A new era for cancer treatment: gold-nanoparticle-mediated thermal therapies

Nanotechnology-based cancer treatment approaches potentially provide localized, targeted therapies that aim to enhance efficacy, reduce side effects, and improve patient quality of life. Gold-nanoparticle-mediated hyperthermia shows particular promise in animal studies, and early clinical testing is currently underway. In this article, the rapidly evolving field of gold nanoparticle thermal therapy is reviewed, highlighting recent literature and describing current challenges to clinical translation of the technology.     

Polymeric nanospheres fabricated with natural emulsifiers for clinical administration of an anticancer drug paclitaxel (Taxol®)

Paclitaxel (Taxol®) is one of the most effective anticancer drugs found from nature in recent decades, which can treat various cancers including ovarian, breast, brain, colon and lung cancer, and AIDS-related cancer. Due to its low aqueous solubility, adjuvants such as Cremophor EL, which causes serious side effects, have to be used in its administration. Our aim is to develop an alternative delivery system to achieve better therapeutic effects with minimum side effects. Paclitaxel-loaded nanospheres of biodegradable polymers were prepared by an improved solvent extraction/evaporation technique. Phospholipids, cholesterol and vitamins were used to replace traditional chemical emulsifiers to achieve high encapsulation efficiency (EE) and desired release rate of the drug. Nanospheres prepared under various conditions are characterized by the light scattering for size and size distribution, the scanning electron microscopy (SEM) and the atomic force microscopy (AFM) for surface morphology; differential scanning calorimetry (DSC) for the physical status of the drug within the polymeric matrix; the zeta-potential measurement for the surface charge properties; and X-ray photoelectron spectroscopy (XPS) for the surface chemistry. In-vitro release kinetics were measured by high-performance liquid chromatography (HPLC). Best design was pursued to develop a product for cancer chemotherapy.     

Enhancement of gene transfer to cervical cancer cells using transferrin-conjugated liposome

Transferrin-conjugated cationic liposome (T_f -DDAB liposome) was developed as a targeted gene delivery system by using heterobifunctional cross-linking agent, N-succimidyl-3-(2-pyridyldithio)propionate (SPDP), and gradient metrizamide ultracentrifugation method. Physico-chemical properties of T_f -liposome were determined by scanning/transmission electron microscopy (SEM/TEM) and dynamic laser-light scattering method (DLS) with a mean diameter of 584±15 nm. Gel retardation assay was performed using various DDAB:DNA ratios, and proved that the 6:1 weight ratio formulation gave the most neutralized complex. In vitro transfection was done in human cervical cancer cells, HeLa, and the transfection efficiency of T_f -liposome was found to be fivefold higher than that of unconjugated (plain) DDAB liposome and twofold higher than that of Lipofectin™. In conclusion, a target-oriented T_f -DDAB liposome was made successfully and proved to be very efficient in DNA delivery into the cervical cancer cells in culture.     

Upconversion nano-particles from synthesis to cancer treatment: A review

Among many methods to fabricate drugs, Upconversion seems to be an appropriate approach in order to treat cancer with almost no side effects. Upconversion is able to effectively convert two or more low energy photons into the higher energy photons. Since the traditional process of the drug circulation in the biological environment leaves the individuals with many side effects, the translation of the drug to the tumor site is one of the imperative concerns. Because of the capability of the light source in the activation of the fabricated drug in the upconversion process, the photodynamic therapy has attracted a wide range of researchers.There are some approaches to overcome the side effects of cancer therapy. One of the most efficient approaches is the fabrication of biomaterials in the form of micro or nano-capsules. In the upconversion method, it is possible to fabricate a core-shell complex to achieve better yield. In this method, drug can be encapsulated into the core with the size of nano or micro. The structure of the shell in this complex is usually sensitive to the internal or external stimuli as pH or temperature difference. Subsequently, the shell structure would be damaged due to this sensitivity and finally the drug can be released from the core into the targeted site. Moreover, there is an immense interest to develop cancer therapy in the form of the combination therapy which is employing drugs with different working mechanisms and diminishing the probability that resistant cancer cells will grow. In summary, this review article firstly introduces the main methods of the fabrication of upconversion nanoparticles. Then, the application of these particles in different types of cancer therapy including combined therapy is discussed. Moreover, the main drugs applicable in the cancer therapy and their effects in the fabrication of upconversion nanoparticles and complexes are presented.     

