Nanomedicine and nano delivery systems are a relatively new but rapidly developing science where materials in the nanoscale range are employed to serve as means of diagnostic tools or to deliver therapeutic agents to specific targeted sites in a controlled manner. Nanotechnology offers multiple benefits in treating chronic human diseases by site-specific, and target-oriented delivery of precise medicines. Recently, there are a number of outstanding applications of the nanomedicine (chemotherapeutic agents, biological agents, immunotherapeutic agents etc.) in the treatment of various diseases. The current review, presents an updated summary of recent advances in the field of nanomedicines and nano based drug delivery systems through comprehensive scrutiny of the discovery and application of nanomaterials in improving both the efficacy of novel and old drugs (e.g., natural products) and selective diagnosis through disease marker molecules. The opportunities and challenges of nanomedicines in drug delivery from synthetic/natural sources to their clinical applications are also discussed. In addition, we have included information regarding the trends and perspectives in nanomedicine area.
Methotrexate (MTX), an anti-neoplastic agent used for breast cancer treatment, has restricted clinical applications due to poor water solubility, non-specific targeting and adverse side effects. To overcome these limitations, MTX was co-encapsulated with an active-targeting platform known as superparamagnetic iron oxide nanoparticles (SPIONs) in a lipid-based homing system, nanostructured lipid carrier (NLC). This multi-modal therapeutic regime was successfully formulated with good colloidal stability, bio- and hemo-compatibility. MTX-SPIONs co-loaded NLC was time-dependent cytotoxic towards MDA-MB-231 breast cancer cell line with IC50 values of 137 μg/mL and 12 μg/mL at 48 and 72 h, respectively. The MTX-SPIONs co-loaded NLC was internalized in the MDA-MB-231 cells via caveolae-mediated endocytosis in a time-dependent manner, and the superparamagnetic properties were sufficient to induce, under a magnetic field, a localized temperature increase at cellular level resulting in apoptotic cell death. In conclusion, MTX-SPIONs co-loaded NLC is a potential magnetic guiding multi-modal therapeutic system for the treatment of breast cancer.
From the time when Roentgen and other physicists made the discoveries which led to the development of radiology, radiotherapy and nuclear medicine, medical physicists have played a pivotal role in the development of new technologies that have revolutionized the way medicine is practiced today. Medical physicists have been transforming scientific advances in the research laboratories to improving the quality of life for patients; indeed innovations such as computed tomography, positron emission tomography and linear accelerators which collectively have improved the medical outcomes for millions of people. In order for radiation-delivery techniques to improve in targeting accuracy, optimal dose distribution and clinical outcome, convergence of imaging and therapy is the key. It is timely for these two specialties to work closer again. This can be achieved by means of cross-disciplinary research, common conferences and workshops, and collaboration in education and training for all. The current emphasis is on enhancing the specific skill development and competency of a medical physicist at the expense of their future roles and opportunities. This emphasis is largely driven by financial and political pressures for optimizing limited resources in health care. This has raised serious concern on the ability of the next generation of medical physicists to respond to new technologies. In addition in the background loom changes of tsunami proportion. The clearly defined boundaries between the different disciplines in medicine are increasingly blurred and those between diagnosis, therapy and management are also following suit. The use of radioactive particles to treat tumours using catheters, high-intensity focused ultrasound, electromagnetic wave ablation and photodynamic therapy are just some areas challenging the old paradigm. The uncertainty and turf battles will only explode further and medical physicists will not be spared. How would medical physicists fit into this changing scenario? We are in the midst of molecular revolution. Are we prepared to explore the newer technologies such as nanotechnology, drug discovery, pre-clinical imaging, optical imaging and biomedical informatics? How are our curricula adapting to the changing needs? We should remember the late Professor John Cameron who advocated imagination and creativity - these important attributes will make us still relevant in 2020 and beyond. To me the future is clear: "To achieve more, we should imagine together."
Graphene and its derivative materials present high potential towards medical and biological applications, including drug delivery and bioimaging, due to their exceptional properties such as thermal conductivity and high specific surface area. The main focus of this work is to review the current development of graphene materials and the derivatives for biocompatible, bioimaging and drug delivery applications. Also, the synthesis methods with variation of graphene nanocomposites and the functionalisation will be further explained. For the graphene approaches, chemical vapour deposition (CVD) is the best-known technique to make high-quality graphene sheet by growth route with mass production. By considering the organic graphene nanocomposites, the biocompatibility and cytotoxic effects against graphene nanocomposites were evaluated for biomedical employments such as high quality bioimaging and effective drug delivery for cancer treatments. For example, graphene oxide incorporated with PEG and loaded with SN 38 for camptothecin analolgue as anticancer drug and revealed high cytotoxicity has an effect of 1000 times better effect than CPT in HCT-116 cells. Their drug delivery ability for both in-vivo and in-vitro applications compared to the controlled drugs such as doxorubicin (DOX) will be discussed accordingly. The graphene and its deriavatives possess some intriguing properties, which will lead to drug delivery due to strong biocompatibility and cyctotoxic effect towards biomedicine applications.
