Glioma is the most prevalent type of primary brain tumor, and glioblastoma multiforme (GBM) is the highest and most deadly type of primary central nervous system (CNS) tumor, affecting a significant number of patients each year, with a median overall survival of approximately 14.6 months after diagnosis. Despite intensive treatment, nearly all GBM patients experience recurrence, with a 5-year survival rate of about 5%. The protective BBB and high tumor heterogeneity prevent the effective delivery of drugs, resulting in the treatment failure of various drugs. The emergence of nanometer-scale diagnosis and treatment methods has provided new promising approaches to overcome these difficulties. Thus, our review focuses on the development of BBB-crossing nanomedicine-enhanced chemotherapy and combined therapy applications for glioma. Meanwhile, we also reviewed the strategies to overcome the blood–brain barrier. Additionally, we discuss recent achievements in the area of brain tumor treatment with nanomedicine and the rational design approach, which will offer recommendations for anti-GBM nanomedicine development.

The lack of efficacious treatments for clear cell renal cell carcinoma (ccRCC) has led to a poor 5-year survival rate. Here, we found that the expression of ADAM metallopeptidase with thrombospondin type 1 motif 9 (ADAMTS9) antisense RNA 1 (ADAMTS9-AS1) is commonly decreased in ccRCC tissues. Decreased ADAMTS9-AS1 is associated with advanced stages and poor prognosis in ccRCC patients. Additionally, we found that promoter hypermethylation contributes to the suppression of ADAMTS9-AS1 expression in ccRCC that contained relatively low levels of ADAMTS9-AS1. Further functional studies demonstrated that ADAMTS9-AS1 inhibits cell growth and drug resistance through enhancing mRNA stability of ADAMTS9 in ccRCC. Mechanistically, ADAMTS9-AS1 directly bound to Human Antigen R (HuR). Then, the ADAMTS9-AS1-HuR complex was guided to the ADAMTS9 3’UTR through specific RNA–RNA interaction. Moreover, ADAMTS9-AS1 expression is positively correlated with ADAMTS9 expression in ccRCC tissues. In summary, our data not only highlight the important role of ADAMTS9-AS1 in ccRCC progression, but also reveal new regulatory mechanisms of ADAMTS9, which provides important insights into novel treatment strategies targeting ADAMTS9-AS1-HuR- ADAMTS9 axis in ccRCC.

Ti3C2 is a type of transition metal carbides and nitrides (MXenes) with high light-to-heat conversion efficiency property, which has been widely used in cancer treatment recently. In fact, active targeting delivery of MXenes nanomaterials with targeting molecule could enhance the therapeutic efficacy. However, targeted therapy of MXenes has not been further studied in the past. Aptamers (Apt) with excellent affinity and high specificity properties have been widely used as targeting tools. Predictably, the incorporation of Apt into Ti3C2 nanomaterials will offer an unprecedented opportunity in the research fields of cancer targeted therapy. Transmembrane glycoprotein mucin 1 (MUC1) is overexpressed on the surface of MCF-7 cells, and MUC1 Apt (Apt-M) could target MCF-7 cells with high affinity and specificity. Here, a smart targeting nanotherapeutic system Ti3C2/Apt-M was fabricated, which could specifically recognize and enter in MCF-7 cells. Benefitting from the desirable targeted performance of Apt-M, MCF-7 cells completed the ingestion process of Ti3C2/Apt-Mf nanosheets within 4 h, and Apt-M facilitated the entry of the Ti3C2/Apt-Mf nanosheets into MCF-7 cells. Besides, Ti3C2/Apt-M nanosheets exhibited the potential as an outstanding photothermal agent (PTA) because of the photothermal performance inherited from wrapped Ti3C2 nanosheets. As demonstrated, upon 808 nm laser irradiation, the Ti3C2/Apt-M nanotherapeutic system displayed a satisfactory antitumor effect by targeted photothermal therapy both in vitro and in vivo. This study provides a new idea for the development of MXenes nanotherapeutic system with high active targeting performance.