Synthesis of nanomedicines by nanohybrids conjugating ginsenosides with auto-targeting and enhanced MRI contrast for liver cancer therapy

A new methodology has been developed with conjugating nanoparticles (NPs) with an active ingredient of Chinese herbs for nanomedicines with auto-targeting and enhanced magnetic resonance imaging (MRI) for liver cancer therapy. Fe@Fe₃O₄ NPs are first synthesized via the programed microfluidic process, whose surfaces are first modified with –NH₂ groups using a silane coupling technique that uses (3-aminopropyl)trimethoxysilane (APTMS) as the coupling reagent and are subsequently activated by the bifunctional amine-active cross-linker [e.g. disuccinimidyl suberate (DSS)]. The model medicines of ginsenosides pre-activated by APTMS are further cross-linked with activated NPs, forming the desired nanomedicines (Nano-Fe-GSS). Sizes and structures of Fe@Fe₃O₄ NPs were characterized by transmission electron microscopy and X-ray diffraction, revealing that their core-shell structures consist of amorphous boron doped Fe cores and partial crystalline Fe₃O₄ shells. The accomplishment of coupling reactions in the final nanomedicines is confirmed by the characterization of the composition of NPs and Nano-Fe-GSS via X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FT-IR) spectroscopy. The nanoparticles’ effects as MRI contrast agents are further investigated by comparing the T₂ weighted spin echo imaging (T2WI) in livers before and after intravenous injection and intragastric administration of nanomedicines. The results indicate that these nanomedicines possess enhanced MRI effects. Investigation of the toxicity and metabolism of Nano-Fe-GSS suggests that they are safe to related vital organs. The results provide an efficient alternative route to synthesize desired multi-functional nanomedicines based on NPs and the active ingredients of Chinese herbs, which can promote their potential synergistic effects in anti-tumor therapy.     

Chitosan: A Unique Polysaccharide for Drug Delivery

Abstract

The aim of this review is to give an insight into the many potential applications of chitosan as a pharmaceutical drug carrier. The first part of this review concerns the principal uses of chitosan as an excipient in oral formulations (particularly as a direct tableting agent) and as a vehicle for parenteral drug delivery devices. The use of chitosan to manufacture sustained-release systems deliverable by other routes (nasal, ophthalmic, transdermal, and implantable devices) is discussed in the second part.     

Dendron-polymer hybrid mediated anticancer drug delivery for suppression of mammary cancer

Dendron-polymer-based nanoscale and stimuli-responsive drug delivery systems have shown great promise in tumor-targeting accumulation without significant toxicity.Here we report a dendronized polymer-doxorubicin(DOX)hybrid(DPDH)with an improved in vivo drug delivery efficiency for cancer therapy compared with a linear polymer-DOX conjugate(LPDC).The in vitro drug release profile of DOX indicates that DPDH displays pH-responsive drug release due to cleavage of hydrazone bonds since a greater amount of DOX is released at pH 5.2 at a faster rate than at pH 7.4.DPDH efficiently enters 4 T1 cells and releases DOX to induce cytotoxicity and apoptosis.Owing to the dendronzied structure,DPDH has a significantly longer blood circulation time than LPDC.DPDH substantially enhances the therapeutic efficacy to suppress tumor growth in a 4 T1 mammary cancer model than LPDC as well as free drug,evidenced from tumor growth inhibition,TUNEL assessment and histological analysis.Biosafety of DPDH is also confirmed from hemolysis,body weight shifts during treatment and pathological analysis.This study demonstrates the use of dendronized polymer-DOX hybrids for specific drug molecules is a promising approach for drug delivery.     

