Gold Nanoparticles for Cancer Theranostics

Gold nanoparticles have seen unprecedented development in the biomedical field, particularly for cancer therapy. They have received extensive attention because of their easy preparation, functionalization, biocompatibility, non‐cytotoxicity, and detectability. Functionalized gold nanoparticles can be applied in the fields of drug and gene delivery, photothermal therapy, and bioimaging. This review introduces methods for preparing various shapes of gold nanoparticles and describes their current applications in the field of cancer treatment. Moreover, the review presents the development routes and current issues of gold nanoparticles in clinical theranostics.     

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.     

Chitosan-based nanocomposites for medical applications

Chitosan as a biobased polymer is gaining increasing attention due to its extraordinary physico-chemical characteristics and properties. While a primary use of chitosan has been in horticultural and agricultural applications for plant defense and to increase crop yield, recent research reports display various new utilizations in the field of advanced biomedical devices, targeted drug delivery, and as bioimaging sensors. Chitosan possesses multiple characteristics such as antimicrobial properties, stimuli-responsiveness, tunable mechanical strength, biocompatibility, biodegradability, and water-solubility. Further, chitosan can be processed into nanoparticles, nano-vehicles, nanocapsules, scaffolds, fiber meshes, and 3D printed scaffolds for a variety of applications. In recent times, nanoparticles incorporated in chitosan matrices have been identified to show superior biological activity, as cells tend to proliferate/differentiate faster when they interact with nanocomposites rather than bulk or micron size substrates/scaffolds. The present article intents to cover chitosan-based nanocomposites used for regenerative medicine, wound dressings, drug delivery, and biosensing applications.     

A perspective on bioconjugated nanoparticles and quantum dots

Bioconjugated nanoparticles and quantum dots are among the most exciting nanomaterials with promising application potentials in nanomedicine field. These applications include biosensing, bioimaging, bioassay, targeted drug delivery and new therapeutic agents or method development. Although most of these applications are based on the optical properties of nanoparticle materials such as surface plasmon resonance, surface enhanced Raman scattering and strong photoluminescence, other aspects of nanoparticles such as the catalytic effect and amplification effect associated with the nanoscale dimension have also been explored. This review presents a narrative summary on the use of bioconjugated nanoparticles and quantum dots for biological applications, along with a discussion on some critical challenges existing in the field and possible solutions that have been or are being developed to overcome these challenges.     

Use of Polyhedral Oligomeric Silsesquioxane (POSS) in Drug Delivery,Photodynamic Therapy and Bioimaging

Polyhedral oligomeric silsesquioxanes (POSS) have attracted considerable attention in the design of novel organic-inorganic hybrid materials with high performance capabilities. Features such as their well-defined nanoscale structure, chemical tunability, and biocompatibility make POSS an ideal building block to fabricate hybrid materials for biomedical applications. This review highlights recent advances in the application of POSS-based hybrid materials, with particular emphasis on drug delivery, photodynamic therapy and bioimaging. The design and synthesis of POSS-based materials is described, along with the current methods for controlling their chemical functionalization for biomedical applications. We summarize the advantages of using POSS for several drug delivery applications. We also describe the current progress on using POSS-based materials to improve photodynamic therapies. The use of POSS for delivery of contrast agents or as a passivating agent for nanoprobes is also summarized. We envision that POSS-based hybrid materials have great potential for a variety of biomedical applications including drug delivery, photodynamic therapy and bioimaging.     

Optical/Magnetic Multimodal Bioprobes Based on Lanthanide‐Doped Inorganic Nanocrystals

Multimodal bioprobes, which integrate the advantages of different diagnostic modes into one single particle, can overcome the current limitations of sensitivity and resolution in medical assays and significantly improve the outcome of existing therapeutics. Lanthanide‐doped inorganic multimodal bioprobes, which are emerging as a promising new class of optical/magnetic multimodal bioprobes, have been long sought‐after and have recently attracted revived interest owing to their distinct optical and magnetic properties. In this concept article, we introduce the controlled synthesis of lanthanide‐doped inorganic multimodal bioprobes, including core–shell structured and single‐phase nanoparticles, and demonstrate different design strategies for achieving dual‐modal functionalization of nanoprobes. In particular, we highlight the most recent advances in biodetection, bioimaging, targeted drug delivery, and therapy based on these nanoparticles.     