Cationic dyes are widely used as biomarkers for optical imaging. However, most of these are hydrophobic and cannot be employed in vivo without chemical conjugation or modification. Herein, we report for the first time the use of bacterial outer membrane vesicles (OMVs) as nanocarriers of cationic dyes for cancer theranostics. We demonstrate that cationic dyes (IR780, Cy7, and Cy7.5) form stable complexes with negatively charged bacterial-OMVs, improving the dyes’ in vivo circulation and optoacoustic properties. Such OMV-Dye complexes are biodegradable and safe for in vivo applications. Importantly, this method of cationic dye loading is faster and easier than synthetic chemistry approaches, and the efficient tumor accumulation of OMV-Dyes enables sensitive tumor detection using optoacoustic technology. As a proof-of-concept, we generated OMV-IR780 for optoacoustics-guided in vivo tumor phototherapy in a mouse model. Our results demonstrate cationic dye-bound OMVs as promising novel nanoagents for tumor theranostics.

Gadolinium-based nanoparticles (GdNPs) are clinically used agents to increase the radiosensitivity of tumor cells. However, studies on the mechanisms and biological modeling of GdNP radio-enhancement are still preliminary. This study aims to investigate the mechanism of radio-enhancement of GdNPs for kilovoltage photons using Monte Carlo (MC) simulations, and to establish local effect model (LEM)-based biological model of GdNP radiosensitization. The spectrum and yield of secondary electrons and dose enhancement around a single GdNP and clustered GdNPs were calculated in a water cube phantom by MC track-structure simulations using TOPAS code. We constructed a partial shell-like cell geometry model of pancreatic cancer cell based on transmission electron microscope (TEM) observations. LEM-based biological modeling of GdNP radiosensitization was established based on the MC-calculated nano-scale dose distributions in the cell model to predict the cell surviving fractions after irradiation. The yield of secondary electrons for GdNP was 0.16% of the yield for gold nanoparticle (GNP), whereas the average electron energy was 12% higher. The majority of the dose enhancement came from the contribution of Auger electrons. GdNP clusters had a larger range and extent of dose enhancement than single GdNPs, although GdNP clustering reduced radial dose per interacting photon significantly. For the dose range between 0 and 8 Gy, the surviving fraction predicted using LEM-based biological model laid within one standard deviation of the published experimental results, and the deviations between them were all within 25%. The mechanism of radio-enhancement of GdNPs for kilovoltage photons was investigated using MC simulations. The prediction results of the established LEM-based biological model for GdNP radiosensitization showed good agreement with published experimental results, although the deviation of simulation parameters can lead to large disparity in the results. To our knowledge, this was the first LEM-based biological model for GdNP radiosensitization.

Intraperitoneal metastasis is one of the major causes of the high mortality rate of ovarian cancer. Bufalin (BU) is an effective component of the traditional Chinese medicine Chansu that exerts antitumor effects, including metastasis inhibition. In our previous studies, we found that BU inhibited the migration and invasion of ovarian cancer cells. However, the application of BU is limited due to its insolubility, toxicity and imprecise targeting. The aim of this study was to use vitamin E succinate (VES)-grafted chitosan oligosaccharide (CSO)/arginine-glycine-aspartic acid peptide (RGD)-conjugated d-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) mixed micelles (VeC/T-RGD MMs) to deliver BU to ovarian cancer cells to inhibit intraperitoneal metastasis. Moreover, the toxicity of BU was reduced by coating it with the mixed micelles to increase its biocompatibility for practical applications. The BU-loaded VeC/T-RGD MMs (BU@MMs) had an average diameter of 161 ± 1.4 nm, a zeta potential of 4.49 ± 1.54 mV and a loading efficiency of 2.54%. The results showed that these micelles inhibited cell proliferation, induced apoptosis, and reduced the migration and invasion of A2780 and SKOV3 cells. Further studies indicated that BU@MMs enhanced the levels of e-cadherin and decreased the expression levels of N-cadherin, vimentin and Snail in vitro. In addition, the mixed micelles effectively enhanced the anticancer effect and inhibited intraperitoneal metastasis in intraperitoneal metastatic models. The BU@MMs exhibited fewer toxic side effects than BU, indicating better biocompatibility and biosafety for in vivo applications. Our studies show that BU@MMs are a potential multifunctional nano-drug delivery system that can effectively inhibit the intraperitoneal metastasis of ovarian cancer.

