Search

The clinical advancement of protein-based nanomedicine has revolutionized medical professionals' perspectives on cancer therapy. Protein-based nanoparticles have been exploited as attractive vehicles for cancer nanomedicine due to their unique properties derived from naturally biomacromolecules with superior biocompatibility and pharmaceutical features. Furthermore, the successful translation of Abraxane™ (paclitaxel-based albumin nanoparticles) into clinical application opened a new avenue for protein-based cancer nanomedicine. In this mini-review article, we demonstrate the rational design and recent progress of protein-based nanoparticles along with their applications in cancer diagnosis and therapy from recent literature. The current challenges and hurdles that hinder clinical application of protein-based nanoparticles are highlighted. Finally, future perspectives for translating protein-based nanoparticles into clinic are identified.

Biomimetic nanoparticles represent a promising avenue for mitigating rapid clearance by the reticuloendothelial system (RES); however, current challenges include insufficient tumour targeting, suboptimal adhesion, and inadequate localized drug release within tumour regions. These shortcomings contribute to persistent contests, such as recurrence and pulmonary metastasis, even with advanced breast cancer therapies. Stimuli-sensitive drug release can furbish the membrane coated nanoparticles for their efficiency against the stated problems. To enhance the efficacy of biomimetic nanoparticles in addressing these issues, we proposed a versatile, stimuli-responsive drug delivery system by encapsulating doxorubicin (Dox) and perfluorohexane (PFH) within poly (lactic-co-glycolic acid) (PLGA) nanoparticles, subsequently coated with macrophage-derived cell membranes. Within this framework, PFH serves as the mediator for ultrasonic (US)-irradiation-triggered drug release specifically within tumour microenvironment, while the macrophage-derived cell membrane coating enhances cell adhesion, enables immune evasion, and natural tumour-homing ability. The characterization assays and in vitro evaluations yielded encouraging results, indicating enhanced targeting and release efficiencies. In vivo studies demonstrated marked inhibitory effects on both breast cancer recurrence and pulmonary metastasis. The resulting data indicate that these engineered nanoparticles have notable potential for targeted delivery and controlled release upon US irradiation, thereby offering significant therapeutic efficacy against primary breast cancer, pulmonary metastasis, and recurrent malignancies. Our findings lay the groundwork for a novel clinical approach, representing an intriguing direction for ongoing investigation by oncologists.

Abstract Treatment of castration‐resistant prostate cancer (CRPC) is a long‐standing clinical challenge. Traditionally, CRPC drugs work by either reducing dihydrotestosterone biosynthesis or blocking androgen receptor (AR) signaling. Here it is demonstrated that AR inhibitor treatment gives rise to a drug‐tolerant persister (DTP) state. The thioredoxin/peroxiredoxin pathway is up‐regulated in DTP cells. Peroxiredoxin 5 (PRDX5) promotes AR inhibitor resistance and CRPC development. Inhibition of PRDX5 suppresses DTP cell proliferation in culture, dampens CRPC development in animal models, and stabilizes PSA progression and metastatic lesions in patients. Therefore, the study provides a novel mechanism and potential target for the management of castration‐resistant prostate cancer.

Abstract The study aimed to investigate the mechanism of action of β-elemene (ELE) in the treatment of esophageal cancer (EC). In this study, public databases were used to predict related targets in ELE and EC. The network analysis was performed to identify key targets of ELE in EC treatment. Further, bioinformatics and DAVID databases were used for GO and KEGG enrichment analysis, respectively. Ultimately, molecular docking and in vitro cell experiments were conducted to validate the results of network pharmacology enrichment. As a result, 34 candidate targets for ELE in the treatment of EC were obtained, and five key targets (STAT3, EGFR, CTNNB1, BCL2L1 and CASP9) were identified. GO functional annotation yielded 2200 GO entries (p

