A New Approach for in vitro Imaging of Breast Cancer Cells by Anti‐Metadherin Targeted PVA‐Pyrene

Poly(vinyl alcohol)‐pyrene‐anti‐metadherin (PVA‐Py‐(Anti‐MTDH)), a novel antibody based water soluble probe containing both fluorescent and target sites in the structure for in vitro imaging of breast cancer cells is reported here. Since breast cancer cells have an excess of MDTH protein expressed on the surface, a PVA‐Py prepared by “Click chemistry” approach is targeted by Anti‐MTDH antibody and applied to the MCF‐7 cell line. After characterization, the designed architecture was evaluated in terms of cell incorporation efficiency and compared with a non‐targeted structure (PVA‐Py). Atomic force microscopy (AFM) and fluorescence microscopy images of cells after incubation of the probe molecules were also obtained to monitor the interaction of the probes with the cancerous cells.

     

From Composition to Cure: A Systems Engineering Approach to Anticancer Drug Carriers

The molecular complexity and heterogeneity of cancer has led to a persistent, and as yet unsolved, challenge to develop cures for this disease. The pharmaceutical industry focuses the bulk of its efforts on the development of new drugs, but an alternative approach is to improve the delivery of existing drugs with drug carriers that can manipulate when, where, and how a drug exerts its therapeutic effect. For the treatment of solid tumors, systemically delivered drug carriers face significant challenges that are imposed by the pathophysiological barriers that lie between their site of administration and their site of therapeutic action in the tumor. Furthermore, drug carriers face additional challenges in their translation from preclinical validation to clinical approval and adoption. Addressing this diverse network of challenges requires a systems engineering approach for the rational design of optimized carriers that have a realistic prospect for translation from the laboratory to the patient.     

Approach to peptide decorated micelles via RAFT polymerization

Pyridyldisulfide (PDS) functionalized telechelic polymers of oligo(ethyleneglycol) acrylate (PEG‐A) and their amphiphilic triblock copolymers with styrene (St) were synthesized directly by reversible addition‐fragmentation chain transfer (RAFT) polymerization using a new bifunctional RAFT agent, S,S‐bis[α,α′‐dimethyl‐α″‐(2‐pyridyl disulfide) ethyl acetate] trithiocarbonate (BDPET). The homopolymerization of PEG‐A was found to be well controlled using BDPET (PDI < 1.2). The ABA triblock copolymers poly(PEG‐A)‐b‐poly(St)‐b‐poly(PEG‐A) with narrow molecular weight distribution (PDI < 1.25) were synthesized using poly(PEG‐A) as a macro‐RAFT agent. UV‐vis spectroscopic analysis revealed that 85 mol % of poly(PEG‐A) and 78 mol % of poly(PEG‐A)‐b‐poly(St)‐b‐poly(PEG‐A) retained PDS end group functionality. Micelles were observed to form from poly(PEG‐A)‐b‐poly(St)‐b‐poly(PEG‐A). The presence of PDS groups within the micelle corona was evidenced by UV‐vis spectroscopy and fluorescence spectroscopy. The PDS groups within the corona were then used to functionalize the micelles with a thiol group bearing model peptide, reduced glutathione, and a thiol modified fluorophore, rhodamine B, under mild reaction conditions. UV‐vis and fluorescence spectrocopies revealed that approximately 80% PDS groups from the amphiphilic copolymer were tethered within the micelle coronas and accessible to glutathione and fluorophore attachment. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 899–912, 2009     

Stereocomplex Polylactide for Drug Delivery and Biomedical Applications: A Review