Cancer treatment by inducing tumor cell immunogenic cell death (ICD) is critical for tumor therapy. However, ICD activation by single pathway is often limited in practical application due to its low efficiency. In addition, the low pH and anoxic microenvironments in solid tumors greatly limit the effective activation of ICD. Herein, hollow manganese dioxide (H-MnO2) nanomaterials were selected to load both Mitoxantrone (MTZ) and Chlorin e6 (Ce6) due to its hollow structure and ability to release drugs in the acidic environments. Thus, the synergy of photodynamic therapy (PDT), photothermal therapy (PTT) and chemotherapy can induce the process of immunogenic cell death, stimulate the maturation of dendritic cells (DCs), and activate the immune response to kill tumor cells dramatically. Efficient immunotherapeutic effects were obtained when MnO2-C/M-HA was given intravenously to 4T1 tumor-bearing BALB/c mice with 660 nm near-infrared laser irradiation. This study overcame the limitations of monotherapy and provided a multifunctional platform for tumor immunotherapy.

Overwhelming Fe accumulation in tumor arouses strong oxidative stress. To benefit the cancer patients, Fe(II) delivered by carbon nanoparticles-Fe(II) complex (CNSI-Fe) should be visualized to ensure the successful intratumoral injection and the antitumor mechanisms should be investigated at molecular level. Intracellular Fe accumulations associating with the uptakes of CNSI-Fe were observed both in vitro and in vivo. The retention of Fe(II) in tumor over 72 h was visualized by magnetic resonance imaging. CNSI-Fe inhibited the tumor growth and expanded the lifespan of colonic tumor-bearing mice. The antitumor activity of CNSI-Fe was attributed to the increases of OH radicals and the oxidative stress in tumor cells, which resulted in cell apoptosis and ferroptosis. The transcriptome analyses confirmed the changes of ferroptosis and inflammation signaling pathways by CNSI-Fe treatment. The low toxicity of CNSI-Fe was indicated by the serum biochemistry, hematology, and histopathology. CNSI-Fe induced the efficient apoptosis and ferroptosis of colonic tumor for cancer therapy. Our results would benefit the clinical applications of CNSI-Fe and stimulate great interest in the nanomedicine.

Developing high-performance sensing frameworks for diagnosing anaplastic changes is the subject of debate. The lack of on-time diagnosis in patients with suspicious cancers can affect the prognosis and survival rate. As a correlate, the emergence of de novo strategies for developing transducing frameworks has an inevitable role in advanced biosensing. The combination of green chemistry procedures with eco-friendly and biocompatible materials is of high desirability in this context. The synthesis of new biocompatible and cost-effective nanomaterials to meet the emerging needs of rising demands appeals to new synthetic methodologies. Here, we applied the electrochemical synthesis method to the fabrication of biocompatible and subtly governed Molybdenum trioxide/poly taurine nano-bio films to monitor human epidermal growth factor receptor-2 (HER-2) in sera from breast cancer patients. Morphological and elemental assessments were performed using a scanning electron microscope, energy-dispersive X-Ray spectroscopy, and dot mapping analyses. In addition, HER-2 immunohistochemistry (IHC) staining was performed on tissue samples, and data were compared to the values obtained by Molybdenum trioxide/poly taurine nano-bio films. We also noted our platform is eligible for feasible, rapid, and specific determination of HER-2 factor in human samples. The method had a lower limit of quantification of 0.000001 ng/mL and a linear dynamic range between 0.1 ng/mL and 0.000001 ng/mL. IHC imaging showed that the degree of anaplastic changes in breast samples (intensity of HER-2 factor) was closely associated with the intensity of signals obtained by our developed immunosensor. According to the obtained desirable coordination with pathological studies, the designed biosensor has excellent capability to use as a reliable diagnostic tool in clinical laboratories.