Surface-modulated and thermoresponsive polyphosphoesternanoparticles for enhanced intracellular drug delivery

The chemical structure of end groups influenced the phase transition temperature of thermoresponsive polymers. We demonstrated a strategy for the preparation of the pH/thermo-responsive polymeric nanoparticles via subtle modification of end groups of thermoresponsive polymer segments with a carboxyl group and revealed its potential application for enhanced intracellular drug delivery. By developing a polymeric nanoparticle composed of poly(aliphatic ester) as the inner core and thermoresponsive polyphosphoester as the outer shell, we showed that end groups of thermoresponsive polyphosphoester segments modified by carboxyl groups exhibited a pH/thermo-responsive behavior due to the hydrophilic to hydrophobic transitions of the end groups in response to the pH. Moreover, by encapsulating doxorubicin into the hydrophobic core of such pH/thermo-responsive polymer nanoparticles, their intracellular delivery and cytotoxicity to wild-type and drug-resistant tumor cells were significantly enhanced through the phase-transition-dependent drug release that was triggered by endosomal/lysosomal pH. This novel strategy and the multi-responsive polymer nanoparticles achieved by the subtle chain-terminal modification of thermoresponsive polymers provide a smart platform for biomedical applications.     

Strategies toward well‐defined polymer nanoparticles inspired by nature: Chemistry versus versatility

Polymeric nanoparticles are promising delivery platforms for various biomedical applications. One of the main challenges toward the development of therapeutic nanoparticles is the premature disassembly and release of the encapsulated drug. Among the different strategies to enhance the kinetic stability of polymeric nanoparticles, shell‐ and core‐crosslinking have been shown to provide robust character, while creating a suitable environment for encapsulation of a wide range of therapeutics, including hydrophilic, hydrophobic, metallic, and small and large biomolecules, with gating of their release as well. The versatility of shell‐ and core‐crosslinked nanoparticles is driven from the ease by which the structures of the shell‐ and core‐forming polymers and crosslinkers can be modified. In addition, postmodification with cell‐recognition moieties, grafting of antibiofouling polymers, or chemical degradation of the core to yield nanocages allow the use of these robust nanostructures as “smart” nanocarriers. The building principles of these multifunctional nanoparticles borrow analogy from the synthesis, supramolecular assembly, stabilization, and dynamic activity of the naturally driven biological nanoparticles such as proteins, lipoproteins, and viruses. In this review, the chemistry involved during the buildup from small molecules to polymers to covalently stabilized nanoscopic objects is detailed, with contrast of the strategies of the supramolecular assembly of polymer building blocks followed by intramicellar stabilization into shell‐, core‐, or core–shell‐crosslinked knedel‐like nanoparticles versus polymerization of polymers into nanoscopic molecular brushes followed by further intramolecular covalent stabilization events. The rational design of shell‐crosslinked knedel‐like nanoparticles is then elaborated for therapeutic packaging and delivery, with emphasis on the polymer chemistry aspects to accomplish the synthesis of such nanoparticulate systems. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Droplet‐based microfluidics systems in biomedical applications

Microfluidics has made a very impressive progress in the past decades due to its unique and instinctive advantages. Droplet‐based microfluidic systems show excellent compatibility with many chemical and biological reagents and are capable of performing variety of operations that can implement microreactor, complex multiple core–shell structure, and many applications in biomedical research such as drug encapsulation, targeted drug delivery systems, and multifunctionalization on carriers. Droplet‐based systems have been directly used to synthesize particles and encapsulate many biological entities for biomedicine applications due to their powerful encapsulation capability and facile versatility. In this paper, we review its origin, deviation, and evolution to draw a clear future, especially for droplet‐based biomedical applications. This paper will focus on droplet generation, variations and complication as starter, and logistically lead to the numerous typical applications in biomedical research. Finally, we will summarize both its challenge and future prospects relevant to its droplet‐based biomedical applications.     

多功能金属石墨纳米囊的生物医学应用进展

多功能金属石墨纳米囊由于其良好的稳定性和独特的理化性质, 在生物医学领域受到了广泛关注. 利用石墨烯外壳独特的拉曼散射特征峰作为拉曼标签或者内标, 结合等离子体纳米核优异的表面增强拉曼散射(SERS)和双光子发光(TPL)性能, 可实现SERS生物分析以及肿瘤细胞或组织的Raman/TPL双模成像. 利用表面积大的石墨烯外壳作为药物负载平台, 结合等离子体纳米核的近红外光吸收能力, 可实现光介导的病原菌杀灭以及肿瘤细胞或实体瘤的热疗与化疗的协同治疗. 此外, 利用石墨烯外壳优异的荧光猝灭性能, 还实现了生物分子的荧光检测; 利用磁性纳米核独特的磁学性能, 可实现生物样品的分离和富集、 细菌的原位磁共振成像检测以及磁靶向胃部口服药物的递送. 本综述首先介绍了金属石墨纳米囊的制备、 分类和性质, 然后概述了它们在生物检测、 生物成像和治疗3个方面的应用进展, 并进一步总结了它们的发展现状包括生物毒性和生物医学应用的优缺点, 最后对其在生物医学领域的发展方向做出了展望. 我们期望多功能的金属石墨纳米囊能够为今后的临床生物医学应用提供可靠的纳米平台.     