Polylactide (PLA) is among the most common biodegradable polymers, with applications in various fields, such as renewable and biomedical industries. PLA features poly(D-lactic acid) (PDLA) and poly(L-lactic acid) (PLLA) enantiomers, which form stereocomplex crystals through racemic blending. PLA emerged as a promising material owing to its sustainable, eco-friendly, and fully biodegradable properties. Nevertheless, PLA still has a low applicability for drug delivery as a carrier and scaffold. Stereocomplex PLA (sc-PLA) exhibits substantially improved mechanical and physical strength compared to the homopolymer, overcoming these limitations. Recently, numerous studies have reported the use of sc-PLA as a drug carrier through encapsulation of various drugs, proteins, and secondary molecules by various processes including micelle formation, self-assembly, emulsion, and inkjet printing. However, concerns such as low loading capacity, weak stability of hydrophilic contents, and non-sustainable release behavior remain. This review focuses on various strategies to overcome the current challenges of sc-PLA in drug delivery systems and biomedical applications in three critical fields, namely anti-cancer therapy, tissue engineering, and anti-microbial activity. Furthermore, the excellent potential of sc-PLA as a next-generation polymeric material is discussed.     

A General Approach to Enzyme-Responsive Liposomes

Liposomes are effective nanocarriers due to their ability to deliver encapsulated drugs to diseased cells. Nevertheless, liposome delivery would be improved by enhancing the ability to control the release of contents at the target site. While various stimuli have been explored for triggering liposome release, enzymes provide excellent targets due to their common overexpression in diseased cells. We present a general approach to enzyme-responsive liposomes exploiting targets that are commonly aberrant in disease, including esterases, phosphatases, and β-galactosidases. Responsive lipids correlating with each enzyme family were designed and synthesized bearing an enzyme substrate moiety attached via a self-immolating linker to a non-bilayer lipid scaffold, such that enzymatic hydrolysis triggers lipid decomposition to disrupt membrane integrity and release contents. Liposome dye leakage assays demonstrated that each enzyme-responsive liposome yielded significant content release upon enzymatic treatment compared to minimal release in controls. Results also showed that fine-tuning liposome composition was critical for controlling release. DLS analysis showed particle size increases in the cases of esterase- and β-galactosidase-responsive lipids, supporting alterations to membrane properties. These results showcase an effective modular strategy that can be tailored to target different enzymes, providing a promising new avenue for advancing liposomal drug delivery.     

Application of Dendrimers in Anticancer Diagnostics and Therapy

The application of dendrimeric constructs in medical diagnostics and therapeutics is increasing. Dendrimers have attracted attention due to their compact, spherical three-dimensional structures with surfaces that can be modified by the attachment of various drugs, hydrophilic or hydrophobic groups, or reporter molecules. In the literature, many modified dendrimer systems with various applications have been reported, including drug and gene delivery systems, biosensors, bioimaging contrast agents, tissue engineering, and therapeutic agents. Dendrimers are used for the delivery of macromolecules, miRNAs, siRNAs, and many other various biomedical applications, and they are ideal carriers for bioactive molecules. In addition, the conjugation of dendrimers with antibodies, proteins, and peptides allows for the design of vaccines with highly specific and predictable properties, and the role of dendrimers as carrier systems for vaccine antigens is increasing. In this work, we will focus on a review of the use of dendrimers in cancer diagnostics and therapy. Dendrimer-based nanosystems for drug delivery are commonly based on polyamidoamine dendrimers (PAMAM) that can be modified with drugs and contrast agents. Moreover, dendrimers can be successfully used as conjugates that deliver several substances simultaneously. The potential to develop dendrimers with multifunctional abilities has served as an impetus for the design of new molecular platforms for medical diagnostics and therapeutics.     

Biofuel Cells for Self‐Powered Electrochemical Biosensing and Logic Biosensing: A Review

This article reviews recent advances and progress in developing electrochemical (EC) biosensing and logic biosensing systems based on self‐powered biofuel cells (BFCs). BFCs that exploit enzymes and microbes have attracted a considerable recent interest owing to their unique ability to provide sustainable energy from renewable fuel source under mild conditions. This review focuses on recently introduced novel concepts for using BFCs as the basic element for EC‐biosensing and especially EC‐logic biosensing applications. The fabrication and design of such self‐powered EC‐biosensing and EC‐logic biosensing are described along and different new approaches for BFCs‐based EC‐biosensing and EC‐logic biosensing involving substrate effects, inhibition effects, blocking effects and gene regulation effects. Latest advances in coupling a self‐powered diagnostic operation with logic‐activated drug release functionality are discussed. We conclude with the implications of the new self‐powered biosensing/logic‐biosensing platforms along with future prospects and challenges.     

