Albumin Nanoparticles Research Articles

A nanoparticle composed of totally hospital-available drugs and isotope for fluorescence/SPECT dual-modal imaging-guided photothermal therapy to inhibit tumor metastasis

As primary sites of tumor metastasis, sentinel lymph nodes (SLNs) require a highly biocompatible theranostic platform for precise localization and treatment to inhibit tumor metastasis. Herein, indocyanine green-human serum albumin (ICG-HSA) nanoparticles (NPs) were fabricated by ICG-induced self-assembly and radiolabeled with technetuim-99 m (99mTc). The fabricated NPs were composed of hospital-available drugs and isotopes, making them highly biocompatible for in vivo applications. In a mouse model of SLN metastasis, the prepared NPs exhibited excellent capacity for preoperative planning by single-photon emission computed tomography (SPECT) imaging-enabled SLN localization, near-infrared fluorescence (NIRF) imaging-enabled intraoperative real-time monitoring, and SLN photothermal treatment. Photothermal treatment with SLN enhanced the inhibition of lung metastasis and significantly increased the survival time of mice. The prepared NPs were highly biocompatible and exhibited efficient theranostic properties for inhibiting cancer metastasis, making them promising candidates for clinical translation.

Quality by design endorsed fabrication of Ibrutinib-loaded human serum albumin nanoparticles for the management of leukemia

Ibrutinib (IB), a BCS class II drug suffers from limited aqueous solubility, short half-life and extensive first-pass metabolism. In this project, we aim to recruit the desirable properties of human serum albumin (HSA) as a biocompatible drug carrier to circumvent nanoparticle-associated drawbacks. Quality by design and multivariate analysis was used for the optimization of IB-NPs. Cell culture studies performed on the K562 cell line revealed that the Ibrutinib-loaded HSA NPs demonstrated improved cytotoxicity, drug uptake, and reactive oxygen species generation in the leukemic K562 cells. Cell cycle analysis revealed G2/M phase retention of the leukemia cells. In vitro protein corona and hemolysis studies revealed superior hematological stability compared to the free drug which showed greater than 40 % hemolysis. In vitro drug release studies showed prolonged release profile till 48 h. Pharmacokinetic studies demonstrated a 2.31-fold increase in AUC and an increase in half-life from 0.43 h to 2.887 h with a tremendous reduction in clearance and elimination rate indicating prolonged systemic circulation which is desirable in leukemia. Hence, we conclude that IB-loaded albumin nanoparticles could be a promising approach for the management of leukemia.

A “bulldozer” driven by anoxic bacteria for pancreatic cancer chemo-immunotherapy

Immune evasion is a major obstacle for pancreatic ductal adenocarcinoma (PDAC) therapy. Inhibition of autophagy can improve antigen presentation and enlarge immunogenic cell death (ICD) effect to generate a strong anti-tumor immune response. However, abundant extracellular matrix dominated by hyaluronic acid (HA) hinders the deep penetration of autophagy inhibitors and ICD inducers. Herein, an intelligent autophagy inhibitor hydroxychloroquine (HCQ) and chemotherapeutic drug doxorubicin (DOX) co-loaded “bulldozer” (HD@HH/EcN) driven by anoxic bacteria was constructed for PDAC chemo-immunotherapy. Results demonstrated that probiotic Escherichia coli 1917 (EcN) could carry hyaluronidases (HAases)-hybrided albumin nanoparticles (HD@HH) to reach PDAC tumor tissue quickly and accurately. Thereafter, HAases can efficiently cleave the tumor matrix barrier and promote HD@HH/EcN to accumulate at tumor hypoxic core significantly. After that, high level of glutathione (GSH) in tumor microenvironment (TME) induces intermolecular disulfide bond in HD@HH nanoparticles breakage, to precisely release HCQ and DOX. DOX can induce ICD effect. Meanwhile, HCQ can amplify DOX induced ICD effect by inhibiting tumor autophagy, which further increase cell surface expression of major histocompatibility complex class I (MHC-I) and augment recruitment of CD8+ T cell to improve immunosuppressive TME. This study provides a new strategy for PDAC chemo-immunotherapy.

