Nanoparticle Platform Research Articles

Remodeling of Mitochondrial Metabolism by a Mitochondria-Targeted RNAi Nanoplatform for Effective Cancer Therapy.

Emerging evidence has demonstrated the significant contribution of mitochondrial metabolism dysfunction to promote cancer development and progression. Aberrant expression of mitochondrial genome (mtDNA)-encoded proteins widely involves mitochondrial metabolism dysfunction, and targeted regulation of their expression can be an effective strategy for cancer therapy, which however is challenged due to the protection by the mitochondrial double membrane. Herein, a mitochondria-targeted RNAi nanoparticle (NP) platform for effective regulation of mitochondrial metabolism and breast cancer (BCa) therapy is developed. This nanoplatform is composed of a hydrophilic polyethylene glycol (PEG) shell, a hydrophobic poly(2-(diisopropylamino)ethyl methacrylate) (PDPA) core, and charged-mediated complexes of mitochondria-targeting and membrane-penetrating peptide amphiphile (MMPA) and small interfering RNA (siRNA) embedded in the core. After tumor accumulation and internalization by tumor cells, these NPs can respond to the endosomal pH to expose the MMPA/siRNA complexes, which can specifically transport siRNA into the mitochondria to down-regulate mtDNA-encoded protein expression (e.g., ATP6 and CYB). More importantly, because ATP6 down-regulation can suppress ATP production and enhance reactive oxygen species (ROS) generation to induce mitochondrial damage and mtDNA leakage into tumor tissues, the NPs can combinatorially inhibit tumor growth via suppressing ATP production and repolarizing tumor-associated macrophages (TAMs) into tumor-inhibiting M1-like macrophages by mtDNA.

MRNA Lipid Nanoparticles for Ex Vivo Engineering of Immunosuppressive T Cells for Autoimmunity Therapies.

Cell-based therapies for autoimmune diseases have gained significant traction, with several approaches centered around the regulatory T (Treg) cell─a well-known immunosuppressive cell characterized by its expression of the transcription factor Foxp3. Unfortunately, due to low numbers of Treg cells available in circulation, harvesting and culturing Treg cells remains a challenge. It has been reported that engineering Foxp3 expression in CD4+ T cells can result in a Treg-like phenotype; however, current methods result in the inefficient engineering of these cells. Here, we develop an ionizable lipid nanoparticle (LNP) platform to effectively deliver Foxp3 mRNA to CD4+ T cells. We successfully engineer CD4+ T cells into Foxp3-T (FP3T) cells that transiently exhibit an immunosuppressive phenotype and functionally suppress the proliferation of effector T cells. These results demonstrate the promise of an LNP platform for engineering immunosuppressive T cells with potential applications in autoimmunity therapies.

Pseudovirus Nanoparticles Displaying Plasmodium Circumsporozoite Proteins Elicited High Titers of Sporozoite-Binding Antibody.

malaria caused by Plasmodium parasites remains a public health threat. The circumsporozoite proteins (CSPs) of Plasmodium sporozoite play a key role in Plasmodium infection, serving as an excellent vaccine target. using a self-assembled S60 nanoparticle platform, we generated pseudovirus nanoparticles (PVNPs) displaying CSPs, named S-CSPs, for enhanced immunogenicity. purified Hisx6-tagged or tag-free S-CSPs self-assembled into PVNPs that consist of a norovirus S60 inner shell and multiple surface-displayed CSPs. The majority of the PVNPs measured ~27 nm with some size variations, and their three-dimensional structure was modeled. The PVNP-displayed CSPs retained their glycan receptor-binding function. A mouse immunization study showed that PVNPs induced a high antibody response against CSP antigens and the PVNP-immunized mouse sera stained the CSPs of Plasmodium sporozoites at high titer. the PVNP-displayed CSPs retain their authentic antigenic feature and receptor-binding function. The CSP-specific antibody elicited by the S-CSP PVNPs binds original CSPs and potentially inhibits the attachment of Plasmodium sporozoites to their host cells, a key step for liver invasion by the sporozoites. Thus, S-CSP PVNPs may be an excellent vaccine candidate against malaria caused by Plasmodium parasites.