Nanotechnology has gained significant interest from biomedical and analytical researchers in recent years. Carbon dots (C-dots), a new member of the carbon nanomaterial family, are spherical, nontoxic, biocompatible, and discrete particles less than 10nm in diameter. Research interest has focused on C-dots because of their ultra-compact nanosize, favorable biocompatibility, outstanding photoluminescence, superior electron transfer ability, and versatile surface engineering properties. C-dots show significant potential for use in cellular imaging, biosensing, targeted drug delivery, and other biomedical applications. Here we discuss C-dots, in terms of their physicochemical properties, fabrication techniques, toxicity issues, surface engineering and biomedical potential in drug delivery, targeting as well as bioimaging.
Protistan parasitic infections contribute significantly to morbidity and mortality, causing more than 2 billion human infections annually. However, current treatments are often limited; due to ineffective drugs and drug resistance, thus better options are urgently required. In the present context, theranostics agents are those that offer simultaneous detection, diagnosis and even treatment of protistan parasitic diseases. "Nanotheranostics" is the term used to describe such agents, that are around 100 nm or less in size. Anti-parasitic activity of nanoparticles (NPs) has been reported, and many have useful intrinsic imaging properties, but it is perhaps their multifunctional nature that offers the greatest potential. NPs may be used as adapters onto which various subunits with different functions may be attached. These subunits may facilitate targeting parasites, coupled with toxins to eradicate parasites, and probe subunits for detection of particles and/or parasites. The modular nature of nano-platforms promises a "mix and match" approach for the construction of tailored agents by using combinations of these subunits against different protistan parasites. Even though many of the subunits have shown promise alone, these have not yet been put together convincingly enough to form working theranostics against protistan parasites. Although the clinical application of nanotheranostics to protistan parasitic infections in humans requires more research, we conclude that they offer not just a realisation of Paul Ehrlich's long imagined "magic bullet" concept, but potentially are magic bullets combined with tracer bullets.
Neurodegenerative disorder is an illness involving neural dysfunction/death attributed to complex pathological processes, which eventually lead to the mortality of the host. It is generally recognized through features such as mitochondrial dysfunction, protein aggregation, oxidative stress, metal ions dyshomeostasis, membrane potential change, neuroinflammation and neurotransmitter impairment. The aforementioned neuronal dysregulations result in the formation of a complex neurodegenerative microenvironment (NME), and may interact with each other, hindering the performance of therapeutics for neurodegenerative disease (ND). Recently, smart nanoassemblies prepared from functional nanoparticles, which possess the ability to interfere with different NME factors, have shown great promise to enhance the diagnostic and therapeutic efficacy of NDs. Herein, this review highlights the recent advances of stimuli-responsive nanoassemblies that can effectively combat the NME for the management of ND. The first section outlined the NME properties and their interrelations that are exploitable for nanoscale targeting. The discussion is then extended to the controlled assembly of functional nanoparticles for the construction of stimuli-responsive nanoassemblies. Further, the applications of stimuli-responsive nanoassemblies for the enhanced diagnosis and therapy of ND are introduced. Finally, perspectives on the future development of NME-tailored nanomedicines are given.
Three-dimensional assembly of graphene hydrogel is rapidly attracting the interest of researchers because of its wide range of applications in energy storage, electronics, electrochemistry, and waste water treatment. Information on the use of graphene hydrogel for biological purposes is lacking, so we conducted a preliminary study to determine the suitability of graphene hydrogel as a substrate for cell growth, which could potentially be used as building blocks for biomolecules and tissue engineering applications.
Breast cancer is the most common malignancy worldwide, especially among women, with substantial after-treatment effects. The survival rates of breast cancer have decreased over the years even with the existence of various therapeutic strategies, specifically, chemotherapy. Clinical drugs administered for breast cancer appear to be non-targeting to specific cancer sites leading to severe side effects and potentially harming healthy cells instead of just killing cancer cells. This leads to the need for designing a targeted drug delivery system. Nanomaterials, both organic and inorganic, are potential drug nanocarriers with the ability of targeting, imaging and tracking. Various types of nanomaterials have been actively researched together with their drug conjugate. In this review, we focus on selected nanomaterials, namely solid-lipid, liposomal, polymeric, magnetic nanoparticles, quantum dots, and carbon nanotubes and their drug conjugates, for breast cancer studies. Their advantages, disadvantages and previously conducted studies were highlighted.