Dopamine-Conjugated Bovine Serum Albumin Nanoparticles Containing pH-Responsive Catechol-V(III) Coordination for In Vitro and In Vivo Drug Delivery.

V(III) instead of commonly used Fe(III) provided a rich tris-catechol-metal coordination at pH 7.4, which is important for slow drug release at physiological pH. Bovine serum albumin (BSA) functionalized with catechol-containing dopamine (D) and cross-linked using tris-catechol-V(III) coordination yielded pH-responsive compact D-BSA NPs (253 nm). However, conversion to bis- and/or mono-catechol-V(III) complexes in an acidic medium resulted in degradation of NPs and rapid release of doxorubicin (DOX). It was shown that D-BSA NPs entered cancerous MCF-7 cells (66%) more efficiently than non-cancerous HEK293T (33%) in 3 h. Also, DOX-loaded NPs reduced cell viability of MCF-7 by 75% and induced apoptosis in a majority of cells after 24 h. Biodegradability and lack of hemolytic activity were shown in vitro, whereas a lack of toxicity was shown in histological sections of zebrafish. Furthermore, 30% of circulating tumor cells in vasculature in 24 h were killed by DOX-loaded NPs shown with the zebrafish CTC xenograft model.

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.

Anti-Pan-Rspo Chimeric Protein-Conjugated Albumin Nanoparticle Provides Promising Opportunities in Cancer Targeted Therapy.

Rspos (R-spondins) belong to a family of secreted proteins that causes various cancers via interacting the corresponding receptors. However, targeted therapeutic approaches against Rspos are largely lacking. In this study, a chimeric protein Rspo-targeting anticancer chimeric protein (RTAC) is originally designed, engineered, and characterized. RTAC shows satisfactory anticancer effects through inhibition of pan-Rspo-mediated Wnt/β-catenin signaling activation both in vitro and in vivo. Furthermore, a conceptually novel antitumor strategy distinct from traditional drug delivery systems that release drugs inside tumor cells is proposed. A special "firewall" nano-system is designed to enrich on tumor cell surface and cover the plasma membrane, rather than undergoing endocytosis, to block oncogenic Rspos from binding to receptors. Cyclic RGD (Arg-Gly-Asp) peptide-linked globular cluster serum albumin nanoparticles (SANP) are integrated as a vehicle for conjugating RTAC (SANP-RTAC/RGD) for tumor tissue targeting. These nanoparticles can adhere to the tumor cell surface and enable RTAC to locally capture free Rspos with high spatial efficiency and selectivity to antagonize cancer progression. Therefore, this approach offers a new nanomedical anticancer route and obtains the "dual-targeting" capability for effective tumor clearance and low potential toxicity. This study presents a proof-of-concept for anti-pan-Rspo therapy and a nanoparticle-integrated paradigm for targeted cancer treatment.

EGFR targeted albumin nanoparticles of oleanolic acid: In silico screening of nanocarrier, cytotoxicity and pharmacokinetics for lung cancer therapy

This study aimed to develop cetuximab (CTX) functionalized albumin nanoparticles (ALB-NPs) of oleanolic acid for EGFR targeted lung cancer therapy. The molecular docking methodology has been applied for a selection of suitable nanocarrier. Various physicochemical parameters like particle size, polydispersity, zeta potential, morphology, entrapment efficiency, and in-vitro drug release of all the ALB-NPs were analyzed. Furthermore, the in-vitro qualitative and quantitative cellular uptake study revealed that higher uptake of CTX conjugated ALB-NPs than nontargeted ALB-NPs in A549 cells. The in-vitro MTT assay revealed that the IC50 value of CTX-OLA-ALB-NPs (4.34 ± 1.90 μg/mL) was significantly reduced (p < 0.001) than OLA-ALB-NPs (13.87 ± 1.28 μg/mL) in A-549 cells. CTX-OLA-ALB-NPs caused apoptosis in A-549 cells at concentrations equivalent to its IC50 value and blocked the cell cycle in the G0/G1 phases. The hemocompatibility, histopathology and lung safety study confirmed the biocompatibility of the developed NPs. In vivo ultrasound and photoacoustic imaging confirmed the targeted delivery of the NPs to lung cancer. The findings demonstrated that CTX-OLA-ALB-NPs have potential for site-specific delivery of OLA for effective and targeted therapy of lung carcinoma.