A nanoparticle platform for combined mucosal healing and immunomodulation in inflammatory bowel disease treatment

Current treatments for inflammatory bowel disease (IBD) treatment consist of anti-inflammatory products. In this study, we sought to induce the physiological secretion of glucagon-like peptide 2, a peptide with intestinal growth-promoting activity, via nanoparticles while simultaneously providing with immunomodulation by tailoring the nanoparticle surface. To this end, we developed hybrid lipid hyaluronate-KPV conjugated nanoparticles loaded with teduglutide for combination therapy in IBD. The nanocarriers induced (or did not induce) immunosuppression depending on the presence (or absence) of a hyaluronan-KPV functionalization. This strategy holds promise as a nanoparticle platform for combined mucosal healing and immunomodulation in IBD treatment.

Hybrid LNP Prime Dendritic Cells for Nucleotide Delivery.

The efficient activation of professional antigen-presenting cells-such as dendritic cells (DC)-in tumors and lymph nodes is critical for the design of next-generation cancer vaccines and may be able to provide anti-tumor effects by itself through immune stimulation. The challenge is to stimulate these cells without causing excessive toxicity. It is hypothesized that a multi-pronged combinatorial approach to DC stimulation would allow dose reductions of innate immune receptor-stimulating TLR3 agonists while enhancing drug efficacy. Here, a hybrid lipid nanoparticle (LNP) platform is developed and tested for double-stranded RNA (polyinosinic:polycytidylic acid for TLR3 agonism) and immune modulator (L-CANDI) delivery. This study shows that the ≈120nm hybrid nanoparticles-in-nanoparticles effectively eradicate tumors by themselves and generate long-lasting, durable anti-tumor immunity in mouse models.

Engineering Metal-Phenolic Network Nanoparticles via Microfluidics.

Microfluidics opens new avenues for materials engineering, as it enables scalable synthesis and provides highly controllable environments for reactions. Herein, we leverage microfluidics to engineer the properties of (bioactive) metal-phenolic network nanoparticles (MPN NPs), an emerging and highly modular nanoparticle platform for the incorporation and delivery of bioactive cargo. By varying the microfluidics operating parameters (flow rate ratio, total flow rate, temperature) and NP composition, we assemble MPN NPs, which consist of poly(ethylene glycol), biomacromolecules, metal ions, and polyphenols. Compared to MPN NPs prepared via bulk assembly, the microfluidics-assembled MPN NPs possess a broader tunable size range (i.e., ∼40-330 nm vs ∼45-220 nm for bulk-assembled NPs) and a higher (by ∼30%) protein loading. The bulk-assembled MPN NPs show pH-responsive protein release behavior (e.g., ∼50% at pH 7; ∼25% at pH 9; 48 h). Likewise, the MPN NPs prepared via microfluidics at a flow rate ratio of 1:1 display similar pH-responsive protein release behavior. For the microfluidics-assembled MPN NPs, protein release is also dependent on temperature (e.g., 30% at 4 °C, and ∼50% at 20 and 37 °C). Furthermore, assembly at a 1:1 flow rate ratio overall enables greater tunability of protein release profiles than that at higher flow rate ratios. While bulk-assembled NPs display a higher degree of cell association, NPs assembled via both strategies can be internalized by cells after 24 h. These findings provide new insights into engineering the properties of metal-organic materials via microfluidics, which is expected to advance their development and application.

Engineering Hepatitis B Virus (HBV) Protein Particles for Therapeutic Delivery.