A facile electrochemical sandwich immunosensor for the detection of a breast cancer biomarker, the human epidermal growth factor receptor 2 (HER2), was designed, using lead sulfide quantum dots-conjugated secondary HER2 antibody (Ab2-PbS QDs) as a label. Using Ab2-PbS QDs in the development of electrochemical immunoassays leads to many advantages such as straightforward synthesis and well-defined stripping signal of Pb(II) through acid dissolution, which in turn yields better sensing performance for the sandwiched immunosensor. In the bioconjugation of PbS QDs, the available amine and hydroxyl groups from secondary anti-HER2 and capped PbS QDs were bound covalently together via carbonyldiimidazole (CDI) acting as a linker. In order to quantify the biomarker, SWV signal was obtained, where the Pb2+ ions after acid dissolution in HCl was detected. The plated mercury film SPCE was also detected in situ. Under optimal conditions, HER2 was detected in a linear range from 1-100 ng/mL with a limit of detection of 0.28 ng/mL. The measures of satisfactory recoveries were 91.3% to 104.3% for the spiked samples, displaying high selectivity. Therefore, this method can be applied to determine HER2 in human serum.
Age-related macular degeneration (AMD), a degenerative eye disease, is the major cause of irreversible loss of vision among individuals aged 50 and older. Both genetic and environmental factors are responsible for the progressive damage to central vision. It is a multifactorial retinal disease with features such as drusen, hypopigmentation and/or hyperpigmentation of the retinal pigment epithelium, and even choroidal neovascularization in certain patients. AMD is of two major forms: exudative (wet) and atrophic (dry) with changes affecting the macula leading to impaired vision. Although the retina remains an accessible portion for delivering drugs, there are no current options to cure or treat AMD. The existing expensive therapeutics are unable to treat the underlying pathology but display several side effects. However, recent innovations in nanotherapeutics provide an optimal alternative of drug delivery to treat the neovascular condition. These new-age technologies in the nanometer scale would enhance bioactivity and improve the bioavailability of drugs at the site of action to treat AMD. The nanomedicine also provides sustained release of the drug with prolonged retention after penetrating across the ocular tissues. In this review, the insights into the cellular and molecular mechanisms associated with the pathophysiology of AMD are provided. It also serves to review the current progress in nanoparticle-based drug delivery systems that offer feasible treatments in AMD.
186gRe (T1/2 = 3.7183 d, E(β-)mean = 346.7 keV, I(β-)mean = 92.59%), a mixed beta and γ-emitter shows great potential for use in theranostic applications. The dominant 185Re(n,γ) route, via use of a nuclear reactor, provides 186gRe in carrier added form with low specific activity, while cyclotrons offer no carrier-added (NCA) high specific activity production of 186gRe. However, to be able to select the best possible nuclear reaction and to optimize the production route via the use of a cyclotron, information on the excitation function for the reaction of interest as well as for the competing reactions is necessary. Accordingly, we have conducted a detailed study of the excitation functions for natW(d, x) reactions in seeking optimized parameters for the NCA production of 186gRe. Noting a discrepancy among the experimental data, we made an evaluation of the available literature, finally selecting optimum parameters for the production of 186gRe via the 186W(d,2n)186Re reaction. These beam parameters were then used for batch production of 186gRe by irradiating an enriched 186W metallic powder target, followed by a subsequent automated chemical separation process. The preliminary results show 98.1% radionuclidic purity of 186gRe at 8 h subsequent to the End of Bombardment (EOB), offering the potential for use in clinical applications.
Highly controllable dendritic structural design means dendrimers are a leading carrier in drug delivery applications. Dendrimer- and other nanocarrier-based hybrid systems are an emerging platform in the field of drug delivery. This review is a compilation of increasing reports of dendrimer interactions, such as dendrimer-liposome, dendrimer-carbon-nanotube, among others, known as hybrid carriers. This should prompt entirely new research with promising results for these hybrid carriers. It is assumed that such emerging hybrid nanosystems - from combining two already-established drug delivery platforms - could lead the way for the development of newer delivery systems with multiple applicability for latent theranostic applications in the future.