Heterologous Prime-boost Vaccination Using Adenovirus and Albumin Nanoparticles as Carriers for Human Papillomavirus 16 E7 Epitope.

Nanocarriers are these days considered an attractive approach in cancer immunotherapy owing to their ability to deliver antigens to antigen-presenting cells (APCs) for stimulating robust immune cells against the tumor. The objective of this study was to construct nanocomplexes using two nanocarriers with negative surface charge, adenovirus (Ad) and human serum albumin nanoparticle (HSA-NP), and coat their surface with a modified and positively-charged HPV16 E7 MHC-I specific epitope to assess their anti-tumor effects in a TC-1 mouse model. After the construction of Ad and HSA-NP, their complexes with HPV16 E7 MHC-I specific epitope were characterized by zeta potential and dynamic light scattering. Then, the cellular immunity and CTL responses in immunized mice were assessed by measuring the levels of IL-10 and IFN-γ and the expression of CD107a, a marker of CTL response, as well as tumor inhibition. The zeta potential and dynamic light scattering results showed that incubation of the oppositely- charged nanocarriers and MHC-I specific epitope led to the formation of nanocomplexes in which the surface charge of nanocarriers was changed from negative to positive with minimal changes in the particle size. We demonstrated that the nanocomplex platforms in heterologous primeboost regimens generate significantly higher E7-specific IL-10, IFN-γ, and CTL responses. Moreover, the heterologous nanocomplex regimens, Alb/Pep-Ad/Pep and Ad/Pep-Alb/Pep, significantly suppressed the growth of TC-1 tumors in vivo compared with mice receiving homologous regimens and naked nanocarriers. The heterologous nanocomplexes might serve as an effective vaccine strategy against HPV-induced cervical cancer.

A fibroblastic foci-targeting and hypoxia-cleavable delivery system of pirfenidone for the treatment of idiopathic pulmonary fibrosis

The progressive formation of fibroblastic foci characterizes idiopathic pulmonary fibrosis (IPF), and excessive oral doses of approved pirfenidone (PFD) always cause gastrointestinal side effects. The fibrotic response driven by activated fibroblasts could perpetuate epithelial damage and promote abnormal extracellular matrix (ECM) deposition. When modified nanoparticles reach their target, it is important to ensure a responsive release of PFD. Hypoxia is a determining factor in IPF, leading to alveolar dysfunction and deeper cellular fibrosis. Herein, a fibroblastic foci-targeting and hypoxia-cleavable drug delivery system (Fn-Azo-BSA@PEG) was established to reprogram the fibrosis in IPF. We have modified the FnBAP5 peptide to enable comprehensive fibroblastic foci targeting, which helps BSA nanoparticles recognize and accumulate at fibrotic sites. Meantime, the hypoxia-responsive azobenzene group allowed for efficient and rapid drug diffusion, while the PEGylated BSA reduced system toxicity and increased circulation in vivo. As expected, the strategy of the fibronectin-targeting-modification and hypoxia-responsive drug release synergistically inhibited activated fibroblasts and reduced the secretion of the fibrosis-related protein. Fn-Azo-BSA@PEG could accumulate in pulmonary tissue and prolong the survival time in bleomycin-induced pulmonary fibrosis mice. Together, the multivalent BSA nanoparticles offered an efficient approach for improving lung architecture and function by regulating the fibroblastic foci and hypoxia. Statement of significanceWe established fibroblastic foci-targeting and hypoxia-cleavable bovine serum albumin (BSA) nanoparticles (Fn-Azo-BSA@PEG) to reprogramme the fibroblastic foci in idiopathic pulmonary fibrosis (IPF). Fn-Azo-BSA@PEG was designed to actively target fibroblasts and abnormal ECM with the FnBPA5 peptide, delivering more FDA-approved pirfenidone (PFD) to the cross-talk within the foci. Once the drug reached fibroblastic foci, the azobenzene group acted as a hypoxia-responsive linker to trigger effective and rapid drug release. Hypoxic responsiveness and FnBAP5-modification of Fn-Azo-BSA@PEG synergistically inhibited the secretion of proteins closely related to fibrogenesis. BSA's inherent transport and metabolic pathways in the pulmonary reduced the side effects of the main organs. The multivalent BSA nanoparticles efficiently inhibited IPF-fibrosis progress and preserved the lung architecture by regulating the fibroblastic foci and hypoxia.