Nature provides an abundance of proteins whose structures and reactivity have been perfected through evolution to perform specific tasks necessary for biological function. The structural and functional properties of many natural proteins are quite valuable for the construction and customization of drug delivery vehicles. Self-assembling protein nanoparticle platforms are particularly useful scaffolds, as their multi-subunit designs allow the attachment of a high density of modifying molecules such as cell-binding ligands that provide avidity for targeting and facilitate encapsulation of large quantities of therapeutic payload. We explored SpyCatcher/SpyTag conjugation as a system to modify hepatitis B virus (HBV)-like particles (HBV VLPs). Using this simple decoration strategy, we demonstrated efficient and cell-selective killing of inflammatory breast cancer cells via delivery of yeast cytosine deaminase suicide enzymes combined with 5-fluoro-cytosine prodrugs.

Сучасні погляди на етіологію, патогенез і клінічний перебіг спонтанних передчасних пологів, тактику ведення та профілактику ускладнень (огляд літератури)

A review of medical literature regarding modern views on premature birth, the main issues of etiology and pathogenesis of this pathology, diagnostic signs, clinical features of the course, management tactics and perinatal consequences, investigated prognostic markers. A review of the medical literature regarding modern views on premature birth, the main issues of etiology and pathogenesis of this pathology, diagnostic signs, clinical features of the course, management tactics and perinatal consequences, investigated prognostic markers is provided. Despite the active and relentless development of medical science, the issue of premature births and their impact on short- and long-term consequences for mothers and children remains an urgent issue. Purpose - to highlight the scientists’ understanding of the etiology, pathogenesis, clinical management of premature birth, as well as to examine the available data on promising tocolytic drugs and methods of predicting premature birth. Among the tocolytic drugs currently undergoing clinical trials, the following groups are distinguished - broad-spectrum chemokine inhibitors, prostaglandin F2α-receptor target drugs, interleukin 1 receptor antagonists, and nanoparticle platforms. If the research is successful, obstetricians and gynecologists may have a targeted drug for the treatment of preterm labor with a better safety profile than the range of drugs we have today. Research into new laboratory prognostic markers of preterm birth, such as pregnancy-associated plasma protein A, human chorionic gonadotropin, alpha-fetoprotein, estriol, ferritin, ceruloplasmin, alkaline phosphatase, hematological markers, is also ongoing. The implementation of the above prognostic markers in clinical medicine will allow obtaining new opportunities in the early prediction of premature birth. Sonographic approaches to predicting premature birth are being updated. In addition to the measurement of the length of the cervix, the measurement of the uterine-cervical angle and the use of cervical elastography are used. Modern scientific achievements will allow doctors in the future at earlier stages of pregnancy to predict the possibility of premature birth and more effectively treat premature birth that has begun. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Revolutionizing Hyperlipidemia Treatment: Nanoencapsulated CoQ10 and Selenium Combat Simvastatin-Induced Myopathy and Insulin Resistance in Rats.

The objective of this study was to develop a nanoencapsulated platform for coenzyme Q10 nanoparticles (coQNPs) or selenium nanoparticles (SeNPs) and explore their potential therapeutic benefits in treating hyperlipidemia and combating simvastatin (SV)-induced myopathy and adverse reactions in hyperlipidemic rats. The physical and chemical properties of the solid nanoparticles, coQNPs, and SeNPs were characterized, including zeta potential studies. Male Wistar albino rats were treated with various interventions for 112 days, including a nano-vehicle only, high-fat diet (HFD), HFD with SV alone, or with coQNPs or/and SeNPs for the last 30 days. The coQNPs and SeNPs exhibited uniform spherical shapes with high encapsulation efficiency (EE% 91.20±2.14 and 94.89±1.54, respectively). The results demonstrated that coQNPs and SeNPs effectively reduced hyperlipidemia, insulin resistance, SV-induced myopathy, and hepatotoxicity. However, combining SV with coQNPs and SeNPs resulted in severe liver and muscle damage. Treatment with SV and SeNPs or SV and coQNPs alone showed significant improvements compared to SV treatment alone. These findings suggest that the CoQNPs or SeNPs platforms offer advanced relief for hyperlipidemia and insulin resistance while limiting adverse effects such as myopathy and hepatotoxicity.

Enzyme-Responsive Nanoparticles for the Targeted Delivery of an MMP Inhibitor to Acute Myocardial Infarction.