The presented research concerns the preparation of polymer nanoparticles (PNPs) for the delivery of doxorubicin. Several block and statistical copolymers, composed of ketoester derivative, N-isopropylacrylamide, and cholesterol, were synthesized. In the nanoprecipitation process, doxorubicin (DOX) molecules were kept in spatial polymeric systems. DOX-loaded PNPs show high efficacy against estrogen-dependent MCF-7 breast cancer cell lines despite low doses of DOX applied and good compatibility with normal cells. Research confirms the effect of PNPs on the degradation of the biological membrane, and the accumulation of reactive oxygen species (ROS), and the ability to cell cycle arrest are strictly linked to cell death.

Ferroptosis represents an innovative strategy to overcome the resistance of traditional cancer therapeutic through lethal lipid peroxidation leading to immunogenic cell death. However, the inefficiency of ferroptosis inducers and mild immunogenicity restrict the further clinical applications. Herein, engineering exosome-mimic M1 nanovesicles (MNV) were prepared by serial extrusion of M1 macrophage and served as an efficient vehicle for docosahexaenoic acid (DHA) delivery. MNV loaded with DHA (MNV@DHA) could promote more DHA accumulation in tumor cells, depletion glutathione and reduction of lipid antioxidant glutathione peroxidase-4 facilitating the occurrence of ferroptosis. Furthermore, MNV were able to induce the polarization of M1 and repolarize M2 macrophages to activate tumor immune microenvironments. The activated immune cells would further trigger the ferroptosis of tumor cells. In a murine orthotopic hepatocellular carcinoma model, MNV@DHA could significantly target tumor tissues, increase the proportion of M1 macrophages and CD8+ T cells and lessen the infiltration of M2 macrophages. Accordingly, MNV@DHA characterized with positive feedback regulation between ferroptosis and immune activation exhibited the strongest in vivo therapeutic effect. The synergism of ferroptosis and immunomodulation based on the dietary polyunsaturated fatty acids and engineered exosome-mimic nanovesicles may serve as a promising modality to efficiently complement pharmacological approaches for cancer management.

Using a chemotherapeutic agent, such as doxorubicin (DOX), with a natural agent, such as silibinin (Sili), is highly valuable to minimize systemic toxicity. However, Sili and DOX face disadvantages, such as low aqueous solubility and poor bioavailability. Here, we have engineered a drug delivery cargo by decorating carboxylated graphene oxide (cGO) with an aptamer, HB5, for simultaneous delivery of DOX and Sili as a combination therapy against MCF-7 and SK-BR-3 breast cancer cells. The resulting Apt-cGO displayed a typical sheet-like nanostructure with a broad surface. The maximum entrapment efficiency was 70.42% and 84.22% for Sili and DOX, respectively. When the Apt-cGO-DOX-Sili nanocomposites were selectively taken up by breast cancer cells, the interaction between cGO and drugs was cleaved, causing releasing both Sili and DOX into the tumor cells, respectively. Compared to free drugs, Apt-cGO-DOX-Sili nanocomposites displayed higher cytotoxicity in vitro. Apt-cGO-DOX-Sili nanocomposites potentially suppressed some cancer cell survival signals. They accelerated cell apoptosis and increased Rb levels as well as reduced Akt, mTOR, NF-κB, and CDK2 levels. In conclusion, the developed Apt-cGO-DOX-Sili can be suggested as a simple and efficient drug delivery approach for breast chemotherapy.

