancers.

Chemotherapy as a common anticancer therapeutic modality is often challenged by various obstacles such as poor stability, low solubility, and severe side effects of chemotherapeutic agents as well as multidrug resistance of cancerous cells. Nanoparticles in the role of carriers for chemotherapeutic drugs and platforms for combining different therapeutic approaches have effectively participated in overcoming such drawbacks. In particular, nanoparticles able to induce their therapeutic effect in response to specific stimuli like tumor microenvironment characteristics (e.g., hypoxia, acidic pH, high levels of glutathione, and overexpressed hydrogen peroxide) or extrinsic stimulus of laser light bring about more precise and selective treatments. Among them, nanostructures of covalent organic frameworks (COFs) have drawn great interest in biomedical fields during recent years. Possessing large surface area, high porosity, structural stability, and customizable architecture, these biocompatible porous crystalline polymers properly translate to promising platforms for drug delivery and induction of combination therapies. With the focus on stimuli-responsive characteristics of nanoscale COFs, this study aims to propose an overview of their potentiality in cancer treatment on the basis of chemotherapy alone or in combination with sonodynamic, chemodynamic, photodynamic, and photothermal therapies.

Brachytherapy stands as an essential clinical approach for combating locally advanced tumors. Here, an injectable brachytherapy hydrogel is developed for the treatment of both local and metastatic tumor. Fe-tannins nanoparticles are efficiently and stably radiolabeled with clinical used therapeutic radionuclides (such as 131 I, 90 Y, 177 Lu, and 225 Ac) without a chelator, and then chemically cross-linked with 4-armPEG-SH to form brachytherapy hydrogel. Upon intratumoral administration, magnetic resonance imaging (MRI) signal from ferric ions embedded within the hydrogel directly correlates with the retention dosage of radionuclides, which can real-time monitor radionuclides emitting short-range rays in vivo without penetration limitation during brachytherapy. The hydrogel's design ensures the long-term tumor retention of therapeutic radionuclides, leading to the effective eradication of local tumor. Furthermore, the radiolabeled hydrogel is integrated with an adjuvant to synergize with immune checkpoint blocking therapy, thereby activating potent anti-tumor immune responses and inhibiting metastatic tumor growth. Therefore, this work presents an imageable brachytherapy hydrogel for real-time monitoring therapeutic process, and expands the indications of brachytherapy from treatment of localized tumors to metastatic tumors., (© 2024 Wiley‐VCH GmbH.)

Photodynamic therapy (PDT), as one of the most promising cancer therapy methods, is still limited by several drawbacks, such as tissue hypoxia and shallow light penetration of blue-violet light (200-450 nm), and red light (750 nm) is more penetrating to tissues than blue-violet light, but still lower than near-red light (750-1350 nm). Therefore, we proposed a synergistic therapy system by combining the near-infrared light-triggered PDT with nitric oxide (NO)-based gas therapy to enhance the anti-tumor effects. Upconversion nanoparticles (UCNPs) were loaded with the photosensitizers of ZnPc and the NO donors of l-arginine (L-Arg) to obtain the nanocomposites of UCN@mSiO 2 @ZnPc@L-Arg. Under 980 nm laser irradiation, reactive oxygen species (ROS) could be produced for PDT and react with l-Arg to produce NO, which is previously reported to have a greater killing effect on tumor cells than ROS and also plays an important role in promoting PDT in our study. Both the in vitro and in vivo tests demonstrated that the combined therapy of PDT with NO therapy could enhance the tumor killing effect significantly compared with the unique application of PDT. The UCNPs-based nanocomposites are expected to be widely used in biomedicine for tumor inhibition., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Solid tumors create a hypoxic microenvironment and this character can be utilized for cancer therapy, but the hypoxia levels are insufficient to achieve satisfactory therapeutic benefits. Some tactics have been used to improve hypoxia, which however will cause side effects due to the uncontrolled drug release. We herein report near-infrared (NIR) photoactivatable three-in-one nanoagents (PCT) to aggravate tumor hypoxia and enable amplified photo-combinational chemotherapy. PCT are formed based on a thermal-responsive liposome nanoparticle containing three therapeutic agents: a hypoxia responsive prodrug tirapazamine (TPZ) for chemotherapy, a vascular targeting agent combretastatin A-4 (CA4) for vascular disturbance and a semiconducting polymer for both photodynamic therapy (PDT) and photothermal therapy (PTT). With NIR laser irradiation, PCT generate heat for PTT and destructing thermal-responsive liposomes to achieve activatable releases of TPZ and CA4. Moreover, PCT produce singlet oxygen ( 1 O 2 ) for PDT via consuming tumor oxygen. CA4 can disturb the blood vessels in tumor microenvironment to aggravate the hypoxic microenvironment, which results in the activation of TPZ for amplified chemotherapy. PCT thus enable PTT, PDT and hypoxia-amplified chemotherapy to afford a high therapeutic efficacy to almost absolutely eradicate subcutaneous 4 T1 tumors and effectively inhibit tumor metastases in lung and liver. This work presents an activatable three-in-one therapeutic nanoplatform with remotely controllable and efficient therapeutic actions to treat cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Breast cancer appears as the major cause of cancer-related deaths in women, with more than 2 260 000 cases reported worldwide in 2020, resulting in 684 996 deaths. Triple-negative breast cancer (TNBC), characterized by the absence of estrogen, progesterone, and human epidermal growth factor type 2 receptors, represents ≈20% of all breast cancers. TNBC has a highly aggressive clinical course and is more prevalent in younger women. The standard therapy for advanced TNBC is chemotherapy, but responses are often short-lived, with high rate of relapse. The lack of therapeutic targets and the limited therapeutic options confer to individuals suffering from TNBC the poorest prognosis among breast cancer patients, remaining a major clinical challenge. In recent years, advances in cancer nanomedicine provided innovative therapeutic options, as nanoformulations play an important role in overcoming the shortcomings left by conventional therapies: payload degradation and its low solubility, stability, and circulating half-life, and difficulties regarding biodistribution due to physiological and biological barriers. In this integrative review, the recent advances in the nanomedicine field for TNBC treatment, including the novel nanoparticle-, exosome-, and hybrid-based therapeutic formulations are summarized and their drawbacks and challenges are discussed for future clinical applications., (© 2023 The Authors. Small published by Wiley‐VCH GmbH.)