Surface Modification of Functional Nanoparticles for Controlled Drug Delivery

Abstract

Surface‐modified nanoparticles have received much attention as drug carriers. Natural and synthetic polymers are used as the materials to prepare nanoparticles and the properties of these nanoparticles originate with these polymeric materials. In particular, these nanoparticles are modified for specific objectives. The surface characteristics of (shell) nanoparticles are more important than those of the core, because the shell layer directly contacts body fluids and organs. Generally, the nanoparticles are coated with hydrophilic polymer to give long circulation and/or are conjugated with functional ligands or proteins for site‐specific delivery. In this review, the preparative methods and the applications of surface modification of polymeric functionalized nanoparticles for long‐circulation, site‐specific delivery, and oral delivery are discussed.     

Recent advances in surface engineering of superparamagnetic iron oxide nanoparticles for biomedical applications

Superparamagnetic iron oxide nanoparticles (SPIONs) are promising materials for various biomedical applications including targeted drug delivery and imaging, hyperthermia, magneto-transfections, gene therapy, stem cell tracking, molecular/cellular tracking, magnetic separation technologies (e.g. rapid DNA sequencing), and detection of liver and lymph node metastases. The most recent applications for SPIONs for early detection of inflammatory, cancer, diabetes and atherosclerosis have also increased their popularity in academia. In order to increase the efficacy of SPIONs in the desired applications, especial surface coating/characteristics are required. The aim of this article is to review the surface properties of magnetic nanoparticles upon synthesis and the surface engineering by different coatings. The biological aspects, cytotoxicity, and health risks are addressed. Special emphasis is given to organic and inorganic-based coatings due to their determinant role in biocompatibility or toxicity of the final particles.     

Bioimaging Based on Nucleic Acid Nanostructures

Nucleic acid nanostructures with structural programmability, spatial addressability and excellent biocompatibility have drawn much attention in various biomedical applications, such as bioimaging, biosensing and drug delivery. In this review, we summarize the recent research progress in the field of bioimaging based on nucleic acid nanostructures with different imaging models, including fluorescent imaging(FI), magnetic resonance imaging(MRI), photoacoustic imaging(PAI) and positron emission tomography/computed tomography(PET/CT) imaging. We also discuss the remaining challenges and further opportunities involved in the bioimaging research based on nucleic acid nanostructures.     

Emulsion Techniques for the Production of Pharmacological Nanoparticles

Nanoparticles have the advantages over micron‐sized particles to typically provide higher intracellular uptake and drug bioavailability. Emulsion techniques are commonly used methods for producing nanoparticles aiming at high encapsulation efficiency, high stability, and low toxicity. Here, the recent developments of nanoparticles prepared from emulsions, the synthesis of nanoparticles, their physicochemical properties, and their biomedical applications are discussed. Selection of techniques, such as emulsion polymerization, miniemulsion polymerization, microemulsion polymerization, and emulsion‐solvent evaporation processes, strongly influences morphologies, size distributions, and particle properties. Details in the synthetic strategies governing the performance of nanoparticles in bioimaging, biosensing, and drug delivery are presented. Benefits and limitations of molecular imaging techniques are also discussed.     

Mesoporous silica nanoparticles for 19F magnetic resonance imaging,fluorescence imaging,and drug delivery

Multifunctional mesoporous silica nanoparticles (MSNs) are good candidates for multimodal applications in drug delivery, bioimaging, and cell targeting. In particular, controlled release of drugs from MSN pores constitutes one of the superior features of MSNs. In this study, a novel drug delivery carrier based on MSNs, which encapsulated highly sensitive ¹⁹F magnetic resonance imaging (MRI) contrast agents inside MSNs, was developed. The nanoparticles were labeled with fluorescent dyes and functionalized with small molecule-based ligands for active targeting. This drug delivery system facilitated the monitoring of the biodistribution of the drug carrier by dual modal imaging (NIR/¹⁹F MRI). Furthermore, we demonstrated targeted drug delivery and cellular imaging by the conjugation of nanoparticles with folic acid. An anticancer drug (doxorubicin, DOX) was loaded in the pores of folate-functionalized MSNs for intracellular drug delivery. The release rates of DOX from the nanoparticles increased under acidic conditions, and were favorable for controlled drug release to cancer cells. Our results suggested that MSNs may serve as promising ¹⁹F MRI-traceable drug carriers for application in cancer therapy and bio-imaging.     

