Current Pharmaceutical Design - Volume 25, Issue 13, 2019

Cancer vaccines have been widely explored as a key tool for effective cancer immunotherapy. Despite a convincing rationale behind cancer vaccines, extensive past efforts were unsuccessful in mediating significantly relevant anti-tumor activity in clinical studies. One of the major reasons for such poor outcome, among others, is the low immunogenicity of more traditional vaccines, such as peptide-, protein- and DNA- based vaccines. Recently, mRNA emerged as a promising alternative to traditional vaccine strategies due to its high immunogenicity, suitability for large-scale and low-cost production, and superior safety profile. However, the clinical application of mRNA-based anti-cancer vaccines has been limited by their instability and inefficient in vivo delivery. Recent technological advances have now largely overcome these issues and lipid-based vectors have demonstrated encouraging results as mRNA vaccine platforms against several types of cancers. This review intends to provide a detailed overview of lipid-based vectors for the development of therapeutic mRNA-based anti-tumor vaccines.

Quantum dots (QDs) have received much attention due to their extraordinary optical application in medical diagnostics, optoelectronics and in energy storage devices. The most conventional QDs are based on semiconductors that comprise heavy metals whose applications are limited due to toxicity and potential environmental hazard. Of late, researchers are focusing on carbon-based quantum dots, which have recently emerged as a new family of zero-dimensional nanostructured materials. They are spherical in shape with a size below 10 nm and exhibit excitation-wavelength-dependent photoluminescence (PL). Carbon quantum dots (CQDs) have unique optical, photoluminescence and electrochemical properties. They are environment-friendly with low toxicity as compared to toxic heavy metal quantum dots. Generally, CQDs are derived from chemical precursor materials, but recently researchers have focused their attention on the production of CQDs from waste biomass materials due to the economic and environmental exigency. In this review, recent advances in the synthesis of CQDs from waste biomass materials, functionalization and modulation of CQDs and their potential application of biosensing are focused. This review also brings out some challenges and future perspectives for developing smart biosensing gadgets based on CQDs.

The current strategies to treat different kinds of cancer are mainly based on chemotherapy, surgery and radiation therapy. Unfortunately, these approaches are not specific and rather invasive as well. In this scenario, metal nano-shells, in particular gold-based nanoshells, offer interesting perspectives in the effort to counteract tumor cells, due to their unique ability to tune Surface Plasmon Resonance in different light-absorbing ranges. In particular, the Visible and Near Infrared Regions of the electromagnetic spectrum are able to penetrate through tissues. In this way, the light absorbed by the gold nanoshell at a specific wavelength is converted into heat, inducing photothermal ablation in treated cancer cells. Furthermore, inert gold shells can be easily functionalized with different types of molecules in order to bind cellular targets in a selective manner. This review summarizes the current state-of-art of nanosystems embodying gold shells, regarding methods of synthesis, bio-conjugations, bio-distribution, imaging and photothermal effects (in vitro and in vivo), providing new insights for the development of multifunctional antitumor drugs.

MNPs find numerous important biomedical applications owing to their high biocompatibility and unique magnetic properties at the bottom level. Among several other biomedical applications, MNPs are gaining importance in treating various kinds of cancer either as a hyperthermia agent alone or as a drug/gene carrier for single or combined therapies. At the same time, another type of nano-carrier with lipid bilayer, i.e. liposomes, has also emerged as a platform for administration of pharmaceutical drugs, which sees increasing importance as a drug/gene carrier in cancer therapy due to its excellent biocompatibility, tunable particle size and the possibility for surface modification to overcome biological barriers and to reach targeted sites. MLs that combine MNPs with liposomes are endowed with advantages of both MNPs and liposomes and are gaining importance for cancer therapy in various modes. Hence, we will start by reviewing the synthesis methods of MNPs and MLs, followed by a comprehensive assessment of current strategies to apply MLs for different types of cancer treatments. These will include thermo-chemotherapy using MLs as a triggered releasing agent to deliver drugs/genes, photothermal/ photodynamic therapy and combined imaging and cancer therapy.