The recent decade has witnessed a remarkable surge in the field of nanoparticles, from their synthesis, characterization, and functionalization to diverse applications. At the nanoscale, these particles exhibit distinct physicochemical properties compared to their bulk counterparts, enabling a multitude of applications spanning energy, catalysis, environmental remediation, biomedicine, and beyond. This review focuses on specific nanoparticle categories, including magnetic, gold, silver, and quantum dots (QDs), as well as hybrid variants, specifically tailored for biomedical applications. A comprehensive review and comparison of prevalent chemical, physical, and biological synthesis methods are presented. To enhance biocompatibility and colloidal stability, and facilitate surface modification and cargo/agent loading, nanoparticle surfaces are coated with different synthetic polymers and very recently, cell membrane coatings. The utilization of polymer- or cell membrane-coated nanoparticles opens a wide variety of biomedical applications such as magnetic resonance imaging (MRI), hyperthermia, photothermia, sample enrichment, bioassays, drug delivery, etc. With this review, the goal is to provide a comprehensive toolbox of insights into polymer or cell membrane-coated nanoparticles and their biomedical applications, while also addressing the challenges involved in translating such nanoparticles from laboratory benchtops to in vitro and in vivo applications. Furthermore, perspectives on future trends and developments in this rapidly evolving domain are provided., (© 2024 Wiley‐VCH GmbH.)

Endometrial cancer is the most common gynecological malignancy worldwide and unfortunately has a much higher mortality rate in Black women compared with White women. Many potential factors contribute to these mortality rates, including the underlying effects of systemic and interpersonal racism. Furthermore, other trends in medicine have potential links to these rates including participation in clinical trials, hormone therapy, and pre-existing health conditions. Addressing the high incidence and disparate mortality rates in endometrial cancer requires novel methods, such as nanoparticle-based therapeutics. These therapeutics have been growing in increasing prevalence in pre-clinical development and have far-reaching implications in cancer therapy. The rigor of pre-clinical studies is enhanced by the likeness of the model to the human body. In systems for 3D cell culture, for example, the extracellular matrix mimics the tumor more closely. The increasing emphasis on precision medicine can be applied to cancer using nanoparticle-based methods and applied to pre-clinical models by using patient-derived model data. This review highlights the intersections of nanomedicine, precision medicine, and racial disparities within endometrial cancer and provides insights into reducing health disparities using recent scientific advances on the nanoscale., (© 2023 Wiley‐VCH GmbH.)