Herein, we have developed a drug-loaded matrix metalloproteinase (MMP)-responsive micellar nanoparticle (NP) intended for minimally invasive intravenous injection during the acute phase of myocardial infarction (MI) and prolonged retention in the heart for small-molecule drug delivery. Peptide-polymer amphiphiles (PPAs) bearing a small-molecule MMP inhibitor (MMPi), PD166793, were synthesized via ring-opening metathesis polymerization (ROMP) and formulated into spherical micelles by transitioning to aqueous solution. The resulting micellar NPs underwent MMP-induced aggregation, demonstrating enzyme responsiveness. Using a rat MI model, we observed that these NPs were capable of successfully extravasating into the infarcted region of the heart where they were retained due to the active, enzyme-mediated targeting, remaining detectable after 1 week post administration without increasing macrophage recruitment. Furthermore, in vitro studies show that these NPs demonstrated successful drug release following MMP treatment and maintained drug bioactivity as evidenced by comparable MMP inhibition to free MMPi. This work establishes a targeted NP platform for delivering small-molecule therapeutics to the heart after MI, opening possibilities for myocardial infarction treatment.

Multi-Stimuli-Responsive Nanoparticles Formed of POSS-PEG for the Delivery of Boronic Acid-Containing Therapeutics.

Polymeric vehicles often exhibit batch-to-batch variations due to polydispersity, limiting their reproducibility for biomedical applications. In contrast, polyhedral oligomeric silsesquioxane (POSS) has emerged as an attractive candidate for drug delivery due to its precise chemical structure and rigid molecular shape. A promising strategy to enhance drug efficacy while reducing systemic toxicity is the development of multi-stimuli-responsive delivery systems capable of targeted drug release at a disease site. Herein, we developed a drug delivery platform based on POSS-polymer conjugates. By functionalizing the POSS with amino groups and establishing B-N coordination with boronic acids, the nanoparticles (NPs) exhibit responsive behavior to stimuli, including adenosine-5'-triphosphate (ATP), acidic pH, and nucleophilic reagents. We successfully encapsulated two boronic acid-containing molecules: tetraphenylethylene (TPE), serving as a fluorescent probe, and bortezomib (BTZ), an anticancer drug. The TPE@NPs were employed to visualize the cellular uptake of NPs by tumor cells, while the BTZ@NPs exhibited increased cytotoxicity in tumor cells compared with normal cells. This POSS-PEG conjugate offers a nanoparticle platform for encapsulating versatile boronic acid-containing molecules, thereby enhancing drug efficacy while minimizing systemic toxicity. Given the wide-ranging applications of boronic acid-containing molecules in biomedicine, our platform holds significant promise for the development of intelligent drug delivery systems for diagnostics and therapeutics.

Visible Light–Near-Infrared Photodetection on Cys-MoO3−x Nanoparticles for Photothermal Therapy against Papillary Thyroid Carcinoma

The excellent performance of semiconductor nanocrystals as sensitizers for photothermal therapy (PTT) has attracted the attention of many researchers; however, they are hindered by limited bandwidth and complex synthesis. To overcome these limitations, starting with an initial determination of photothermal conductivity, we synthesized and designed molybdenum and Cys-MoO3−x nanoparticles (NPs) for use in the minimally invasive treatment of papillary thyroid carcinoma (PTC), as the NPs are coated only with cysteine molecules. The obtained Cys-MoO2 NPs were used as a PTT reaction drug for topical application to PTC cells. The use of near-infrared photoconductive PTT in combination with low-toxicity biological chemotherapy reached a 90% efficacy for cancer treatment in vitro. The conducted experiments intuitively demonstrate that non-toxic Cys-MoO2 NPs are lethal to the cancer cells under visual (VL, 405 nm) and near-infrared (NIR, 808 nm) laser irradiation and can be precisely controlled. Therefore, this study provides a powerful, safe, and easily modified NP platform for photo-triggered PTC elimination with broad application prospects. Assessment of the ideal damage range indicates a high degree of controllability, allowing the tumor to be precisely targeted while minimizing damage to the surrounding healthy tissue. In conclusion, this study provides a convenient, safe, and powerful NP platform for the near-infrared photo-controlled PTT of PTC cells, which has broad application prospects for the elimination of PTC and other types of cancer.

