Additive nanomanufacturing of lab-on-a-chip fluorescent peptide nanoparticle arrays for Alzheimer＇s disease diagnosis

This paper proposes an additive nanomanufacturing approach to fabricate a personalized lab-on-a-chip fluorescent peptide nanoparticles （f-PNPs） array for simultaneous multi-biomarker detection that can be used in Alzheimer＇s disease （AD） diagnosis. We will discuss optimization techniques for the additive nanomanufacturing process in terms of reliability, yield and manufacturing efficiency. One contribution of this paper lies in utilization of additive nanomanufacturing techniques to fabricate a patient-specific customize-designed lab-on-a-chip device for personalized AD diagnosis, which remains a major challenge for biomedical engineering. Through the integrated bio-design and bio-manufacturing process, doctor＇s check- up and computer-aided customized design are integrated into the lab-on-a-chip array for patient-specific AD diagnosis. In addition, f-PNPs with targeting moieties for personalized AD biomarkers will be self-assembled onto the customized lab-on-a- chip through the additive nanomanufacturing process, which has not been done before. Another contribution of this research is the personalized lab-on-a-chip f-PNPs array for AD diagnosis utilizing limited human blood. Blood-based AD assessment has been described as ＂the holy grail＂ of early AD detection. This research created the computer-aided design, fabrication through additive nanomanufacturing, and validation of the f-PNPs array for AD diagnosis. This is a highly interdisciplinary research contributing to nanotechnology, biomaterials, and biomedical engineering for neurodegenerative disease. The conceptual work is preliminary with intent to introduce novel techniques to the application. Large-scale manufacturing based on the proposed framework requires extensive validation and optimization.

Smart nanoparticles for cancer therapy

Smart nanoparticles,which can respond to biological cues or be guided by them,are emerging as a promising drug delivery platform for precise cancer treatment.The field of oncology,nanotechnology,and biomedicine has witnessed rapid progress,leading to innovative developments in smart nanoparticles for safer and more effective cancer therapy.In this review,we will highlight recent advancements in smart nanoparticles,including polymeric nanoparticles,dendrimers,micelles,liposomes,protein nanoparticles,cell membrane nanoparticles,mesoporous silica nanoparticles,gold nanoparticles,iron oxide nanoparticles,quantum dots,carbon nanotubes,black phosphorus,MOF nanoparticles,and others.We will focus on their classification,structures,synthesis,and intelligent features.These smart nanoparticles possess the ability to respond to various external and internal stimuli,such as enzymes,pH,temperature,optics,and magnetism,making them intelligent systems.Additionally,this review will explore the latest studies on tumor targeting by functionalizing the surfaces of smart nanoparticles with tumor-specific ligands like antibodies,peptides,transferrin,and folic acid.We will also summarize different types of drug delivery options,including small molecules,peptides,proteins,nucleic acids,and even living cells,for their potential use in cancer therapy.While the potential of smart nanoparticles is promising,we will also acknowledge the challenges and clinical prospects associated with their use.Finally,we will propose a blueprint that involves the use of artificial intelligence-powered nanoparticles in cancer treatment applications.By harnessing the potential of smart nanoparticles,this review aims to usher in a new era of precise and personalized cancer therapy,providing patients with individualized treatment options.

Tetrapeptide self-assembled multicolor fluorescent nanoparticles for bioimaging applications

The biocompatibility and biodegradability of peptide self-assembled materials makes them suitable for many biological applications,such as targeted drug delivery,bioimaging,and tracking of therapeutic agents.According to our previous research,self-assembled fluorescent peptide nanoparticles can overcome the intrinsic optical properties of peptides.However,monochromatic fluorescent nanomaterials have many limitations as luminescent agents in biomedical applications.Therefore,combining different fluorescent species into one nanostructure to prepare fluorescent nanoparticles with multiple emission wavelengths has become a very attractive research area in the bioimaging field.In this study,the tetrapeptide Trp-Trp-Trp-Trp(WWWW)was self-assembled into multicolor fluorescent nanoparticles(TPNPs).The results have demonstrated that TPNPs have the blue,green,red and near infrared(NIR)fluorescence emission wavelength.Moreover,TPNPs have shown excellent performance in multicolor bioimaging,biocompatibility,and photostability.The facile preparation and multicolor fluorescence features make TPNPs potentially useful in multiplex bioanalysis and diagnostics.