Bladder cancer (BC) is one of the most common malignant neoplasms of the genitourinary system. Traditional BC therapies include chemotherapy, targeted therapy, and immunotherapy. However, limitations such as lack of specificity, cytotoxicity, and multidrug resistance pose serious challenges to the benefits of BC therapies. Consequently, current studies focus on the search for new therapeutic solutions. In recent years, there has been a growing interest in using nanotechnology in the treatment of both non-invasive (NMIBC) and invasive bladder cancer (MIBC). Nanotechnology is based on the use of both organic molecules (chitosan, liposomes) and inorganic molecules (superparamagnetic iron oxide nanoparticles) as carriers of active substances. The main aim of such molecules is the targeted transport and prolonged retention of the drug in the target tissue, which increases the therapeutic efficacy of the active substance. This review discusses the numerous types of nanoparticles (including chitosan, polymeric nanoparticles, liposomes, and protein nanoparticles), targeting mechanisms, and approved nanotherapeutics with oncological implications in cancer treatment. We also present nanoformulation applications in phototherapy, gene therapy, and immunotherapy. Moreover, we summarise the current perspectives, advantages, and challenges in clinical translation.

The critical and unmet medical need for novel therapeutic advancements in the treatment of age-related macular degeneration (AMD) cannot be overstated, particularly given the aging global population and the increasing prevalence of this condition. Current AMD therapy involves intravitreal treatments that require monthly or bimonthly injections to maintain optimal efficacy. This underscores the necessity for improved approaches, prompting recent research into developing advanced drug delivery systems to prolong the intervals between treatments. Nanoparticle-based therapeutic approaches have enabled the controlled release of drugs, targeted delivery of therapeutic materials, and development of smart solutions for the harsh microenvironment of diseased tissues, offering a new perspective on ocular disease treatment. This review emphasizes the latest pre-clinical treatment options in ocular drug delivery to the retina and explores the advantages of nanoparticle-based therapeutic approaches, with a focus on AMD, the leading cause of irreversible blindness in the elderly.

Adjusting the catalytic activity of nanozymes for enhanced oncotherapy has attracted significant interest. However, it remains challenging to engineer regulatory tactics with a minimal impact on normal tissues. By exploiting the advantages of energy storage, photostimulated, and long afterglow luminescence of persistent nanoparticles (PLNPs), a persistent luminescence-based nanoreservoir was produced to improve its catalytic activity for benign oncotherapy. In the study, PLNPs in a nanoreservoir with the ability to store photons served as a self-illuminant to promote its peroxidase-like activity and therapeutic efficacy by persistently motivating its photothermal effect before and after external irradiation ceased. The photostimulated and persistent luminescence of PLNPs and spatiotemporal controllability of exogenous light jointly alleviated adverse effects induced by prolonged irradiation and elevated the catalytic capability of the nanoreservoir. Ultimately, the system fulfilled benign photothermal-intensive nanozymatic therapy. This work provides new insights into boosting the catalytic activity of nanozymes for secure disease treatment.

Systemic infection with Candida albicans poses a significant risk for people with weakened immune systems and carries a mortality rate of up to 60%. However, current therapeutic options have several limitations, including increasing drug tolerance, notable off-target effects, and severe adverse reactions. Over the past four decades, the progress in developing drugs to treat Candida albicans infections has been sluggish. This comprehensive review addresses the limitations of existing drugs and summarizes the efforts made toward redesigning and innovating existing or novel drugs through nanotechnology. The discussion explores the potential applications of nanomedicine in Candida albicans infections from four perspectives: nano-preparations for anti-biofilm therapy, innovative formulations of "old drugs" targeting the cell membrane and cell wall, reverse drug resistance therapy targeting subcellular organelles, and virulence deprivation therapy leveraging the unique polymorphism of Candida albicans. These therapeutic approaches are promising to address the above challenges and enhance the efficiency of drug development for Candida albicans infections. By harnessing nano-preparation technology to transform existing and preclinical drugs, novel therapeutic targets will be uncovered, providing effective solutions and broader horizons to improve patient survival rates., (© 2024. The Author(s).)