The Role of Selenium Nanoparticles in the Treatment of Liver Pathologies of Various Natures.

The liver is the body's largest gland, and regulates a wide variety of physiological processes. The work of the liver can be disrupted in a variety of pathologies, the number of which is several hundred. It is extremely important to monitor the health of the liver and develop approaches to combat liver diseases. In recent decades, nanomedicine has become increasingly popular in the treatment of various liver pathologies, in which nanosized biomaterials, which are inorganic, polymeric, liposomal, albumin, and other nanoparticles, play an important role. Given the need to develop environmentally safe, inexpensive, simple, and high-performance biomedical agents for theragnostic purposes and showing few side effects, special attention is being paid to nanoparticles based on the important trace element selenium (Se). It is known that the metabolism of the microelement Se occurs in the liver, and its deficiency leads to the development of several serious diseases in this organ. In addition, the liver is the depot for most selenoproteins, which can reduce oxidative stress, inhibit tumor growth, and prevent other liver damage. This review is devoted to the description of the results of recent years, revealing the important role of selenium nanoparticles in the therapy and diagnosis of several liver pathologies, depending on the dose and physicochemical properties. The possibilities of selenium nanoparticles in the treatment of liver diseases, disclosed in the review, will not only reveal the advantages of their hepatoprotective properties but also significantly supplement the data on the role of the trace element selenium in the regulation of these diseases.

Human Serum Albumin Nanoparticles: Synthesis, Optimization and Immobilization with Antituberculosis Drugs.

The aim of this study was to create nanoparticles of human serum albumin immobilized with anti-TB drugs (rifampicin, isoniazid) using the desolvation method. Central Composite Design (CCD) was applied to study the effect of albumin, urea, L-cysteine, rifampicin and isoniazid concentration on particle size, polydispersity and loading degree of the drugs. The optimized nanoparticles were spherical in shape with an average particle size of 216.7 ± 3.7 nm and polydispersity of 0.286 ± 4.9. The loading degree of rifampicin and isoniazid in the optimized nanoparticles were 44% and 27%, respectively. The obtained nanoparticles were examined by Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC); the results showed the absence of drug-polymer interactions. The drug release from the polymer matrix was studied using dialysis membranes.

Quetiapine Albumin Nanoparticles as an Efficacious Platform for Brain Deposition and Potentially Improved Antipsychotic Activity.

Quetiapine (QP) is a second-generation short-acting antipsychotic drug extensively metabolized in the liver, producing pharmacologically inactive metabolites and leading to diminished bioavailability. Therefore, this study aimed to develop an intravenous QP albumin nanoparticles (NPs) system for improving QP antipsychotic activity and brain targeting. QP-loaded albumin NPs were prepared by the desolvation method. The fabricated NPs were characterized in terms of particle size, zeta potential, entrapment efficiency (EE%), and in vitro drug release. In vivo pharmacokinetics and biodistribution in rats were studied. In addition, the antipsychotic activity of the optimized platform was also investigated. Human serum albumin (HSA) concentration, pH, and stirring time were modulated to optimize QP albumin NPs with a particle size of 103.54 ± 2.36 nm and a QP EE% of 96.32 ± 3.98%. In addition, the intravenous administration of QP albumin NPs facilitated QP brain targeting with a 4.9-fold increase in targeting efficiency compared to the oral QP solution. The QP albumin NPs improved the QP antipsychotic activity, indicated by suppressing rats' hypermobility and reducing the QP's extrapyramidal side effects. The obtained results proposed that intravenous QP- NPs could improve QP brain targeting and its antipsychotic efficiency.