The reported work demonstrates and discusses the effect of supercritical fluid density (pressure and temperature of supercritical fluid carbon dioxide) on particle size and distribution using the supercritical antisolvent (SAS) method in the purpose of drug encapsulation. In this study, paracetamol was encapsulated inside L-polylactic acid, a semicrystalline polymer, with different process parameters, including pressure and temperature, using the SAS process. The morphology and particle size of the prepared nanoparticles were determined by scanning electron microscopy and transmission electron microscopy. The results revealed that increasing temperature enhanced mean particle size due to the plasticizing effect. Furthermore, increasing pressure enhanced molecular interaction and solubility; thus, particle size was reduced. Transmission electron microscopy images defined the internal structure of nanoparticles. Thermal characteristics of nanoparticles were also investigated via differential scanning calorimetry. Furthermore, X-ray diffraction pattern revealed the changes in crystallinity structure during the SAS process. In vitro drug release analysis determined the sustained release of paracetamol in over 4 weeks.
Neuroregeneration is the regrowth or repair of nervous tissues, cells, or cell products involved in neurodegeneration and inflammatory diseases of the nervous system like Alzheimer's disease and Parkinson's disease. Nowadays, application of nanotechnology is commonly used in developing nanomedicines to advance pharmacokinetics and drug delivery exclusively for central nervous system pathologies. In addition, nanomedical advances are leading to therapies that disrupt disarranged protein aggregation in the central nervous system, deliver functional neuroprotective growth factors, and change the oxidative stress and excitotoxicity of affected neural tissues to regenerate the damaged neurons. Carbon nanotubes and graphene are allotropes of carbon that have been exploited by researchers because of their excellent physical properties and their ability to interface with neurons and neuronal circuits. This review describes the role of carbon nanotubes and graphene in neuroregeneration. In the future, it is hoped that the benefits of nanotechnologies will outweigh their risks, and that the next decade will present huge scope for developing and delivering technologies in the field of neuroscience.
The number of cancer cases worldwide in terms of morbidity and mortality is a serious concern, despite the presence of therapeutic interventions and supportive care. Limitations in the current available diagnosis methods and treatments methods may contribute to the increase in cancer mortality. Theranostics, is a novel approach that has opened avenues for the simultaneous precise diagnosis and treatment for cancer patients. Although still in the early development stage, theranostic agents such as quantum dots, radioisotopes, liposomes and plasmonic nanobubbles can be bound to anticancer drugs, cancer cell markers and imaging agents, with the support of available imaging techniques, provide the potential to facilitate diagnosis, treatment and management of cancer patients. Herein, we discuss the potential benefits of several theranostic tools for the management of cancer. Specifically, quantum dots, radio-labelled isotopes, liposomes and plasmonic nanobubbles coupled with targeting agents and/or anticancer molecules and imaging agents as theranostic agents are deliberated upon in this review. Overall, the use of theranostic agents shows promise in cancer management. Nevertheless, intensive research is required to realize these expectations.
Diabetes mellitus has been a threat to humans for many years. Amongst the different diabetes types, type 2 diabetes mellitus is the most common, and this is due to drastic changes in human lifestyle such as lack of exercise, stressful life and so on. There are a large number of conventional treatment methods available for type 2 diabetes mellitus. However, most of these methods are curative and are only applicable when the patient is highly symptomatic. Effective treatment strategies should be geared towards interfering with cellular and bio molecular mechanisms associated with the development and sustenance of the disease. In recent years, research into the medical potential of nanoparticles has been a major endeavor within the pharmaceutical industries. Nanoparticles display unique and tuneable biophysical characteristics which are determined by their shape and size. Nanoparticles have been used to manifest the properties of drugs, and as carriers for drug and vaccine delivery. Notwithstanding, there are further opportunities for nanoparticles to augment the treatment of a wide range of life threatening diseases that are yet to be explored. This review article seeks to highlight the application of potential nano-formulations in the treatment of type 2 diabetes mellitus. In addition, the activity of nanomedicine supplements in reversing insulin resistance is also discussed.
A microring resonator (MRRs) system incorporated with a add/drop filter is proposed in which ultra-short single, multi-temporal, and spatial optical soliton pulses are simulated and used to kill abnormal cells, tumors, and cancer. Chaotic signals are generated by a bright soliton pulse within a nonlinear MRRs system. Gold nanoparticles and ultra-short femtosecond/picosecond laser pulses' interaction holds great interest in laser nanomedicine. By using appropriate soliton input power and MRRs parameters, desired spatial and temporal signals can be generated over the spectrum. Results show that short temporal and spatial solitons pulse with FWHM = 712 fs and FWHM = 17.5 pm could be generated. The add/drop filter system is used to generate the high-capacity, ultra-short soliton pulses in the range of nanometer/second and picometer/second.