Itraconazole (ITZ) is a renowned antifungal medication, however its therapeutic efficacy is limited by low solubility and oral bioavailability. The current research work attempted to augment the oral bioavailability of ITZ by incorporating into self-emulsifying micelles (SEMCs). To fabricate the SEMCs, various preparation techniques including physical mixture, melt-emulsification, solvent evaporation and kneading, were opted by using different weight ratio of drug and solubilizers i.e. Gelucire-50/13 or Gelucire-44/14 and characterized both in vitro and in vivo. The prepared SEMCs were found to be in the size range from 63.4 ± 5.2 to 284.2 ± 19.5 nm with surface charges ranging from −16 ± 1.2 to −27 ± 2.0 mV. The drug solubility was improved to a reasonable extent with all investigated formulations, however, SEMCs in group 6 prepared by kneading method (KMG6) using Gelucire-44/14: drug (10:1 presented 87.6 folds’ increase (964.93 ± 2 μg/mL) compared to solubility of crystalline ITZ (11 ± 2 μg/mL) through kneading method. In addition, KMG6 SEMCs shows the fast drug release compared to other SEMCs. Further, KMG6 SEMCs also exhibited 5.12-fold higher relative intestinal serosal fluid absorption compared to crystalline ITZ. The pharmacokinetic parameters such Cmax, AUC and Tmax of KMG6 SEMCs significantly improved compared to crystalline ITZ. In conclusion, the manipulation of ITZ solubility, dissolution rate and absorption using SEMCs is a promising strategy for bioavailability enhancement.

Mixing different kind inhalation medications for simultaneous inhalation is widely used in the treatment of chronic respiratory diseases, and it can minimize the administration time and improve patient adherence. To our knowledge, it is unclear whether beclomethasone (BDP, Clenil®) can bemixed with acetylcysteine (NAC, Fluimucil®), because the in vitro physico-chemical compatibility and aerosol characteristics of the mixture are unknown. In this study, we investigated physical compatibility, including the appearance, pH, osmotic pressure and chemical stability, as well as aerosol characteristics, including particle size corresponding to 10%/50%/90% of the cumulative percentage of total particle volume (X10/X50/X90), volume median droplet diameter (VMD), mass median aerodynamic diameter (MMAD), fine particle fraction (FPF), fine particle dose (FPD) and geometric standard deviation (GSD), delivery rate, and total delivery of the above solutions. After mixing, there were no significant changes in visual appearance, pH, osmolality and drug content of the mixtures at room temperature for 12 h. The FDP of BDP in the mixture decreased by 16.49%, whereas the NAC increased by 10.85%. The delivery rates of BDP and NAC in the mixture decreased by 66.05% and 45.54%, and total delivery increased by 13.20% and 25.29%, respectively. However, the MMAD, FPF, particle size and GSD of the mixture were almost unchanged. We demonstrated that these admixtures are physico-chemically compatible but that coadministration of beclomethasone with acetylcysteine can markedly affect output and aerosol characteristics.

Background: Sodium-glucose cotransport protein 2 (SGLT2) inhibitors, a new type of glucose-lowering drug, have been well proved in several clinical studies for their glucose-lowering and nephroprotective effects, and the nephroprotective effects include both indirect effects of metabolic improvement and direct effects, independent of glucose-lowering effects. Summary: In patients with diabetic kidney disease (DKD), several studies have demonstrated the potential nephroprotective mechanisms of SGLT2 inhibitors, and evidence of nephroprotective mechanisms in the non-DKD population is accumulating. Although the nephroprotective mechanism of SGLT2 inhibitors has not been fully elucidated, several laboratory studies have illustrated the mechanism underlying the effects of SGLT2 inhibitors at various aspects. Key Messages: The purpose of this article is to review the mechanism of nephroprotective effect of SGLT2 inhibitors and to look forward to promising research in the future.

The peel from Citrus-sinensis L. is a medicinally significant food waste, and its extract (O-Ext) could be significant against oxidative stresses and skin aging, However, the penetration barriers, instability in formulation, undefined toxicities, and enzymatic activities make the O-Ext difficult to formulate and commercialize. The goal of this study was to evaluate O-Ext against oxidative stress, prepare O-Ext-loaded nano-lipid carriers (O-NLCs), and load them into topical O/W-emulsion (O-NLC-E) to improve O-Ext permeation and its in vivo antiaging effects. TPC, TFC, DPPH activity, and mineral/metal contents of O-Ext were determined via atomic-absorption spectroscopy. For bioactive compounds profiling, GC-MS analysis was carried out. O-NLCs were prepared and tested for physicochemical attributes, while HaCaT and fibroblast cells were used to study permeation and cytotoxicity. The kinetic characteristics of ex vivo permeation through rat skin were established, following the Higuchi model. Following written consent, safety investigations were conducted on human volunteers for three months, where optimized O-NLC-E and B-NLC-E were regularly applied on cheeks. Non-invasive procedures were used to assess the volunteer’s skin erythema, TEWL, sebum level, melanin, hydration, pH, elasticity, and pore sizes after specified intervals. The results demonstrated that applying O-NLC-E formulation to the skin of volunteers directed significant antiaging benefits. The study offers nanotechnology-based sustainability approach against skin ageing.