Ionizable Lipid Nanoparticles with Integrated Immune Checkpoint Inhibition for mRNA CAR T Cell Engineering.

The programmed cell death protein 1 (PD-1) signaling pathway is a major source of dampened T cell activity in the tumor microenvironment. While clinical approaches to inhibiting the PD-1 pathway using antibody blockade have been broadly successful, these approaches lead to widespread PD-1 suppression, increasing the risk of autoimmune reactions. This study reports the development of an ionizable lipid nanoparticle (LNP) platform for simultaneous therapeutic gene expression and RNA interference (RNAi)-mediated transient gene knockdown in T cells. In developing this platform, interesting interactions are observed between the two RNA cargoes when co-encapsulated, leading to improved expression and knockdown characteristics compared to delivering either cargo alone. This messenger RNA (mRNA)/small interfering RNA (siRNA) co-delivery platform is adopted to deliver chimeric antigen receptor (CAR) mRNA and siRNA targeting PD-1 to primary human T cells ex vivo and strong CAR expression and PD-1 knockdown are observed without apparent changes to overall T cell activation state. This delivery platform shows great promise for transient immune gene modulation for a number of immunoengineering applications, including the development of improved cancerimmunotherapies.

Liposomal co-delivery of toll-like receptors 3 and 7 agonists induce a hot triple-negative breast cancer immune environment

Triple-negative breast cancer (TNBC) is highly aggressive and has no standard treatment. Although being considered as an alternative to conventional treatments for TNBC, immunotherapy has to deal with many challenges that hinder its efficacy, particularly the poor immunogenic condition of the tumor microenvironment (TME). Herein, we designed a liposomal nanoparticle (LN) platform that delivers simultaneously toll-like receptor 7 (imiquimod, IQ) and toll-like receptor 3 (poly(I:C), IC) agonists to take advantage of the different toll-like receptor (TLR) signaling pathways, which enhances the condition of TME from a “cold” to a “hot” immunogenic state. The optimized IQ/IC-loaded LN (IQ/IC-LN) was effectively internalized by cancer cells, macrophages, and dendritic cells, followed by the release of the delivered drugs and subsequent stimulation of the TLR3 and TLR7 signaling pathways. This stimulation encouraged the secretion of type I interferon (IFN-α, IFN-β) and CXCLl0, a T-cell and antigen-presenting cells (APCs) recruitment chemokine, from both cancer cells and macrophages and polarized macrophages to the M1 subtype in in vitro studies. Notably, systemic administration of IQ/IC-LN allowed for the high accumulation of drug content in the tumor, followed by the effective uptake by immune cells in the TME. IQ/IC-LN treatment comprehensively enhanced the immunogenic condition in the TME, which robustly inhibited tumor growth in tumor-bearing mice. Furthermore, synergistic antitumor efficacy was obtained when the IQ/IC-LN-induced immunogenic state in TME was combined with anti-PD1 antibody therapy. Thus, our results suggest the potential of combining 2 TLR agonists to reform the TME from a “cold” to a “hot” state, supporting the therapeutic efficacy of immune checkpoint inhibitors.