Hollow mesoporous silica nanoparticles as nanocarriers employed in cancer therapy: A review

Hollow mesoporous silica nanoparticles (HMSNs) have become an attractive drug carrier because of their unique characteristics including stable physicochemical properties, large specific surface area and facile functionalization, especially made into intelligent drug delivery systems (DDSs) for cancer therapy. HMSNs are employed to transport traditional anti-tumor drugs, which can solve the problems of drugs with instability, poor solubility and lack of recognition, etc., while significantly improving the anti-tumor effect. And an unexpected good result will be obtained by combining functional molecules and metal species with HMSNs for cancer diagnosis and treatment. Actually, HMSNs-based DDSs have developed relatively mature in recent years. This review briefly describes how to successfully prepare an ordinary HMSNs-based DDS, as well as its degradation, different stimuli-responses, targets and combination therapy. These versatile intelligent nanoparticles show great potential in clinical aspects.     

Plasmonic nanomaterials: A versatile phototheranostic platform of cancers

Phototheranostic platform emerges as a highly powerful tool against cancers due to unique features such as minimal invasiveness, high spatiotemporal resolution, and function integration. Plasmonic nanomaterials are able to achieve a myriad of diagnostic and therapeutic functionalities owing to their superior photophysical properties stemming from local surface plasmon resonance (LSPR), and enable them to act as a versatile phototheranostic platform. Therefore, a bridge is needed to link the underlying LSPR process and the plasmonic theranostic functionalities. To fill the gap, this review ventures to summarize the plasmonic nanomaterials-based phototheranostic modalities in mechanistic physics. Three major physical processes and the corresponding theranostic functionalities are outlined: (1) the excitation of LSPR arises significant field enhancement near the plasmonic nanomaterials, which can be harvested to magnify the output signal for fluorescence imaging, Raman scattering, and boost reactive oxygen species (ROS) production. (2) LSPR subsequently generates abundant hot carriers that are capable of catalyzing intracellular reactions and producing ROS, thereby fulfilling therapeutic purposes. (3) the LSPR finally decays either through heat or fluorescence, which indicates the plasmonic nanomaterials can either act as a heat source to trigger drug release, damage cellular component and delineate cancers, or enable visualizing tumor sites explicitly by fluorescence. This review hopes to give assistance on integration of these diagnostic and therapeutic functions by providing a big picture of the plasmonic nanomaterials-based nanomedicine. Finally, several limitations of current research in this regard are pointed out.     

In situ agar-carbomer hydrogel polycondensation: A chemical approach to regenerative medicine

Injectable hydrogels with in situ polycondensation capability are believed as powerful tools to be used in spinal cord injury (SCI) repair: they can be injected using minimally invasive techniques and can conform to any shape. Here, we finely tuned the chemistry of a promising hydrogel, specifically developed for cell and drug delivery purposes in SCI therapeutical strategies, in order to allow its injection through a 40 μm needle at solution state and to let gelation take place inside target tissue, just after injection. A solution was injected in vivo into a mouse spinal cord and consequent in situ gel formation was verified: magnetic resonance imaging showed presence of the polymeric network at injection site and histological analysis, coherently, revealed spherical enclosures in the spinal cord.This hydrogel showed to be a new biocompatible and microinvasive tool that can be used in vivo as a local reservoir for in situ delivery of drugs and cells. This paves the way for the future generation and in vivo experimental validation of new combined tissue engineering approaches.     