Abstract Genetic polymorphisms in the MTNR1B gene is associated with type 2 diabetes mellitus (T2DM); however, there is no evidence about its impact on the therapeutic efficacy of nateglinide. This prospective case–control study was designed to investigate the effect of MTNR1B rs10830963 gene variant on the therapeutic efficacy of nateglinide in treating T2DM. We genotyped untreated T2DM patients (N = 200) and healthy controls (N = 200) using the method of the high resolution of melting curve (HRM). Newly diagnosed T2DM patients (n = 60) with CYP2C9*1 and SLCO1B1 521TT genotypes were enrolled and given oral nateglinide (360 mg/d) for 8 weeks. The outcome was measured by collecting the venous blood samples before and at the 8th week of the treatment. The risk G allelic frequency of MTNR1B rs10830963 was higher in T2DM patients than the healthy subjects (P

Breast cancer brain metastases (BCBMs) are one of the most difficult malignancies to treat due to the intracranial location and multifocal growth. Chemotherapy and molecular targeted therapy are extremely ineffective for BCBMs due to the inept brain accumulation because of the formidable blood‒brain barrier (BBB). Accumulation studies prove that low density lipoprotein receptor-related protein 1 (LRP1) is promising target for BBB transcytosis. However, as the primary clearance receptor for amyloid beta and tissue plasminogen activator, LRP1 at abluminal side of BBB can clear LRP1-targeting therapeutics. Matrix metalloproteinase-1 (MMP1) is highly enriched in metastatic niche to promote growth of BCBMs. Herein, it is reported that nanoparticles (NPs-K-s-A) tethered with MMP1-sensitive fusion peptide containing HER2-targeting K and LRP1-targeting angiopep-2 (A), can surmount the BBB and escape LRP1-mediated clearance in metastatic niche. NPs-K-s-A revealed infinitely superior brain accumulation to angiopep-2-decorated NPs-A in BCBMs bearing mice, while comparable brain accumulation in normal mice. The delivered doxorubicin and lapatinib synergistically inhibit BCBMs growth and prolongs survival of mice bearing BCBMs. Due to the efficient BBB penetration, special and remarkable clearance escape, and facilitated therapeutic outcome, the fusion peptide-based drug delivery strategy may serve as a potential approach for clinical management of BCBMs.

Purpose: We aimed to find critical biomakers associated with BRCA1-mutation positive breast cancer.

Although Mangifera indica L. extract (M-Ext) of the peel and kernel possesses potent antioxidant and excellent antiaging qualities, the effects are only partially seen because of the skin’s limited ability to absorb it. M-Ext was loaded into nanolipid carriers (M-NLCs) in this work to create a green topical formulation that would boost antiaging efficacy and address penetration deficit. Compound identification was done using GCMS and atomic absorption spectroscopy for heavy metals in M-Ext. M-Ext was also evaluated against oxidative stress antioxidant enzymes. The M-NLCs were fabricated and evaluated for their physicochemical characterizations. Cytotoxicity and cell permeation analysis of M-Ext and M-NLCs were carried out in fibroblasts and HaCaT cell lines. An ex vivo permeation study of M-Ext and M-NLC-loaded emulsion was performed through rat skin and the kinetic parameters were determined. Kinetic data showed that the ex vivo permeation of M-NLC-loaded emulsion through rat skin followed the Higuchi model. The safety profile was evaluated in human volunteers after written consent. Three months’ in vivo investigations were conducted using the optimized M-NLC-loaded emulsion and vehicle (B-NLC-loaded emulsion) on human cheeks for comparison. The volunteers’ skin erythema level, melanin contents, TEWL index, moisture contents, sebum level, elasticity, pH, and pore size were examined after the first, second, and third month via noninvasive techniques. There were significant findings for physicochemical characterizations and in vitro and ex vivo studies. The findings demonstrate that the green nanolipid carriers amplified the overall antioxidant effectiveness and may represent an emerging treatment strategy for oxidative stresses and aging.