Synthesis,Chemical–Physical Characterization,and Biomedical Applications of Functional Gold Nanoparticles: A Review

Relevant properties of gold nanoparticles, such as stability and biocompatibility, together with their peculiar optical and electronic behavior, make them excellent candidates for medical and biological applications. This review describes the different approaches to the synthesis, surface modification, and characterization of gold nanoparticles (AuNPs) related to increasing their stability and available features useful for employment as drug delivery systems or in hyperthermia and photothermal therapy. The synthetic methods reported span from the well-known Turkevich synthesis, reduction with NaBH₄ with or without citrate, seeding growth, ascorbic acid-based, green synthesis, and Brust–Schiffrin methods. Furthermore, the nanosized functionalization of the AuNP surface brought about the formation of self-assembled monolayers through the employment of polymer coatings as capping agents covalently bonded to the nanoparticles. The most common chemical–physical characterization techniques to determine the size, shape and surface coverage of AuNPs are described underlining the structure–activity correlation in the frame of their applications in the biomedical and biotechnology sectors.     

Chitosan Nanoparticles-Insight into Properties,Functionalization and Applications in Drug Delivery and Theranostics

Nanotechnology-based development of drug delivery systems is an attractive area of research in formulation driven R&D laboratories that makes administration of new and complex drugs feasible. It plays a significant role in the design of novel dosage forms by attributing target specific drug delivery, controlled drug release, improved, patient friendly drug regimen and lower side effects. Polysaccharides, especially chitosan, occupy an important place and are widely used in nano drug delivery systems owing to their biocompatibility and biodegradability. This review focuses on chitosan nanoparticles and envisages to provide an insight into the chemistry, properties, drug release mechanisms, preparation techniques and the vast evolving landscape of diverse applications across disease categories leading to development of better therapeutics and superior clinical outcomes. It summarizes recent advancement in the development and utility of functionalized chitosan in anticancer therapeutics, cancer immunotherapy, theranostics and multistage delivery systems.     

碳纳米管在药物和基因转运领域的研究进展

当前,国内外的许多研究小组都致力于开发出新型有效的药物和基因转运系统,用于改善多种治疗因子的药理学作用并降低其毒性。在纳米材料这一类中,碳纳米管（Carbon Nanotubes, CNTs）正逐步引起人们的关注。功能化的CNTs的两个关键优势在于它具有很强的细胞穿透能力和较低的细胞毒性,使其在药物和基因转运领域中的应用成为可能。CNTs可通过形成稳定的共价键或形成以非共价键为基础的超分子结合物来运载肽类、蛋白质、核酸和药物等活性分子,并将其运送至特定的组织、器官中以表达特殊的生物学功能。针对这一研究热点,本文综述了近几年国内外关于碳纳米管在药物和基因转运领域中的应用进展,并探讨了其毒性,以期为这一领域中的研究工作者提供参考。     

Exosomes as New Generation Vehicles for Drug Delivery: Biomedical Applications and Future Perspectives

Currently, particular interest among the scientific community is focused on exploring the use of exosomes for several pharmaceutical and biomedical applications. This is due to the identification of the role of exosomes as an excellent intercellular communicator by delivering the requisite cargo comprising of functional proteins, metabolites and nucleic acids. Exosomes are the smallest extracellular vesicles (EV) with sizes ranging from 30–100 nm and are derived from endosomes. Exosomes have similar surface morphology to cells and act as a signal transduction channel between cells. They encompass different biomolecules, such as proteins, nucleic acids and lipids, thus rendering them naturally as an attractive drug delivery vehicle. Like the other advanced drug delivery systems, such as polymeric nanoparticles and liposomes to encapsulate drug substances, exosomes also gained much attention in enhancing therapeutic activity. Exosomes present many advantages, such as compatibility with living tissues, low toxicity, extended blood circulation, capability to pass contents from one cell to another, non-immunogenic and special targeting of various cells, making them an excellent therapeutic carrier. Exosome-based molecules for drug delivery are still in the early stages of research and clinical trials. The problems and clinical transition issues related to exosome-based drugs need to be overcome using advanced tools for better understanding and systemic evaluation of exosomes. In this current review, we summarize the most up-to-date knowledge about the complex biological journey of exosomes from biogenesis and secretion, isolation techniques, characterization, loading methods, pharmaceutical and therapeutic applications, challenges and future perspectives of exosomes.     