Synthesis of superparamagnetic CaCO3 mesocrystals for multistage delivery in cancer therapy

To develop a new system for site-specific targeting, superparamagnetic CaCO(3) mesocrystals with the properties of biocompatibility and biodegradability are designed and synthesized. They serve as carriers for the co-delivery of drug and gene nanoparticles via a multistage method for cancer therapy. With a porous structure, the mesocrystalline CaCO(3) particles encapsulate doxorubicin (DOX), Au-DNA, and Fe(3)O(4)@silica nanoparticles for magnetic control and therapy. As stage 1 microparticles (S1MPs), the nanoparticles-CaCO(3) system is designed to protect functional sections from degradation and phagocytosis in blood circulation. After the particle margination in vascular walls, the Au-DNA nanoparticles (stage 2 nanoparticles, S2NPs) and DOX are gradually released from S1MPs by degradation towards targeted tissues for biomedical therapy. The nanoparticles-CaCO(3) system exhibits high efficiency of intracellular delivery, especially in nuclear invasion. The successful expression of reporter gene and intracellular transport of DOX in vitro suggest potential as a co-delivery system for drug and gene therapy. In a mouse tumor model, the system with particle margination and two-step strategy affords the protection of functional nanoparticles and drug from clearance and inactivation by enzymes and proteins in vivo. The targeted delivery of S2NPs into tumors by this system is tenfold more efficient than that of the nanoparticles themselves. The drug is observed to be widely distributed in tumor slices. Thus, this platform exhibits an efficient approach in the targeted delivery of therapeutic nanoparticles and molecules via a multistage strategy, and can be used as a potential system in co-delivery of multiple agents for biomedical imaging and therapy.     

Peeling Back the Layers: Controlled Erosion and Triggered Disassembly of Multilayered Polyelectrolyte Thin Films

Methods for the layer‐by‐layer deposition of oppositely charged polymers on surfaces can be used to assemble thin multilayered films using a broad range of natural, synthetic, and biologically relevant materials. These methods also permit precise, nanometer‐scale control over the compositions and internal structures of multicomponent assemblies. Provided that the individual components of these materials are selected or designed appropriately, these methods provide tantalizing new opportunities to design thin films and coatings that provide spatial, temporal, or active control over the release of one or several different agents from surfaces. The last two years have seen a significant increase in reports describing the development of new chemical, physical, and biomolecular approaches to the controlled erosion, triggered disassembly, or general deconstruction of multilayered polymer films. In this Progress Report, we highlight recent work from our laboratory and several other groups toward the design of ultrathin multilayered assemblies that i) permit broad, tunable, and sophisticated control over film erosion, and ii) provide new opportunities for the localized release of macromolecular therapeutics, such as DNA and proteins, from surfaces.     

Monoolein: A Review of the Pharmaceutical Applications

Earlies studies suggest that solution calorimetry can be used to determine the extent of amorphous content of drug and excipient, when the solubility and dissolution rate of the compound in the chosen solvent are reasonably high. In the present study, the use of solution calorimetry for assessment of amorphous content of a sample that is not completely dissolved in a solvent was evaluated. Physical mixtures of lactose and spray‐dried lactose samples were analysed. The amorphous content of the physical mixtures and the spray‐dried samples varied from 0% to 100% determined by isothermal microcalorimetry. The enthalpy of solution (Δ_solH) was determined in water. The lactose samples were dissolved quickly in water. In addition, the enthalpy accompanied with an addition of a lactose sample in an over saturated aqueous solution (Δ_satH) (prepared from the corresponding lactose sample) was determined. The lactose sample did not completely dissolve in the over saturated aqueous solution. An excellent correlation was observed between Δ_solH and the amorphous content of the samples. Interestingly, there was a linear correlation also between Δ_satH and the amorphous content of the samples. Further, a linear relationship was observed between the Δ_satH and the Δ_solH of the samples. Therefore, solution calorimetry may represent a rapid and simple method for determining the amorphous content also in samples that are not completely dissolved in the solvent.     