The application of biomacromolecules to improve oral absorption by enhanced intestinal permeability:A mini-review

Oral administration has been widely regarded as the most conve nient,quick and safe approach compared to other routes of drug delivery.However,oral absorption of drugs is often limited due to rigorous environments and complex obstacles in gastrointestinal tract.Having received considerable attention,biomacromolecules have been applied for oral drug delivery to improve the bioavailability,which could be attributed to its stability and unique bioactivities,including intestinal adhesion,opening of epithelial tight junctions,inhibiting cell efflux and regulating relative protein expression.Specifically,enhancing intestinal permeability has been regarded as a promising strategy for improving bioavailability of oral drug delivery.In this review,a series of biomacromolecules and the related mechanisms of increasing intestinal permeability for enhanced oral bioavailability are comprehensively classified and elucidated.In addition,recent advances in biomacromolecules based oral delivery and related future directions are mentioned and predicted in this review article.

Self-assembled fluorescent tripeptide nanoparticles for bioimaging and drug delivery applications

Peptide self-assembled nanomaterials have attracted more and more attention due to their wide applications such as drug delive ry,cell imaging,and real-time drug monitoring.However,the application of the peptide is still limited by its inherent optical properties.Here we proposed and prepared a series of fluorescent tripeptide nanoparticles(TPNPs)through π-π stacking and zinc coordination.The experimental results show that the nanoparticles(TPNPs1)formed by the self-assembly of the tripeptide tryptophan-tryptophan-tryptophan have the highest fluorescence intensity,uniform and appropriate size,and low cytotoxicity.Furthermore,there was fluorescence resonance between TPNPs1 and doxorubicin,which has been successfully applied for real-time cell imaging and drug release monitoring.

Detection of amyloid-beta by Fmoc-KLVFF self-assembled fluorescent nanoparticles for Alzheimer’s disease diagnosis

The abnormal aggregation of amyloid-beta(Aβ)has been widely believed to play an important role in the pathogenesis of Alz heimer’s disease(AD),which is also recognized as one of the main biomarkers for AD diagnosis.The peptide sequence Lys-Leu-Val-Phe-Phe(KLVFF)is considered as the main driver of the fibrillation of Aβ,which also can be utilized to target Aβand inhibit its aggregation.In this study,KLVFF and Fmoc-KLVFF fluorescent nanoparticles were self-assembled through zinc coordination andπ-πstacking.The recognition of Aβaggregates including oligomers and fibrils by fluorescent nanoparticles can be realized through aromatic,hydrophobic,and hydrogen-bond interactions.The fluorescent nanoprobes can distinguish Aβaggregation formats and detect Aβat the limit of 1 pg/mL(S/N=3).Hence,the detection of Aβaggregates by fluorescent peptide nanoparticles has great potential for AD diagnosis and progression prediction.

Blood-based Alzheimer’s disease diagnosis using fluorescent peptide nanoparticle arrays

There is a critical need to diagnose and monitor the progression of Alzheimer’s disease(AD) using bloodbased biomarkers. At present, it is believed that tau biomarkers can be utilized to reliably detect AD.Multimodal techniques are highly sought after for AD diagnosis and progression monitoring. For this purpose, we developed a fluorescent peptide nanoparticles(f-PNPs) arrays that is capable of detecting multiple signals simultaneously. The concentration, aggregation stages, and Young’s modulus of tau biomarkers could be analyzed by monitoring the changes of multimodal fluorescence intensity, nano-morphological,and nano-mechanical properties of the f-PNPs arrays. Experimental results indicated that, compared to healthy human, the concentration, Young’s modulus, and aggregation levels of tau proteins in blood samples of clinically diagnosed AD patients increased continuously with the increase of disease severity. The minimally invasive and multimodal characterization techniques showed high signal-to-noise ratio for AD diagnosis.