Combining the power of magnetic guidance and the biological activities of stem cells transformed into biohybrid microrobots holds great promise for the treatment of several diseases including cancer. We found that human MSCs can be readily loaded with magnetic particles and that the resulting biohybrid microrobots could be guided by a rotating magnetic field. Rotating magnetic fields have the potential to be applied in the human setting and steer therapeutic stem cells to the desired sites of action in the body. We could demonstrate that the required loading of magnetic particles into stem cells is compatible with their biological activities. We examined this issue with a particular focus on the expression and functionality of therapeutic genes inside of human MSC-based biohybrid microrobots. The loading with magnetic particles did not cause a loss of viability or apoptosis in the human MSCs nor did it impact on the therapeutic gene expression from the cells. Furthermore, the therapeutic effect of the gene products was not affected, and the cells also did not lose their migration potential. These results demonstrate that the fabrication of guidable MSC-based biohybrid microrobots is compatible with their biological and therapeutic functions. Thus, MSC-based biohybrid microrobots represent a novel way of delivering gene therapies to tumours as well as in the context of other diseases.

Anethole (Ant) is a herbal compound with unique properties, which is limited in its clinical use due to its low solubility in aqueous solutions. Therefore, in this study, albumin nanocarrier modified with chitosan-folate was used to transfer Ant to cancer cells and its anticancer effects were evaluated. First, Ant was loaded on albumin nanoparticles by desolvation method and then the surface of nanoparticles was covered with chitosan bound to folate. After characterization, the amount of Ant loading in nanoparticles was measured by the absorption method and then its toxicity effects on breast cancer cell lines, colon, and normal cells were evaluated by the MTT method. The real-time QPCR method was used to investigate the expression changes of apoptosis-related genes in the treated cells compared to the control cells, and finally, the antitumor effects of nanoparticles were evaluated in the mouse model carrying breast cancer. The results of this investigation showed the presence of nanoparticles with dimensions of 252 nm, a dispersion index of 0.28 mV, and a surface charge of 27.14 mV, which are trapped in about 88% of ATL. The toxicity effect of nanoparticles was shown on breast, colon, and normal cancer cells, respectively. In addition, the examination of the gene profile under investigation showed an increase in the expression of BAX and caspase-3 and -9 along with a decrease in the expression of the Bcl-2 gene, which confirms the activation of the internal pathway of apoptosis. The decrease in the volume of tumors and the presence of apoptotic areas in the tissue sections confirmed the antitumor effects of nanoparticles in the in vivo model. The inhibition percentage of free Ant and nanoparticles with a concentration of 25 and 50 mg/kg/tumor volume was reported as 36.9%, 56.6%, and 64.9%, respectively, during 15 days of treatment. These results showed the effectiveness of the formulation in inhibiting cancer cells both in vitro and in vivo.

Tumor microparticles (T-MPs) are considered as a tumor vaccine candidate. Although some studies have analyzed the mechanism of T-MPs as tumor vaccine, we still lack understanding of how T-MPs stimulate a strong anti-tumor immune response. Here, we show that T-MPs induce macrophages to release a key chemotactic factor CCL2, which attracts monocytes to the vaccine injection site and enhances endocytosis of antigen. Monocytes subsequently enter the draining lymph node, and differentiate into monocyte-derived DCs (moDCs), which present tumor antigens to T lymphocytes and deliver a potent anti-tumor immune response. Mechanically, T-MPs activate the cGAS-STING signaling through DNA fragments, and then induce monocytes to upregulate the expression of IRF4, which is a key factor for monocyte differentiation into moDCs. More importantly, monocytes that have endocytosed T-MPs acquire the ability to treat tumors. Collectively, this work might provide novel vaccination strategy for the development of tumor vaccines and facilitate the application of T-MPs for clinic oncotherapy.