How to develop contrast agents for cancer theranostics is a meaningful and challenging endeavor, and rare earth nanoparticles (RENPs) may provide a possible solution. In this study, we initially modified RENPs through the application of photodynamic agents (ZnPc) and targeted the bevacizumab antibody for cancer theranostics, which was aimed at improving the therapeutic targeting and efficacy. Subsequently, we amalgamated anthocyanin with the modified RENPs, creating a potential cancer diagnosis platform. When the spectral data were obtained from the composite of cells, the crucial information was extracted through a competitive adaptive reweighted sampling feature algorithm. Then, we employed a machine learning classification model and classified both the individual spectral data and fused spectral data to accurately predict distinctions between breast cancer and normal tissue. The results indicate that the amalgamation of fusion techniques with machine learning algorithms provides highly precise predictions for molecular-level breast cancer detection. Finally, in vitro and in vivo experiments were carried out to validate the near-infrared luminescence and therapeutic effectiveness of the modified nanomedicine. This research not only underscores the targeted effects of nanomedicine but also demonstrates the potent synergy between optical spectral technology and machine learning. This innovative approach offers a comprehensive strategy for the integrated treatment of breast cancer.

There are currently no targeted delivery systems to satisfactorily treat bone-related disorders. Many clinical drugs consisting of small organic molecules have a short circulation half-life and do not effectively reach the diseased tissue site. This coupled with repeatedly high dose usage that leads to severe side effects. With the advance in nanotechnology, drugs contained within a nano-delivery device or drugs aggregated into nanoparticles (nano-drugs) have shown promises in targeted drug delivery. The ability to design nanoparticles to target bone has attracted many researchers to develop new systems for treating bone related diseases and even repurposing current drug therapies. In this review, we shall summarise the latest progress in this area and present a perspective for future development in the field. We will focus on calcium-based nanoparticle systems that modulate calcium metabolism and consequently, the bone microenvironment to inhibit disease progression (including cancer). We shall also review the bone affinity drug family, bisphosphonates, as both a nano-drug and nano-delivery system for bone targeted therapy. The ability to target and release the drug in a controlled manner at the disease site represents a promising safe therapy to treat bone diseases in the future., (© 2024. The Author(s).)

In 2020, the top 10 causes of death among children and adolescents between the ages of 1 and 19 years old included cancer, congenital anomalies, heart disease, and chronic respiratory disease; all these conditions are potentially treatable with medical intervention. However, children exhibit specific physiological and developmental characteristics that can significantly impact drug pharmacokinetics, pharmacodynamics, and safety profile. These factors illustrate the importance of a heightened focus on pediatric drug development. Traditional drugs lack proper circulation, permeability, targeting, accumulation, and release, and they often require dose adjustments or modifications, which can result in suboptimal therapeutic outcomes and increased risks of adverse effects in pediatric patients. Nanomedicines have emerged as efficient drug delivery systems because of their unique properties, which can improve the solubility and stability of drugs by encapsulating them in different forms of nanoparticles. This review discusses the challenges of pediatric therapy, and the current state of nanomedicines for pediatric diseases in terms of Food and Drug Administration-approved nanomedicines, the types of diseases treated or diagnosed, and preclinical studies that have the potential to be translated to the clinic. In summary, nanomedicine holds significant potential for addressing the unique and pressing challenges associated with diagnosing and treating pediatric diseases., (© 2024 The Author(s). WIREs Nanomedicine and Nanobiotechnology published by Wiley Periodicals LLC.)

Numerous studies are focused on nanoparticle penetration into the brain functionalizing them with ligands useful to cross the blood-brain barrier. However, cell targeting is also crucial, given that cerebral pathologies frequently affect specific brain cells or areas. Functionalize nanoparticles with the most appropriate targeting elements, tailor their physical parameters, and consider the brain's complex anatomy are essential aspects for precise therapy and diagnosis. In this review, we addressed the state of the art on targeted nanoparticles for drug delivery in diseased brain regions, outlining progress, limitations, and ongoing challenges. We also provide a summary and overview of general design principles that can be applied to nanotherapies, considering the areas and cell types affected by the most common brain disorders. We then emphasize lingering uncertainties that hinder the translational possibilities of nanotherapies for clinical use. Finally, we offer suggestions for continuing preclinical investigations to enhance the overall effectiveness of precision nanomedicine in addressing neurological conditions. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies., (© 2024 The Author(s). WIREs Nanomedicine and Nanobiotechnology published by Wiley Periodicals LLC.)