Recently, biomimetic nanoparticles for tumor−targeted therapy have attracted intensifying interest. Although exosomes are an excellent biomimetic material, numerous challenges are still hindering its clinical applications, such as low yield, insufficient targeting efficiency, and high cost. In this work, urinary exosomes (UEs) with high expression of CD9 and CD47 were extracted from breast cancer patients by a non−invasive method. Here, a nanotechnology approach is reported for tumor homologous targeting via CD9 and phagocytosis escape via CD47 through UE−coated poly (2−ethyl−2−oxazoline)−poly (D, L−lactide) (PEOz−PLA) nanoparticles (UEPP NPs). The cytotoxic agent doxorubicin (DOX)−loaded UEPP (UEPP−D) NPs with an initial particle size of 61.5 nm showed a burst release under acidic condition mimicking the tumor microenvironment. In vitro experiments revealed that UEPP−D NPs exhibited significantly improved cellular uptake, cytotoxicity, and apoptosis in MCF−7 cell lines as compared to DOX−loaded PEOz−PLA nanoparticles (PP−D NPs) and free DOX. More importantly, anti−phagocytosis and pharmacokinetic studies confirmed that UEPP−D NPs had superior immune escape ability and significantly prolonged the drug’s bloodstream circulation in vivo. Finally, UEPP−D NPs showed a markedly higher antitumor efficacy and lower side−toxicity in MCF−7 tumor bearing nude mice model. Thus, this versatile nano−system with immune escape, homologous targeting, and rapid response release characteristics could be a promising tool for breast cancer treatment.

Cancer vaccine is widely considered as a powerful tool in immunotherapy. In particular, the effective antigen processing and presentation natures of dendritic cell (DC) have made it a promising target for the development of therapeutic vaccine for cancer treatment. Here in our study, a versatile cancer cell membrane (CCM) coated calcium carbonate (CC) nanoparticles (MC) that capable of generating in situ tumor-associated antigens (TAAs) for DC vaccination is developed. Low-dose doxorubicin hydrochloride (Dox) could be encapsulated in the CC core of MC to trigger immunogenic cell death (ICD) while chlorins e6 (Ce6), a commonly adopted photosensitizer, was loaded in the CCM of MC for effective photodynamic therapy (PDT) through the generation of reactive oxygen species (ROS) to finally construct the vaccine (MC/Dox/Ce6). Most importantly, our in-depth study revealed the treatment of MC/Dox/Ce6 was able to elicit TAAs population and DC recruitment, triggering the following immune response cascade. In particular, the recruited DC cells could be stimulated in situ for effective vaccinations. Both in vitro and in vivo experiments suggested the capability of this all-in-one DDS to enhance DCs maturation to finally result in effective inhibition of both primary and distant growth of breast cancer upon single administration of low dose Dox and Ce6.

High impedance faults (HIFs) are easy to occur in collective feeders in wind farms and may cause the cascading of wind generators tripping. This kind of faults is difficult to be detected by traditional relay or fuse due to the limited fault current values and the situation is worse in wind farms. The mostly adopted HIF detection algorithms are based on the 3rd harmonic characteristic of the fault zero-sequence currents, whereas these 3rd harmonics are very easy to be polluted by wind power back-to-back converters. In response to this problem, the typical harmonic characteristic of HIF arc flash based on Mayr's arc model is first analyzed, and the typical fault waveforms of HIF in wind farm are presented. Then the performance of the harmonic based HIF detection algorithm is discussed, and a novel detection algorithm is proposed from the viewpoint of time domain, focusing on the convex and concave characteristic of zero-sequence current at zero-crossing points. A HIFs detection (HIFD) prototype implementing the proposed algorithm has been developed. The sensitivity and security of the algorithm are proved by field data and RTDS experiments.

Polymer‐based afterglow materials with persistent room temperature phosphorescence (pRTP) have attracted ever‐increasing attention due to their excellent mechanical property, suitability for large‐area production, and diverse processing methods. However, most pRTP polymers were solution‐processed into the films via casting. Herein, a simple processing method of melt‐pressing was proposed, which can improve the phosphorescence of various emitters when doped into polyamide‐12 (PA12) or its copolymer PA4 matrix. Notably, for Be@PA4 and Ch@PA4 (benzo[c]phenanthrene, Be and chrysene, Ch), their casted films did not show any afterglow, while the melt‐pressed ones exhibited bright afterglow of over 4.0 s, even if there were no hydrogen or ionic interaction between the emitters and the matrix. Detailed investigations demonstrate the melt‐pressing procedure can increase the non‐covalent interaction among the matrix as well as offer a rigid and dense environment. The melt‐pressed RTP improvement strategy was also applied to other polar polymers. Additionally, the melt‐pressing method would be of great potential in high‐level anti‐counterfeiting like preparing colorful camouflage patterns. Therefore, we offered a feasible method of melt‐pressing to improve the phosphorescence of polymeric materials without a change in chemical composition or feeding ratio. This work also gained a deeper understanding of the luminescence of polymer‐based systems. [ABSTRACT FROM AUTHOR]