Chlorin e6 trisodium salt (Ce6) is a newly developed hydrophilic photosensitizer designed to mediate anticancer photodynamic therapy (PDT). The response of different cancer types and strategies to boost anticancer efficiency of Ce6-PDT are poorly studied. This study aimed to investigate the response of different cancer types to Ce6-PDT, identify the unresponsive ones, and develop a nanosystem for response enhancement. Sk-Br-3, MCF-7, U87, and HF-5 cells were tested in 2D cell cultures. Ce6 uptake, PDT-mediated phototoxicity, ROS production, caspase 3/7 levels, and cell death mode were examined. Furthermore, U87 spheroids were treated with Ce6-PDT. Mesoporous silica nanoparticles (MSN) were synthesized and loaded with Ce6. Cellular uptake and phototoxicity of MSN-Ce6 were compared to free Ce6 in vitro and in vivo. Ce6 was detectable in the cell cytoplasm within 15 min. U87 cells showed the highest Ce6 cellular uptake. Upon Ce6-PDT, U87 cells were the most responsive ones with an 11-fold increase in ROS production. Here, 5 µM Ce6 and 4 J/cm2 were enough to reach IC50. Ce6-PDT induced both necrotic and caspase-dependent apoptotic cell death and 75% reduction of spheroids volume. Also, MCF-7 and HF-5 cells responded well to Ce6-PDT treatment. Sk-Br-3 breast cancer cells, on the other hand, were the least responsive ones with 80% viability after treatment (5 µM Ce6, 8 J/cm2). However, MSN-Ce6 conjugates increased Sk-Br-3 cellular uptake of Ce6 sevenfold decreasing the IC50 irradiation dose by an order of magnitude. In a very aggressive breast cancer rat model, MSN-Ce6-PDT treatment led to suppression of tumor volume by 50% and elevation of both Bax and caspase 3 by 90% compared to the control while the corresponding values for Ce6-PDT were 30% and 70%, respectively. The newly developed hydrophilic chlorin and even more its MSN conjugate show high activities in anticancer PDT.

The accurate diagnosis and treatment of cancer cell lesions need a high standard of detection technology. Fluorescent probes to perform cancer biomarker detection have become a popular research issue. However, fluorescent probes still face enormous challenges of complex design and difficult detection. In this work, we propose a novel composite material UCNP@SiO2 + QDs based on the combination of rare earth upconversion (UCNPs) and perovskite quantum dots (QDs) and design a new fluorescent probe MB-UCNP@SiO2 + QDs with molecular beacon (MB) as the carrier, that can be excited by near-infrared light, emitted in the visible wavelength, specifically identified and highly sensitive. Under the excitation of 980 nm near-infrared light, the UCNPs and QDs in the composite produced the maximum efficiency of energy transfer through fluorescence resonance, and the multi-emission light of UCNPs synergistically excited the re-emission of QDs, and the energy transfer efficiency is 70.6%. By changing the doping ratio of QDs halogen elements in UCNP@SiO2 + QDs, it is possible to modulate the precise luminescence of UCNP@SiO2 + QDs in the entire wavelength range of visible light at different positions. The novel fluorescent probe is obtained using UCNP@SiO2 + QDs and Black Hole Quencher-1 (BHQ1) quenching groups linked to the two respective sides of MB, selecting as the target of detection the myeloma cancer biomarker miRNA-155, a difficult diagnostic and complex developmental type, and have achieved specific recognition and low concentration of miRNA-155 and a detection limit of 73.5 pM. This fluorescent probe design can provide new ideas for the early diagnosis and treatment of cancer, tumors, and cardiovascular diseases.