Proteolytic Resistance Determines Albumin Nanoparticle Drug Delivery Properties and Increases Cathepsin B, D, and G Expression.

Proteolytic activity is pivotal in maintaining cell homeostasis and function. In pathological conditions such as cancer, it covers a key role in tumor cell viability, spreading to distant organs, and response to the treatment. Endosomes represent one of the major sites of cellular proteolytic activity and very often represent the final destination of internalized nanoformulations. However, little information about nanoparticle impact on the biology of these organelles is available even though they represent the major location of drug release. In this work, we generated albumin nanoparticles with a different resistance to proteolysis by finely tuning the amount of cross-linker used to stabilize the carriers. After careful characterization of the particles and measurement of their degradation in proteolytic conditions, we determined a relationship between their sensitivity to proteases and their drug delivery properties. These phenomena were characterized by an overall increase in the expression of cathepsin proteases regardless of the different sensitivity of the particles to proteolytic degradation.

Elucidating the binding mechanism between bovine serum albumin and TiO2 nanoparticles with diverse properties: Insights from spectroscopic methods and molecular docking simulation

The interaction mechanism between bovine serum albumin (BSA) and titanium dioxide (TiO2) nanoparticles with different shapes, surface charge and hydrophobic properties was studied using multiple spectral methods and molecular docking simulation. UV–vis spectra showed that when BSA interacted with the four TiO2 NPs, the TiO2 nanoparticles and BSA formed a stable ground state complex. Fluorescence spectra showed that the binding capacities of four different types of TiO2 nanoparticles with BSA are as follows: spherical TiO2 (s-TiO2) > rod-shaped TiO2 (r-TiO2) > positively charged TiO2 (c-TiO2) > hydrophobic TiO2 (h-TiO2). The results of synchronous fluorescence, circular dichroism (CD) and Fourier transform infrared (FTIR) spectroscopy revealed that s-TiO2, r-TiO2, and c-TiO2 have a weak effect on the conformation of BSA, whereas h-TiO2 has a greater effect. Molecular docking and MD simulations results show that the content of hydroxyl groups plays a key role in the binding capacity.

Customizable resveratrol spray-dried micro-composites for inhalation as a promising contender for treatment of idiopathic pulmonary fibrosis

The past decades have witnessed tremendous expansion in utilization of plant-derived medicines as resveratrol (RES) in treating several diseases like idiopathic pulmonary fibrosis (IPF). RES can exhibit its role in treating IPF via its outstanding antioxidant and anti-inflammatory activities. The goal of this work was to formulate RES-loaded spray-dried composite microparticles (SDCMs) suitable for pulmonary delivery via dry powder inhaler (DPI). They were prepared by spray drying of a previously prepared RES-loaded bovine serum albumin nanoparticles (BSA NPs) dispersion using different carriers. RES-loaded BSA NPs, prepared by the desolvation technique, acquired suitable particle size of 177.67 ± 0.95 nm and entrapment efficiency of 98.7 ± 0.35% with perfectly uniform size distribution and high stability. Considering the attributes of the pulmonary route, NPs were co-spray dried with compatible carriers viz. mannitol, dextran, trehalose, leucine, glycine, aspartic acid, and glutamic acid to fabricate SDCMs. All formulations showed suitable mass median aerodynamic diameter<5 µm; that is suitable for deep lung deposition. However, the best aerosolization behavior was attained from using leucine with fine particle fraction (FPF) of 75.74%, followed by glycine with FPF of 54.7%. Finally, a pharmacodynamic study was conducted on bleomycin-induced mice, and it strongly revealed the role of the optimized formulations in alleviating PF through suppressing the levels of hydroxyproline, tumor necrosis factor-α and matrix metalloproteinase-9 with obvious improvements in the treated lung histopathology. These findings indicate that in addition to leucine, the glycine amino acid, which is not commonly used yet, is very promising in the formulation of DPIs.