从层层组装的核壳粒子到医学/生物化学诊断和药物输送*

层层组装的核壳型粒子由于具有尺度和组成的剪裁优点近年来得到了广泛的研究,它们为技术应用如医学/生物化学诊断和药物输送提供了新的机遇.本文综述了基于层层自组装和胶体模板以及采用各种化学和物理方法直接除去核制备磁性复合核壳粒子和空腔球体.给出了核壳粒子在药物输送、生物检测与标记应用的一些实例.     

Alginate Bioconjugate and Graphene Oxide in Multifunctional Hydrogels for Versatile Biomedical Applications

In this work, we combined electrically-conductive graphene oxide and a sodium alginate-caffeic acid conjugate, acting as a functional element, in an acrylate hydrogel network to obtain multifunctional materials designed to perform multiple tasks in biomedical research. The hybrid material was found to be well tolerated by human fibroblast lung cells (MRC-5) (viability higher than 94%) and able to modify its swelling properties upon application of an external electric field. Release experiments performed using lysozyme as the model drug, showed a pH and electro-responsive behavior, with higher release amounts and rated in physiological vs. acidic pH. Finally, the retainment of the antioxidant properties of caffeic acid upon conjugation and polymerization processes (Trolox equivalent antioxidant capacity values of 1.77 and 1.48, respectively) was used to quench the effect of hydrogen peroxide in a hydrogel-assisted lysozyme crystallization procedure.     

Dendritic Polymers in Biomedical Applications: From Potential to Clinical Use in Diagnostics and Therapy

Dendrimers are characterized by a combination of high end‐group functionality and a compact, precisely defined molecular structure. These characteristics can be used in biomedical applications, for example, for the amplification or multiplication of effects on a molecular level, or to create extremely high local concentrations of drugs, molecular labels, or probe moieties. A brief summary of the current state of the art in the field is given, and focuses on the application of dendrimers both in diagnostics as well as in therapy. In diagnostics, dendrimers that bear Gd^III complexes are used as contrast agents in magnetic resonance imaging. DNA dendrimers have potential for routine use in high‐throughput functional genomic analysis, as well as for DNA biosensors. Dendrimers are also being investigated for therapeutics, for example, as carriers for controlled drug delivery, in gene transfection, as well as in boron neutron‐capture therapy. Furthermore, the antimicrobial activity of dendrimers has been studied.     

Nanomaterials for Biomedical Applications: Production,Characterisations, Recent Trends and Difficulties

Designing of nanomaterials has now become a top-priority research goal with a view to developing specific applications in the biomedical fields. In fact, the recent trends in the literature show that there is a lack of in-depth reviews that specifically highlight the current knowledge based on the design and production of nanomaterials. Considerations of size, shape, surface charge and microstructures are important factors in this regard as they affect the performance of nanoparticles (NPs). These parameters are also found to be dependent on their synthesis methods. The characterisation techniques that have been used for the investigation of these nanomaterials are relatively different in their concepts, sample preparation methods and obtained results. Consequently, this review article aims to carry out an in-depth discussion on the recent trends on nanomaterials for biomedical engineering, with a particular emphasis on the choices of the nanomaterials, preparation methods/instruments and characterisations techniques used for designing of nanomaterials. Key applications of these nanomaterials, such as tissue regeneration, medication delivery and wound healing, are also discussed briefly. Covering this knowledge gap will result in a better understanding of the role of nanomaterial design and subsequent larger-scale applications in terms of both its potential and difficulties.     