Servitization of manufacturing in the new ICTs era: A survey on operations management

Servitization of manufacturing has become one of the main pathways for transition and upgrade in the manufacturing industry. New information and communication technologies (ICTs), such as the Internet of Things, Big Data, and Cloud Computing have enabled the servitization of manufacturing in terms of value creation, resource management, and supply chain management. This study presents a comprehensive review on the servitization in operations management in the era of new ICTs. A new value chain framework is proposed under the business model that revolves around servitization, which showcases the new activities and ways of implementation in the era of new ICTs. The virtualization, configuration, and evaluation of integrated manufacturing and service resources are analyzed. In particular, the methods used in new ICT-supported resource management platforms are surveyed. Problems in the supply chain management in manufacturing services (including the selection of partners, as well as the coordination, planning, and scheduling among members) are presented. This study concludes with a discussion on state-of-the-art servitization in operations management in the era of new ICTs.     

Structural effect and mechanism of C70-carboxyfullerenes as efficient sensitizers against cancer cells

Carboxyfullerenes with different adduct numbers and cage sizes are tested as photosensitizers for photodynamic therapy (PDT). The photodynamic efficiency of these carboxyfullerenes depends mainly on the cage size, C(60) versus C(70) , and to a lesser extent on the adduct numbers. In particular, malonic acid modified C(70) fullerenes are more efficient than their C(60) counterparts as photosensitizers, and the mechanism of cell death induced by C(70) -carboxyfullerene under light irradiation is investigated in detail. The results indicate that cell death occurs via necrosis accompanied by membrane blebbing, which is a unique phenomenon for photosensitizer-induced cell death. Since C(70) -carboxyfullerene displays an efficient PDT property and negligible dark cytotoxicity, it is promising for use in PDT applications, especially in vascular capillary diseases usually occurring under the surface.     

Methotrexate-conjugated L-lysine coated iron oxide magnetic nanoparticles for inhibition of MCF-7 breast cancer cells

Methotrexate (MTX), a stoichiometric inhibitor of dihydrofolate reductase enzyme, is a chemotherapeutic agent for treating a diversity of neoplasms. In this study, we design and developed a new formulation of MTX that serves as drug carrier and examined its cytotoxic effect in vitro. This target drug delivery system is dependent on the release of the MTX within the lysosomal compartment. The iron oxide magnetic nanoparticles (IONPs) were first surface-coated with L-lysine and subsequently conjugated with MTX through amidation between the carboxylic acid end groups on MTX and the amine groups on the IONPs surface. MTX-conjugated L-lysine coated IONPs (F-Lys-MTX NPs) was characterized by X-ray diffraction, thermogravimetric analysis, differential scanning calorimetry, Fourier transform infrared spectroscopy, vibrating sample magnetometer, and transmission electron microscopy techniques. The cytotoxicity of the void of MTX and F-Lys-MTX NPs were compared to each other by MTT assay of the treated MCF-7 cell lines. The results showed that the ζ-potential of F-Lys-MTX NPs was about ?5.49?mV and the average size was 43.72?±?4.73?nm. Model studies exhibited the release of MTX via peptide bond cleavage in the presence of proteinase K and at low pH. These studies specify that F-Lys-MTX NPs have a very remarkable anticancer effect, for breast cancer cell lines.     

Anticipating the effects of technological change: A new era of dynamics for human factors

Human factors studies the intersection between people, technology and work, with the major aim to find areas where design and working conditions produce human error. It relies on the knowledge base and research results of multiple fields of inquiry (ranging from computer science to anthropology) to do so. Technological change at this intersection (1) redefines the relationship between various players (both humans and machines), (2) transforms practice and shifts sources of error and excellence, and (3) often drives up operational requirements and pressures on operators. Human factors needs to predict these reverberations of technological change before a mature system has been built in order to steer design into the direction of cooperative human-machine architectures. The quickening tempo of technology change and the expansion of technological possibilities has largely converted the traditional shortcuts for access to a design process (task analysis, guidelines, verification and validation studies, etc.) into oversimplification fallacies that retard understanding, innovation, and, ultimately, human factors' credibility. There is an enormous need for the development of techniques that gain empirical access to the future-that generate human performance data about systems which have yet to be built.