Cancer-related mortality is a leading cause of death among both men and women around the world. Target-specific therapeutic drugs, early diagnosis, and treatment are crucial to reducing the mortality rate. One of the recent trends in modern medicine is “Theranostics,” a combination of therapeutics and diagnosis. Extensive interest in magnetic nanoparticles (MNPs) and ultrasmall superparamagnetic iron oxide nanoparticles (NPs) has been increasing due to their biocompatibility, superparamagnetism, less-toxicity, enhanced programmed cell death, and auto-phagocytosis on cancer cells. MNPs act as a multifunctional, noninvasive, ligand conjugated nano-imaging vehicle in targeted drug delivery and diagnosis. In this review, we primarily discuss the significance of the crystal structure, magnetic properties, and the most common method for synthesis of the smaller sized MNPs and their limitations. Next, the recent applications of MNPs in cancer therapy and theranostics are discussed, with certain preclinical and clinical experiments. The focus is on implementation and understanding of the mechanism of action of MNPs in cancer therapy through passive and active targeting drug delivery (magnetic drug targeting and targeting ligand conjugated MNPs). In addition, the theranostic application of MNPs with a dual and multimodal imaging system for early diagnosis and treatment of various cancer types including breast, cervical, glioblastoma, and lung cancer is reviewed. In the near future, the theranostic potential of MNPs with multimodality imaging techniques may enhance the acuity of personalized medicine in the diagnosis and treatment of individual patients.

Drug discovery is generally considered as a costly affair and it takes approximately 15 years to reach a new chemical entity into the market. Among the recent potent drug molecules with most effective pharmacological properties, very few reached for Phase I clinical trial in humans. Unfortunately, the historical average reveals an almost 90% overall attrition rate in clinical trials. The solubility and permeability of a drug are the critical factors influencing the success of a drug. Oral drug delivery systems still continue to exist as the most favored, simplest and easiest administration route. A huge number of potential clinical candidates won’t make it to the market or accomplish their maximum capacity except if their solubility and oral bioavailability are enhanced by formulation. The solubility of drugs will continue to exist as important aspects of formulation development. With the emergence of synthetic methods for new molecule synthesis in chemistry and better screening methods, the number of poorly water soluble compounds has dramatically expanded in the last few years. Solid dispersion is one of the most important techniques as it can be prepared by several methods. It is mostly prepared with a drug having poor water solubility and it explores hydrophilic polymers either individually or in combination for the enhancement of solubility. In comparison to the conventional formulations such as tablets or capsules, there are different methods with which solid dispersions can be prepared and also have many benefits over conventional drug delivery approaches. Solid dispersion systems are potential for increasing the solubility, oral absorption and bioavailability of drugs and the significance of the solid dispersion technology is constantly increasing. The main focus of this review is to present recent advancements in the area of solid dispersion. This review also includes an account of recent patents on solid dispersion and clinical status of solid dispersion based formulations.

Nanoscience becomes one of the most cutting-edge research directions in recent years since it is gradually matured from basic to applied science. Nanoparticles (NPs) and nanomaterials (NMs) play important roles in various aspects of biomedicine science, and their influences on the environment have caused a whole range of uncertainties which require extensive attention. Due to the quantitative and dynamic information provided for human proteome, mass spectrometry (MS)-based quantitative proteomic technique has been a powerful tool for nanomedicine study. In this article, recent trends of progress and development in the nanomedicine of proteomics were discussed from quantification techniques and publicly available resources or tools. First, a variety of popular protein quantification techniques including labeling and label-free strategies applied to nanomedicine studies are overviewed and systematically discussed. Then, numerous protein profiling tools for data processing and postbiological statistical analysis and publicly available data repositories for providing enrichment MS raw data information sources are also discussed.

Background: Mycobacterium group contains several pathogenic bacteria including M. tuberculosis where the emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) is alarming for human and animal health around the world. The condition has further aggravated due to the speed of discovery of the newer drugs has been outpaced by the rate of resistance developed in microorganisms, thus requiring alternative combat strategies. For this purpose, nano-antimicrobials have emerged as a potential option. Objective: The current review is focused on providing a detailed account of nanocarriers like liposome, micelles, dendrimers, solid lipid NPs, niosomes, polymeric nanoparticles, nano-suspensions, nano-emulsion, mesoporous silica and alginate-based drug delivery systems along with the recent updates on developments regarding nanoparticle-based therapeutics, vaccines and diagnostic methods developed or under pipeline with their potential benefits and limitations to combat mycobacterial diseases for their successful eradication from the world in future. Results: Distinct morphology and the underlying mechanism of pathogenesis and resistance development in this group of organisms urge improved and novel methods for the early and efficient diagnosis, treatment and vaccination to eradicate the disease. Recent developments in nanotechnology have the potential to meet both the aspects: nano-materials are proven components of several efficient targeted drug delivery systems and the typical physicochemical properties of several nano-formulations have shown to possess distinct bacteriocidal properties. Along with the therapeutic aspects, nano-vaccines and theranostic applications of nano-formulations have grown in popularity in recent times as an effective alternative means to combat different microbial superbugs. Conclusion: Nanomedicine holds a bright prospect to perform a key role in global tuberculosis elimination program.