Phototherapy has garnered significant attention in the past decade. Photothermal and photodynamic synergistic therapy combined with NIR fluorescence imaging has been one of the most attractive treatment options because of the deep tissue penetration, high selectivity and excellent therapeutic effect. Benefiting from the superb photometrics and ease of modification, perylene diimide (PDI) and its derivatives have been employed as sensing probes and therapeutic agents in the biological and biomedical research fields, and exhibiting excellent potential. Herein, we reported the development of a novel organic small-molecule phototherapeutic agent, PDI-TN. The absorption of PDI-TN extends into the NIR region, which provides feasibility for NIR phototherapy. PDI-TN overcomes the traditional Aggregation-Caused Quenching (ACQ) effect and exhibits typical characteristics of Aggregation-Induced Emission (AIE). Subsequently, PDI-TN NPs were obtained by using an amphiphilic triblock copolymer F127 to encapsulate PDI-TN. Interestingly, the PDI-TN NPs not only exhibit satisfactory photothermal effects, but also can generate O 2 •- and 1 O 2 through type I and type II pathways, respectively. Additionally, the PDI-TN NPs emit strong fluorescence in the NIR-II region, and show outstanding therapeutic potential for in vivo NIR-II fluorescence imaging. To our knowledge, PDI-TN is the first PDI derivative used for NIR-II fluorescence imaging-guided photodynamic and photothermal synergistic therapy, which suggests excellent potential for future biological/biomedical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Acute myocardial infarction (AMI) resulting from coronary artery occlusion stands as the predominant cause of cardiovascular disability and mortality worldwide. An all-encompassing treatment strategy targeting pathological processes of oxidative stress, inflammation, proliferation and fibrotic remodeling post-AMI is anticipated to enhance therapeutic outcomes. Herein, an up-down-structured bilayer microneedle (Ce-CLMs-BMN) with reactive oxygen species (ROS) and ultrasound (US) dual-responsiveness is proposed for AMI in-situ sequential therapy. The upper-layer microneedle is formulated by crosslinking ROS-sensitive linker with polyvinyl alcohol loaded with cerium dioxide nanoparticles (CeNPs) featuring versatile enzyme-mimetic activities. During AMI acute phase, prompted by ischemia-induced microenvironmental redox imbalance, this layer swiftly releases CeNPs, which aid in eliminating excessive ROS and catalyzing oxygen gas (O 2 ) production through multiple enzymatic pathways, thereby alleviating oxidative stress-induced damage and modulating inflammation. In AMI chronic repair phase, micro-nano reactors (CLMs) situated in the lower-layer microneedle undergo cascade reactions with the assistance of US irradiation to generate nitric oxide (NO). As a bioactive molecule with pro-angiogenic and anti-fibrotic effects, NO expedites cardiac repair while attenuating adverse remodeling. Additionally, its antiplatelet-aggregating properties contribute to thromboprophylaxis. In-vitro and in-vivo results substantiate the efficacy of this integrated healing approach in AMI management, showcasing promising prospects for advancing infarcted heart repair., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

To fulfil the demands of rapid proliferation, tumour cells undergo significant metabolic alterations. Suppression of hyperactivated metabolism has been proven to counteract tumour growth. However, whether the reactivation of downregulated metabolic pathways has therapeutic effects remains unexplored. Here we report a nutrient-based metabolic reactivation strategy for effective melanoma treatment. L-Tyrosine-oleylamine nanomicelles (MTyr-OANPs) were constructed for targeted supplementation of tyrosine to reactivate melanogenesis in melanoma cells. We found that reactivation of melanogenesis using MTyr-OANPs significantly impeded the proliferation of melanoma cells, primarily through the inhibition of glycolysis. Furthermore, leveraging melanin as a natural photothermal reagent for photothermal therapy, we demonstrated the complete eradication of tumours in B16F10 melanoma-bearing mice through treatment with MTyr-OANPs and photothermal therapy. Our strategy for metabolism activation-based tumour treatment suggests specific nutrients as potent activators of metabolic pathways., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Chemodynamic therapy (CDT) has emerged as a transformative paradigm in the realm of reactive oxygen species -mediated cancer therapies, exhibiting its potential as a sophisticated strategy for precise and effective tumor treatment. CDT primarily relies on metal ions and hydrogen peroxide to initiate Fenton or Fenton-like reactions, generating cytotoxic hydroxyl radicals. Its notable advantages in cancer treatment are demonstrated, including tumor specificity, autonomy from external triggers, and a favorable side-effect profile. Recent advancements in nanomedicine are devoted to enhancing CDT, promising a comprehensive optimization of CDT efficacy. This review systematically elucidates cutting-edge achievements in chemodynamic nanotherapeutics, exploring strategies for enhanced Fenton or Fenton-like reactions, improved tumor microenvironment modulation, and precise regulation in energy metabolism. Moreover, a detailed analysis of diverse CDT-mediated combination therapies is provided. Finally, the review concludes with a comprehensive discussion of the prospects and intrinsic challenges to the application of chemodynamic nanotherapeutics in the domain of cancer treatment., (© 2024 Wiley‐VCH GmbH.)