Increasing evidence indicates that radiotherapy (RT) has synergistic inhibitory efficiency with immunotherapy agents in multiple cancers and enhances abscopal effects by regulating the innate immune response, which was further investigated in this study. Neutrophils are recruited in radiated tumors. Therefore, neutrophil membrane-coated nanoparticles potentially deliver R837 (Toll-like receptor 7 agonist) to radiated tumors. A novel nanoparticle R837@PLGA@Neu was prepared by initially assembling PLGA (poly (lactic-co-glycolic acid)) with R837 (TLR7 agonist) into R837@PLGA followed by coating with neutrophil membrane. Characterizations of R837@PLGA@Neu were performed. Tumor targeting efficiency was evaluated by in vivo fluorescent imaging of CT26-bearing mice. Treatments of R837@PLGA@Neu combined with RT were carried out in unilateral and bilateral CRC tumor-bearing mice, followed by validations of immune cells in tumors by flow cytometry. The characteristics of R837@PLGA@Neu were well identified, and it was confirmed to have high uptake ability and low cytotoxicity in colorectal cancer (CRC) cells in vitro, as well as its strong tumor-targeting efficiency in vivo in CRC tumor-bearing mice. The exciting findings were that R837@PLGA@Neu combined with RT exerted prominent tumor inhibition not only in radiated tumors, but also in distant tumors without RT, suggesting its enhancement of the efficacy and abscopal effect of RT. The possible underlying mechanisms were remodeling of the tumor microenvironment by triggering mature dendritic cells and CD8+ T cells. In summary, our findings suggested that neutrophil membrane-derived nanoparticle R837@PLGA@Neu with high uptake ability and low cytotoxicity showed strong tumor-targeting efficiency, and combination with RT had a promising effect in CT26-bearing mice via immune cell regulation. Our results provide a probable combination strategy for CRC treatment.

Tumor angiogenesis, immunosuppression, and progression are all closely correlated with the tumor microenvironment (TME). Immune evasion is supported by both M2 phenotype tumor-associated macrophages (TAMs) and vascular aberrations in the TME. TME reprogramming is a promising therapeutic approach for treating tumors. Anti-angiogenesis has the power to control the polarization of macrophages, prevent progression, and increase drug penetration. Additionally, polyamine blocking therapy can increase CD8+ T cell infiltration and decrease immunosuppressive cells. These results led to developing a potential therapeutic regimen that targets TAMs and angiogenesis to reprogram the osteosarcoma TME. For the targeted biomimetic co-delivery of regorafenib and alpha-difluoromethylornithine via the mannose receptor, which is overexpressed in both TAMs and osteosarcoma cells, mannosylated poly(lactide-co-glycolide)-polyethylene glycol nanoparticles (Man-NPs) were synthesized. The superior physiological properties and intratumoral accumulation of the Man-NPs efficiently promoted TAMs polarization and inhibited angiogenesis. Macrophage repolarization further activated immune cells, which contributed to remodeling the TME. Overall, these findings suggested that using Man-NPs as an immunotherapeutic approach to treat osteosarcoma may be promising.

The study’s goal was to look into the protective properties of quercetin (QU) in natural form and QU nanoparticles-loaded chitosan nanoparticles (QU-CHSNPs) against cardiotoxicity. The ionotropic gelation approach was adopted to form QU-CHSNPs. The characterizations were performed using advanced techniques. In vitro, the release profile of QU was studied. Cardiotoxicity was induced by doxorubicin (DOX) and protected via concurrent administration of QU and QU-CHSNPs. The heart's preventive effects of QU and QU-CHSNPs were manifested by a decrease in elevated serum activities of cardiac enzymes, as well as an improvement in the heart's antioxidant defence system and histological changes. The findings substantiated QU-CHSNPs' structure with an entrapment efficiency of 92.56%. The mean of the zeta size distribution was 150 nm, the real average particle size was 50 nm, and the zeta potential value was − 27.9 mV, exhibiting low physical stability. The percent of the free QU-cumulative release was about 70% after 12 h, and QU-CHSNPs showed a 49% continued release with a pattern of sustained release, reaching 98% after 48 h. And as such, QU and QU-CHSNPs restrained the induced cardiotoxicity of DOX in male Wistar rats, with the QU-CHSNPs being more efficient.