Biocompatible poly(ethylene glycol)‐poly(γ‐cholesterol‐L‐glutamate) copolymers: Synthesis,characterization, and in vitro studies

A novel amphiphilic poly(ethylene glycol)‐block‐poly(γ‐cholesterol‐L ‐glutamate) (mPEG–PCHLG) diblock copolymer has been synthesized. The mPEG–PCHLG copolymer has good biocompatibility and low toxicity. The mPEG–PCHLG copolymers could aggregate into nanoparticles with PCHLG blocks as the hydrophobic core and PEG blocks as the hydrophilic shell through emulsion solvent evaporation method. The copolymers were characterized by nuclear magnetic resonance spectroscopy, mass spectrum, Fourier transform infrared spectroscopy, and gel permeation chromatography. The particle sizes, size distributions, and zeta potentials of nanoparticles can also be determined by dynamic light scattering and transmission electron microscopy. This work provides a new and facile approach to prepare amphiphilic block copolymer nanoparticles with controllable performances. This novel copolymer may have potential applications in drug delivery and bioimaging applications.© 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Self-Assembled Plasmonic Vesicles of SERS-Encoded Amphiphilic Gold Nanoparticles for Cancer Cell Targeting and Traceable Intracellular Drug Delivery

We report the development of bioconjugated plasmonic vesicles assembled from SERS-encoded amphiphilic gold nanoparticles for cancer-targeted drug delivery. This new type of plasmonic assemblies with a hollow cavity can play multifunctional roles as delivery carriers for anticancer drugs and SERS-active plasmonic imaging probes to specifically label targeted cancer cells and monitor intracellular drug delivery. We have shown that the pH-responsive disassembly of the plasmonic vesicle, stimulated by the hydrophobic-to-hydrophilic transition of the hydrophobic brushes in acidic intracellular compartments, allows for triggered intracellular drug release. Because self-assembled plasmonic vesicles exhibit significantly different plasmonic properties and greatly enhanced SERS intensity in comparison with single gold nanoparticles due to strong interparticle plasmonic coupling, disassembly of the vesicles in endocytic compartments leads to dramatic changes in scattering properties and SERS signals, which can serve as independent feedback mechanisms to signal cargo release from the vesicles. The unique structural and optical properties of the plasmonic vesicle have made it a promising platform for targeted combination therapy and theranostic applications by taking advantage of recent advances in gold nanostructure based in vivo bioimaging and photothermal therapy and their loading capacity for both hydrophilic (nucleic acids and proteins) and hydrophobic (small molecules) therapeutic agents.     

Biomedical application and hidden toxicity of Zinc oxide nanoparticles

Zinc oxide nanoparticles (ZnO NPs) represent a novel type of metal oxide nanoparticles enabling a new horizon for biomedical applications spanning from diagnosis to treatment. ZnO NPs are extensively used in commercial products such as sunscreens and daily-care products. Apart from that, ZnO NPs are used in food packaging and ointments and as an antimicrobial and antifungal agent. They are extensively used for many biomedical applications noticeably in pharmaceutics and theranostics. Its exceptional optical, electrical, and physiochemical properties, notably its incredible surface chemistry, make ZnO NPs a reliable option for bioimaging, biosensors, antimicrobial action, and drug and gene delivery. The present review covers findings and developments in ZnO NPs research in relation to its application and toxicity mechanism. A special emphasis has been given to the neurotoxic potential of the ZnO NPs and glial cell toxicity. Various factors contributing to the toxic potential of ZnO NPs and cell signaling pathways concerning its toxicity are also discussed. Available data point toward the risk of uncontrollable use of zinc nanoformulation. With increasing use, ZnO NPs pose a severe threat both to the ecosystem and human beings. In a nutshell, the review outlines the current state of the art of ZnO NPs.     

Versatile metal graphitic nanocapsules for SERS bioanalysis

A comprehensive summary toward the unique properties of the novel graphitic nanomaterial of metal graphitic nanocapsules (MGNs) and their applications in SERS biodetection and bioimaging were presented here.     

Advances in Intelligent Stimuli-Responsive Microneedle for Biomedical Applications

Microneedles (MNs) are a new type of drug delivery method that can be regarded as an alternative to traditional transdermal drug delivery systems. Recently, MNs have attracted widespread attention for their advantages of effectiveness, safety, and painlessness. However, the functionality of traditional MNs is too monotonous and limits their application. To improve the efficiency of disease treatment and diagnosis by combining the advantages of MNs, the concept of intelligent stimulus-responsive MNs is proposed. Intelligent stimuli-responsive MNs can exhibit unique biomedical functions according to the internal and external environment changes. This review discusses the classification and principles of intelligent stimuli-responsive MNs, such as magnet, temperature, light, electricity, reactive oxygen species, pH, glucose, and protein. This review also highlights examples of intelligent stimuli-responsive MNs for biomedical applications, such as on-demand drug delivery, tissue repair, bioimaging, detection and monitoring, and photothermal therapy. These intelligent stimuli-responsive MNs offer the advantages of high biocompatibility, targeted therapy, selective detection, and precision treatment. Finally, the prospects and challenges for the application of intelligent stimuli-responsive MNs are discussed.