Mitochondrial transplantation is an important therapeutic strategy for restoring energy supply in patients with ischaemic heart disease (IHD); however, it is limited by the invasiveness of the transplantation method and loss of mitochondrial activity. Here we report successful mitochondrial transplantation by oral administration for IHD therapy. A nitric-oxide-releasing nanomotor is modified on the mitochondria surface to obtain nanomotorized mitochondria with chemotactic targeting ability towards damaged heart tissue due to nanomotor action. The nanomotorized mitochondria are packaged in enteric capsules to protect them from gastric acid erosion. After oral delivery the mitochondria are released in the intestine, where they are quickly absorbed by intestinal cells and secreted into the bloodstream, allowing delivery to the damaged heart tissue. The regulation of disease microenvironment by the nanomotorized mitochondria can not only achieve rapid uptake and high retention of mitochondria by damaged cardiomyocytes but also maintains high activity of the transplanted mitochondria. Furthermore, results from animal models of IHD indicate that the accumulated nanomotorized mitochondria in the damaged heart tissue can regulate cardiac metabolism at the transcriptional level, thus preventing IHD progression. This strategy has the potential to change the therapeutic strategy used to treat IHD., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

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.

Opportunistic pathogenic microbial infections pose a significant danger to human health, which forces people to use riskier, more expensive, and less effective drugs compared to traditional treatments. These may be attributed to several factors, such as overusing antibiotics in medicine and lack of sanitization in hospital settings. In this context, researchers are looking for new options to combat this worrying condition and find a solution. Nanoparticles are currently being utilized in the pharmaceutical sector; however, there is a persistent worry regarding their potential danger to human health due to the usage of toxic chemicals, which makes the utilization of nanoparticles highly hazardous to eukaryotic cells. Multiple nanoparticle-based techniques are now being developed, offering essential understanding regarding the synthesis of components that play a crucial role in producing anti-microbial nanotherapeutic pharmaceuticals. In this regard, green nanoparticles are considered less hazardous than other forms, providing potential options for avoiding the extensive harm to the human microbiome that is prevalent with existing procedures. This review article aims to comprehensively assess the current state of knowledge on green nanoparticles related to antibiotic activity as well as their potential to assist antibiotics in treating opportunistic clinical phytopathogenic illnesses.

Lymphoid malignancies are complex diseases with distinct biological behaviors, clinical presentations, and treatment responses. Ongoing research and advancements in biotechnology enhance the understanding and management of these malignancies, moving towards more personalized approaches for diagnosis and treatment. Nanotechnology has emerged as a promising tool to improve some limitations of conventional diagnostics as well as treatment strategies for lymphoid malignancies. Nanoparticles (NPs) offer unique advantages such as enhanced multimodal detection, drug delivery, and targeted therapy capabilities, with the potential to improve precision medicine and patient outcomes. Here, we comprehensively examine the current landscape of nanoconstructs applied in the management of lymphoid disease. Through a comprehensive analysis of preclinical studies, we highlight the translational potential of NPs in revolutionizing the field of hematological malignancies, with a specific focus on lymphoid neoplasms.

In recent decades, immunotherapy has been considered a promising treatment approach. The modulatable enhancement or attenuation of the body's immune response can effectively suppress tumors. However, challenges persist in clinical applications due to the lack of precision in antigen presentation to immune cells, immune escape mechanisms, and immunotherapy-mediated side effects. As a potential delivery system for drugs and immunomodulators, mesoporous silica has attracted extensive attention recently. Mesoporous silica nanoparticles (MSNs) possess high porosity, a large specific surface area, excellent biocompatibility, and facile surface modifiability, making them suitable as multifunctional carriers in immunotherapy. This article summarizes the latest advancements in the application of MSNs as carriers in cancer immunotherapy, aiming to stimulate further exploration of the immunomodulatory mechanisms and the development of immunotherapeutics based on MSNs.