Rheological, Physical, and Spectroscopical Characterization of Gamma-Irradiated Albumin Nanoparticles Loaded with Anthocyanin.

Anthocyanins are the main active compounds in blueberry. However, they have poor oxidation stability. If anthocyanins are encapsulated in protein nanoparticles, their oxidation resistance could be increased as a result of the slowing down of the oxidation process. This work describes the advantages of using a γ-irradiated bovine serum albumin nanoparticle bound to anthocyanins. The interaction was characterized biophysically, mainly by rheology. By computational calculation and simulation based on model nanoparticles, we estimated the number of molecules forming the albumin nanoparticles, which allowed us to infer the ratio of anthocyanin/nanoparticles. Measurements by UV-vis spectroscopy, FTIR spectroscopy, fluorescence spectroscopy, dynamic light scattering (DLS), ζ potential, electron transmission microscopy, and rheology at room (25 °C) and physiological (37 °C) temperatures were performed. The spectroscopy measurements allowed identifying additional hydrophobic sites created during the irradiation process of the nanoparticle. On the basis of the rheological studies, it was observed that the BSA-NP trend is a Newtonian flow behavior type for all the temperatures selected, and there is a direct correlation between dynamic viscosity and temperature values. Furthermore, when anthocyanins are added, the system increases its resistance to the flow as reflected in the morphological changes observed by TEM, thus confirming the relationship between viscosity values and aggregate formation.

The interplay of solvent-drug-protein interactions during albumin nanoparticles formulations for temozolomide delivery to brain cancer cells.

Temozolomide (TMZ), the first line for glioma therapy, suffers from stability at physiological pH. TMZ was selected as a challenging model drug for loading into human serum albumin nanoparticles (HSA NPs). Our aim is to optimise the conditions for TMZ loading into HSA NPs while ensuring TMZ stability. Blank and TMZ-HSA NPs were fabricated using the de-solvation technique and the effect of different formulation parameters was evaluated. For blank NPs, crosslinking time had no significant effect on NPs' size while acetone produced significantly smaller particles than ethanol. Upon drug loading, though TMZ was stable in acetone and ethanol as single agents yet, ethanol-based NPs showed misleadingly high EE% due to drug instability in ethanol formulations as evident by the UV spectrum.The optimum conditions for drug-loaded particles were: 10 mg/ml HSA, 4 mg TMZ using acetone, yielded NPs with 145 nm in diameter, ξ of -16.98 mV and 0.16% DL. The selected formula reduced the cell viabilities of GL261 glioblastoma cells and BL6 glioblastoma stem cells to 61.9% and 38.3%, respectively. Our results corroborated that careful manipulation of TMZ formulation processing parameters is crucial for encapsulating such chemically unstable dug while simultaneously ensuring its chemical stability.

Tailoring albumin-based theranostic PROTACs nanoparticles for enhanced NIR-II bioimaging and synergistic cancer chemo-phototherapy