Switching it Up: The Promise of Stimuli-Responsive Polymer Systems in Biomedical Science

Responsive polymer systems have the ability to change properties or behavior in response to external stimuli. The properties of responsive polymer systems can be fine-tuned by adjusting the stimuli, enabling tailored responses for specific applications. These systems have applications in drug delivery, biosensors, tissue engineering, and more, as their ability to adapt and respond to dynamic environments leads to improved performance. However, challenges such as synthesis complexity, sensitivity limitations, and manufacturing issues need to be addressed for successful implementation. In our review, we provide a comprehensive summary on stimuli-responsive polymer systems, delving into the intricacies of their mechanisms and actions. Future developments should focus on precision medicine, multifunctionality, reversibility, bioinspired designs, and integration with advanced technologies, driving the dynamic growth of sensitive polymer systems in biomedical applications.     

Reflux Precipitation Polymerization: A New Platform for the Preparation of Uniform Polymeric Nanogels for Biomedical Applications

Reflux precipitation polymerization (RPP) represents an effective approach that enables to prepare various types of polymeric nanogels with precise control over the morphology and structure. Owing to facile loading or modification by a variety of functional moieties, rationally designed nanogels pose the possibility to attain a platform for tailoring functional properties that could be widely used for various biomedical applications, such as multifunctional drug delivery, enrichment of functional peptides, separation of specific proteins, as well as detection of circulating tumor cells. This feature article highlights RPP as a promising polymerization strategy that provides access to facile generation of modular nanostructures or multifunctional properties in a diverse range of biomedical applications, proving that RPP has great potential to become one of the most attractive polymerization techniques in polymer chemistry.     

Drug Encapsulation and Release by Mesoporous Silica Nanoparticles: The Effect of Surface Functional Groups

Mesoporous silica nanoparticles (MSNPs) have been widely used as drug carriers for stimuli‐responsive drug delivery. Herein, a catalysis screening technique was adopted for analyzing the effects of chain length, terminal group, and density of disulfide‐appended functional ligands on the surface of MSNPs on drug‐loading capacity and glutathione‐triggered drug‐release kinetics. The ligand with an intermediate length (5 carbon atoms) and a bulky terminal group (cyclohexyl) that complexes with theβ‐cyclodextrin ring showed the highest drug loading capacity as well as good release kinetics. In addition, decreasing the surface coverage of the functional ligands led to an enhancement in drug release. In vitro drug‐delivery experiments on a melanoma cell line (B16‐F10) by using the functionalized MSNPs further supported the conclusion. The results obtained may serve as a general guide for developing more effective MSNP systems for drug delivery.     

Recent Progress on the Development of Biofuel Cells for Self‐Powered Electrochemical Biosensing and Logic Biosensing: A Review

Biofuel cells (BFCs) based on enzymes and microorganisms have been recently received considerable attention because they are recognized as an attractive type of energy conversion technology. In addition to the research activities related to the application of BFCs as power source, we have witnessed recently a growing interest in using BFCs for self‐powered electrochemical biosensing and electrochemical logic biosensing applications. Compared with traditional biosensors, one of the most significant advantages of the BFCs‐based self‐powered electrochemical biosensors and logic biosensors is their ability to detect targets integrated with chemical‐to‐electrochemical energy transformation, thus obviating the requirement of external power sources. Following my previous review (Electroanalysis­ 2012 , 24, 197–209), the present review summarizes, discusses and updates the most recent progress and latest advances on the design and construction of BFCs‐based self‐powered electrochemical biosensors and logic biosensors. In addition to the traditional approaches based on substrate effect, inhibition effect, blocking effect and gene regulation effect for BFCs‐based self‐powered electrochemical biosensors and logic biosensors design, some new principles including enzyme effect, co‐stabilization effect, competition effect and hybrid effect are summarized and discussed by me in details. The outlook and recommendation of future directions of BFCs‐based self‐powered electrochemical biosensors and logic biosensors are discussed in the end.