Introduction: Exposure to high doses of ionizing radiation can result in hematopoietic acute radiation syndrome. Currently, there is no radiation medical countermeasure approved by the U.S. FDA which can be used before radiation exposure to protect exposed individuals. Here we aimed to evaluate the therapeutic potential of an aqueous suspension of synthetic genistein nanoparticles (BIO 300) as a radioprotectant in a pilot efficacy study using a nonhuman primate model of total body irradiation., Materials and Methods: Eight rhesus macaques were divided into two groups; four received vehicle and four received BIO 300 Injectable Suspension 24 h before 5.8 Gy total-body irradiation. Survival, blood cell counts, blood chemistry, and clinical parameters were monitored over the 60 days of the study. Tissues were collected at necropsy 60 days post-irradiation or from animals that met unscheduled euthanasia criteria and subjected to histopathological analysis. Tissues analyzed included the duodenum, jejunum, ileum, sternum, lung, heart, liver, kidney, spleen, gut-associated lymphoid tissue, and urinary bladder., Results: In this pilot study, all BIO 300 Injectable Suspension treated animals survived to day 60, while only 50% of the vehicle-treated animals survived. We found that BIO 300 Injectable Suspension did not mediate an improvement in blood cell counts (e.g., neutrophils, platelets, white blood cells). However, BIO 300 Injectable Suspension treated animals had a lower incidence of fever and febrile neutropenia, were able to better maintain their body weight post radiation exposure, and exhibited less anemia and faster recovery from anemia. Histopathological analysis revealed that BIO 300-treated animals had less irradiation-induced damage to the sternum and other tissues compared to vehicle controls., Conclusions: BIO 300's mechanism of action is complex and protection against irradiation is attainable without much improvement in the complete blood count (CBC) profile. BIO 300's mechanism for radioprotection involves multiple biological pathways and systems., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2024. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Rheumatoid arthritis (RA) is a progressive autoimmune disease that mainly affects the inner lining of the synovial joints and leads to chronic inflammation. While RA is not known as lethal, recent research indicates that it may be a silent killer because of its strong association with an increased risk of chronic lung and heart diseases. Patients develop these systemic consequences due to the regular uptake of heavy drugs such as disease-modifying antirheumatic medications (DMARDs), glucocorticoids (GCs), nonsteroidal anti-inflammatory medicines (NSAIDs), etc . Nevertheless, a number of these medications have off-target effects, which might cause adverse toxicity, and have started to become resistant in patients as well. Therefore, alternative and promising therapeutic techniques must be explored and adopted, such as post-translational modification inhibitors (like protein arginine deiminase inhibitors), RNA interference by siRNA, epigenetic drugs, peptide therapy, etc ., specifically in macrophages, neutrophils, Treg cells and dendritic cells (DCs). As the target cells are specific, ensuring targeted delivery is also equally important, which can be achieved with the advent of nanotechnology. Furthermore, these nanocarriers have fewer off-site side effects, enable drug combinations, and allow for lower drug dosages. Among the nanoparticles that can be used for targeting, there are both inorganic and organic nanomaterials such as solid-lipid nanoparticles, liposomes, hydrogels, dendrimers, and biomimetics that have been discussed. This review highlights contemporary therapy options targeting macrophages, neutrophils, Treg cells, and DCs and explores the application of diverse nanotechnological techniques to enhance precision RA therapies.

Photothermal therapy (PTT) for cancers guided by optical imaging has recently shown great potential for precise diagnosis and efficient therapy. The second near-infrared window (NIR-II, 1000-1700 nm) fluorescence imaging (FLI) is highly desirable owing to its good spatial and temporal resolution, deep tissue penetration, and negligible tissue toxicity. Organic small molecules are attractive as imaging and treatment agents in biomedical research because of their low toxicity, fast clearance rate, diverse structures, ease of modification, and excellent biocompatibility. Various organic small molecules have been investigated for biomedical applications. However, there are few reports on the use of croconaine dyes (CRs), especially NIR-II emission CRs. To our knowledge, there have been no prior reports of NIR-II emissive small organic photothermal agents (SOPTAs) based on CRs. Herein, we report a croconaine dye (CR-TPE-T)-based nanoparticle (CR NP) with absorption and fluorescence emission in the NIR-I and NIR-II windows, respectively. The CR NPs exhibited intense NIR absorption, outstanding photothermal properties, and good biological compatibility. In vivo studies showed that CR NPs not only achieved real-time, noninvasive NIR-II FLI of tumors, but also induced significant tumor ablation with laser irradiation guided by imaging, without apparent side effects, and promoted the formation of antitumor immune memory in a colorectal cancer model. In addition, the CR NPs displayed efficient inhibition of breast tumor growth, improved longevity of mice and triggered efficient systemic immune responses, which further inhibited tumor metastasis to the lungs. Our study demonstrates the great potential of CRs as therapeutic agents in the NIR-II region for cancer diagnosis., (© 2024. The Author(s).)