Nanoparticle platform comprising lipid-tailed pH-sensitive carbon dots with minimal drug loss

Herein, we synthesized a lipid-mimicking organic material (PCD_FA) that can surpass the efficacy of lipid-based nanoparticles and demonstrated its potential as a delivery vehicle for various hydrophilic drugs. PCD_FA is a conjugate of pH-sensitive carbon dots (PCDs) and fatty acids (FAs) and has potential applications in several fields owing to various combinations of carbon dots (CDs) and FAs. Similar to phospholipids, PCD-FAs have hydrophilic heads and hydrophobic tails that allow them to self-form nanoparticles (Coposomes) in the aqueous phase. Coposomes can easily combine various hydrophilic head and hydrophobic tail combinations, and several drugs can be encapsulated, or drug release patterns can be controlled according to each property. We analyzed the differences in size, drug loading efficiency, and drug release patterns of Coposomes depending on the type of FAs and characteristics of the encapsulated drugs. Additionally, cell entry and intracellular drug release mechanisms of the Coposomes were identified. The applicability of Coposomes as drug delivery carriers for tumor treatment has been demonstrated in comparison with that of liposomes formulation in tumor-bearing mouse models. Consequently, this study presents possibilities for the synthesis and application of various amphiphilic lipid-mimicking organic materials via the combination of CDs and FAs with various functions.

Super-assembly platform for diverse nanoparticles with tunable topological architectures and surface morphologies

Self-assembly leveraged by nature enables the sophisticated generation of a wide range of nanoparticles (NPs) with rich architectures and morphologies. However, existing artificial self-assembly platforms largely only allow for the fabrication of single type of NPs with limited structures, due to their inability to define interfacial interaction between seeds and growth materials, which is critically important to gain controllable growth patterns of the grown materials on the seeds’ surface. Here, we report a versatile super-assembly platform that shows the capabilities to fabricate diverse NPs with tunable topological architectures and surface morphologies, e.g., molecular-like NPs, hollow asymmetric NPs, patchy NPs, etc. We unprecedentedly discovered the powerful functions of polyvinylpyrrolidone (PVP), which enable us to well define interfacial interaction between growth materials and seeds to achieve the controllable and tunable generation of various complex topological growth patterns. Moreover, the nucleation pattern (island nucleation or layered nucleation) of the patches can be thermodynamically modulated via the polarity of the solvent, while the number and size of the patches can be kinetically tuned by the ratio of polystyrene (PS), precursor, and catalyst. Interestingly, the hollow NPs can be generated by single-one processing step in our platform, unlike the multiple steps laboriously and widely employed by previously reported fabrication platforms. In addition, we demonstrate that our annealed NPs can not only selectively reflect visible light, and show well-controlled colors from gray, blue, to green, but also exhibit excellent photothermal conversion performances with a high photothermal conversion efficiency of 68.7% that are superior to currently routinely reported of 40%. This super-assembly platform can serve as a powerful toolset to sophisticatedly create varied NPs with tunable hierarchical architectures and controllable surface morphologies, which would significantly benefit the development of drug delivery, nanomaterial assembly, nano pigments, nanoreactors, and beyond.

An electrochemical immunosensor on a carbon nanofiber/gold nanoparticles platform for the detection of alpha-feto protein cancer biomarker

We report an alpha – fetoprotein (AFP) cancer biomarker electrochemical immunosensor detected on a carbon nanofiber (CNF) and gold nanoparticles (AuNPs) platform. Functionalised carbon nanofiber and gold nanoparticles were immobilised through drop drying and electrodeposition techniques respectively on a glassy carbon electrode (GCE). AFP antibody was immobilised on the platform overnight followed by blocking of nonspecific binding sites with bovine serum albumin (BSA) for 4 h. The AFP antigen was incubated on the platform for 40 min at 35 °C for the antigen – antibody interaction. CNF and AuNPs were characterised by electron microscopy and Fourier transform infrared (FTIR) spectroscopy. The modified electrodes and the immunosensor were characterised by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) techniques. The electrochemical response of the GCE/CNF/AuNPs electrode and the resulting immunosensor was significantly enhanced by the nanocomposite of CNF and AuNPs. The electrochemical immunosensing measurement for AFP was carried out under optimal conditions at a concentration range from 0.005 to 500 ng mL−1 in 5 mM ferri/ferrocyanide solution. A low limit of detection of 0.50 pg mL−1 from square wave voltammetry (SWV) and 0.48 pg mL−1 from EIS measurements were obtained. The immunosensor exhibited good sensitivity, good selectivity, good repeatability, and was stable at 4 °C over a period of three weeks.