PROteolysis TArgeting Chimeras (PROTACs), a developing therapeutic tool designed to dictate target proteins for proteolysis through hijacking the ubiquitin–proteasome system, show potential for cancer therapy. However, unfavorable solubility and poor permeability of traditional PROTACs lead to low bioavailability and insufficient tumor distribution, which limit their clinical applications. Herein, we report a tridentate molecular probe (PROTAC-Cy7) by a three-in-one molecular designing strategy, which integrated a warhead that binds to MCL-1, the E3 ligase ligand pomalidomide and a heptamethine cyanine linker connecting the warhead and the ligand into the same scaffold. Then, bovine serum albumin (BSA) nanoparticles (NPs) with excellent biocompatibility, nonantigenic and biosafety were utilized to manufacture water-insoluble PROTAC-Cy7. The prepared PROTAC-Cy7@BSA NPs demonstrated tumor targeting and efficient degradation of MCL-1 through specific binding to MCL-1 receptors, which are overexpressed in multiple tumors. Moreover, PROTAC-Cy7@BSA NPs can be successfully used for near-infrared-II (NIR-II) noninvasively biomedical vascular imaging and to perform tumor resection guided by intraoperative real-time imaging. Under 808 nm laser irradiation, PROTAC-Cy7@BSA NPs exhibited synergistic Chemo-Phototherapy and showed perfect tumor suppression with 100% survival rate throughout the course of 60-day monitoring period. Our work provides a simple and feasible strategy for designing multifunctional drugs to have imaging-guided tumor-targeted multimodal therapy.

Mechanism of miR-125b-5p Carried with Albumin Nanoparticles in Protecting the Injured Nerve Cells in Ischemia-Reperfusion Cerebral Injury

This study assessed the mechanism of miR-125b-5p carried with albumin nanoparticles on injured nerve cells in ischemia-reperfusion cerebral injury. 50 rats were assigned into control set, model set, miR-125b-5p set, IL-6/STAT3 agonist set, and positive control set. The score of neurological impairment, cerebral infarction volume, cerebral water content, apoptosis index of brain cells, synaptic ultrastructure, miR-125b-5p expression, level of IL-6/STAT3 pathway factors, targeting correlation between miR-125b-5p and IL-6 were observed. There was a good dispersibility and uniform size in albumin nanoparticles with an average particle size of 15.5 nanometer. The neurological impairment, cerebral infarction volume, cerebral water content, apoptosis index of brain cells in model set and IL-6/STAT3 agonist set were the highest followed by miR-125b-5p set and positive control set. The level of inflammatory reaction in model set and IL-6/STAT3 agonist set were the highest and oxidative stress were the lowest. miR-125b-5p carried with albumin nanoparticles could directly target on IL-6. The phosphorylation level of IL-6 and STAT3 could be restrained. The activity of IL-6/STAT3 signal pathway could be inhibited, leading to restrained inflammation and oxidative stress in nervous system and reduced cerebral water content, therefore protecting nerve cells. The mechanism might be related with restrained IL-6/STAT3 pathway.

Sustained release of resveratrol from fused deposition modelling guided 3D porous scaffold for bone tissue engineering

To promote bone regeneration, bone tissue engineering necessitates development of a three-dimensional porous scaffold with osteoconductive, osteoinductive, and osteogenic features. In this study, a milliporous polylactic acid (PLA) scaffold was 3D printed, into which a microporous polycaprolactone scaffold releasing resveratrol was embedded. Herein, resveratrol-loaded albumin nanoparticles (RSV-Np) were synthesized, homogenously mixed with polycaprolactone (10% w/v & 12% w/v) at 2 different concentrations, and subsequently embedded into the milliporous PLA scaffold. Further, morphological analysis by field emission scanning electron microscopic (FESEM) analysis demonstrated interconnected pores measuring 100–300 µm diameter, and homogenous embedment of RSV-Np throughout the surface. In addition, XRD analysis inferred that resveratrol was present in an amorphous phase in the scaffold, which improves dissolution of the drug, thereby advantageous for drug delivery applications. Furthermore, successful incorporation of RSV-Np was validated by Raman spectroscopy and Fourier transform infrared spectroscopy. The drug release study implied that RSV-Np concentration modulated the resveratrol release from scaffolds. Moreover, in vitro testing of the scaffolds for 16 days showed that resveratrol sustained release enhanced the osteogenic potential of scaffolds. In summary, such scaffolds can be a potential matrix for bone regeneration due to their inherent ability to release resveratrol in a controlled fashion.