This minireview provides an overview of the recent advancements in the development of biomimetic Aggregation-Induced Emission (AIE) nanoparticles and their applications in disease diagnosis, phototherapy, and photoimmunotherapy. AIE nanoparticles can be engineered to enable efficient image-guided photodynamic and photothermal therapies, however, challenges related to immune defense and target specificity persist. To overcome these, coating biomimetic materials on the surface of AIE nanoparticles, which mimic the features and functions of native cells, have emerged as a promising solution. This minireview will highlight the synthesis strategies and discuss the biomedical application of biomimetic AIE nanoparticles.

Neuropathic pain is a prevalent form of intermittent chronic pain, affecting approximately 7-10% of the global population. However, the current clinical administration methods, such as injection and oral administration, are mostly one-time administration, which cannot achieve accurate control of pain degree and drug dose. Herein, we developed near-infrared (NIR) light-responsive microneedle patches (MNPs) to spatiotemporally control the drug dose released to treat neuropathic pain according to the onset state. The mechanism of action utilizes upconversion nanoparticles to convert NIR light into visible and ultraviolet light. This conversion triggers the rapid rotation of the azobenzene molecular motor in the mesoporous material, enabling the on-demand controlled release of a drug dose. Additionally, MNs are used to overcome the barrier of the stratum corneum in a minimally invasive and painless manner, effectively promoting the transdermal penetration of drug molecules. The effectiveness of these patches has been demonstrated through significant results. Upon exposure to NIR light for five consecutive cycles, with each cycle lasting 30 s, the patches achieved a precise release of 318 μg of medication. In a mouse model, maximum pain relief was observed within 1 h of one cycle of NIR light exposure, with the effects lasting up to 6 h. The same level of precise treatment efficacy was maintained for subsequent pain episodes with similar light exposure. The NIR-controlled drugs precision-released MNPs provide a novel paradigm for the treatment of intermittent neuropathic pain.

Cancer remains a significant risk to human health. Nanomedicine is a new multidisciplinary field that is garnering a lot of interest and investigation. Nanomedicine shows great potential for cancer diagnosis and treatment. Specifically engineered nanoparticles can be employed as contrast agents in cancer diagnostics to enable high sensitivity and high-resolution tumor detection by imaging examinations. Novel approaches for tumor labeling and detection are also made possible by the use of nanoprobes and nanobiosensors. The achievement of targeted medication delivery in cancer therapy can be accomplished through the rational design and manufacture of nanodrug carriers. Nanoparticles have the capability to effectively transport medications or gene fragments to tumor tissues via passive or active targeting processes, thus enhancing treatment outcomes while minimizing harm to healthy tissues. Simultaneously, nanoparticles can be employed in the context of radiation sensitization and photothermal therapy to enhance the therapeutic efficacy of malignant tumors. This review presents a literature overview and summary of how nanotechnology is used in the diagnosis and treatment of malignant tumors. According to oncological diseases originating from different systems of the body and combining the pathophysiological features of cancers at different sites, we review the most recent developments in nanotechnology applications. Finally, we briefly discuss the prospects and challenges of nanotechnology in cancer., (© 2024. The Author(s).)

Acute kidney injury (AKI) is a critical medical condition characterized by high morbidity and mortality rates. The pathogenesis of AKI potentially involves bursts of reactive oxygen species (ROS) bursts and elevated levels of inflammatory mediators. Developing nanoparticles (NPs) that downregulate ROS and inflammatory mediators is a promising approach to treat AKI. However, such NPs would be affected by the glomerular filtration barrier (GFB). Typically, NPs are too large to penetrate the glomerular system and reach the renal tubules─the primary site of AKI injury. Herein, we report the development of ultrasmall carbon dots-gallic acid (CDs-GA) NPs (∼5 nm). These NPs exhibited outstanding biocompatibility and were shown not only to efficiently eliminate ROS and alleviate oxidative stress but also to suppress the activation of the NF-κB signaling pathway, leading to a reduction in the release of inflammatory factors. Importantly, CDs-GA NPs were shown to be able to rapidly accumulate rapidly in the renal tissues without the need for intricate targeting strategies. In vivo studies demonstrated that CDs-GA NPs significantly reduced the incidence of cisplatin (CDDP)-induced AKI in mice, surpassing the efficacy of the small molecular drug, N -acetylcysteine. This research provides an innovative strategy for the treatment of AKI.