Nanoparticles (NPs)-mediated lncBCMA silencing to promote eEF1A1 ubiquitination and suppress breast cancer growth and metastasis.

Long non-coding RNAs (lncRNAs) play an important role in cancer metastasis. Exploring metastasis-associated lncRNAs and developing effective strategy for targeted regulation of lncRNA function invivo are of utmost importance for the treatment of metastatic cancer, which however remains a big challenge. Herein, we identified a new functional lncRNA (denoted lncBCMA), which could stabilize the expression of eukaryotic translation elongation factor 1A1 (eEF1A1) via antagonizing its ubiquitination to promote triple-negative breast cancer (TNBC) growth and metastasis. Based on this regulatory mechanism, an endosomal pH-responsive nanoparticle (NP) platform was engineered for systemic lncBCMA siRNA (siBCMA) delivery. This NPs-mediated siBCMA delivery could effectively silence lncBCMA expression and promote eEF1A1 ubiquitination, thereby leading to a significant inhibition of TNBC tumor growth and metastasis. These findings show that lncBCMA could be used as a potential biomarker to predict the prognosis of TNBC patients and NPs-mediated lncBCMA silencing could be an effective strategy for metastatic TNBC treatment.

One pot preparation of muti-mode nanoplatform to combat ovarian cancer

Ovarian cancer is one of the most common gynecological cancers with high mortality rate. The battle against ovarian cancer usually impaired by the evolved multidrug resistance (MDR) phenotype as well as metastasis in cancers, which urgently call for the development of multi-mode strategies to overcome the MDR and reduce metastasis. Considering the good benefits of ferroptosis and photothermal therapy (PTT) in cancer management, we herein proposed a facile way to construct nanoparticle platform (Fe-Dox/PVP) composed of ferric chloride, doxorubicin (Dox) and polyvinyl pyrrolidone (PVP) for the multi-mode therapy of ovarian cancer using chemotherapy, ferroptosis and mild hypothermia PTT. Our results demonstrated that Fe-Dox/PVP with mild hypothermia was shown to have improved endosomal escape/drug delivery, enhanced ferroptosis induction and good tumor targeting effects. Most importantly, the integration of all three effects into one platform provided increased anti-metastasis effect and promising in vitro/in vivo anticancer performance with high biocompatibility. In this study, we offer a facile and robust way to prepare a multi-mode nanoplatform to combat ovarian cancer, which can be further extended for the management of many other cancers.

Synthesis and Optimization of the Docetaxel-Loaded and Durvalumab-Targeted Human Serum Albumin Nanoparticles, In Vitro Characterization on Triple-Negative Breast Cancer Cells.

Triple-negative breast cancer (TNBC) tends to behave more aggressively compared to other breast cancer subtypes due to the lack of receptors and its limited targeting therapy. In recent years, nanotechnology advancement has led to the development of various nanoparticle platforms for the targeted treatment of cancers. Especially, HSA-NPs have specific advantages such as biocompatibility, adjustable size during production, and relatively easy synthesis. In this study, HSA-NPs were encapsulated with docetaxel (DTX) and functionalized with polyethylene glycol (PEG), also becoming a targeting nanoplatform modified with durvalumab (DVL), and the whole nanostructure was well characterized. Subsequently, drug release studies and various in vitro cell culture studies such as determining the cytotoxicity and apoptotic levels of the nanoplatforms and PD-L1 using ELISA test were conducted on MDA-MB-468, MDA-MB-231, and MCF-7 cells. According to the results, HSA-DTX@PEG-DVL NPs showed better cytotoxicity compared to DTX in all the three cell lines. In addition, it was observed that the HSA-DTX@PEG-DVL NPs did not lead the cells to late apoptosis but were effective in the early apoptotic stage. Moreover, the ELISA data showed a significantly induced PD-L1 expression due to the presence of DVL in the nanostructure, which indicates that DVL antibodies successfully bind to the HSA-DTX@PEG-DVL nanostructure.