Current Pharmaceutical Design - Volume 25, Issue 17, 2019

Articular cartilage is a connective tissue structure that is found in anatomical areas that are important for the movement of the human body. Osteoarthritis is the ailment that most often affects the articular cartilage. Due to its poor intrinsic healing capacity, damage to the articular cartilage is highly detrimental and at present the reconstructive options for its repair are limited. Tissue engineering and the science of nanobiomaterials are two lines of research that together can contribute to the restoration of damaged tissue. The science of nanobiomaterials focuses on the development of different nanoscale structures that can be used as carriers of drugs / cells to treat and repair damaged tissues such as articular cartilage. This review article is an overview of the composition of articular cartilage, the causes and treatments of osteoarthritis, with a special emphasis on nanomaterials as carriers of drugs and cells, which reduce inflammation, promote the activation of biochemical factors and ultimately contribute to the total restoration of articular cartilage.

Lysosomal Storage Disorders (LSDs), also known as lysosomal diseases (LDs) are a group of serious genetic diseases characterized by not only the accumulation of non-catabolized compounds in the lysosomes due to the deficiency of specific enzymes which usually eliminate these compounds, but also by trafficking, calcium changes and acidification. LDs mainly affect the central nervous system (CNS), which is difficult to reach for drugs and biological molecules due to the presence of the blood-brain barrier (BBB). While some therapies have proven highly effective in treating peripheral disorders in LD patients, they fail to overcome the BBB. Researchers have developed many strategies to circumvent this problem, for example, by creating carriers for enzyme delivery, which improve the enzyme’s half-life and the overexpression of receptors and transporters in the luminal or abluminal membranes of the BBB. This review aims to successfully examine the strategies developed during the last decade for the treatment of LDs, which mainly affect the CNS. Among the LD treatments, enzyme-replacement therapy (ERT) and gene therapy have proven effective, while nanoparticle, fusion protein, and small molecule-based therapies seem to offer considerable promise to treat the CNS pathology. This work also analyzed the challenges of the study to design new drug delivery systems for the effective treatment of LDs. Polymeric nanoparticles and liposomes are explored from their technological point of view and for the most relevant preclinical studies showing that they are excellent choices to protect active molecules and transport them through the BBB to target specific brain substrates for the treatment of LDs.

Macrophages play a role in almost every disease such as cancer, infections, injuries, metabolic and inflammatory diseases and are becoming an attractive therapeutic target. However, understanding macrophage diversity, tissue distribution and plasticity will help in defining precise targeting strategies and effective therapies. Active targeting of macrophages using nanoparticles for therapeutic purposes is still at its infancy but holds promises since macrophages have shown high specific uptake of nanoparticles. Here, we highlight recent progress in active nanotechnology-based systems gaining pivotal roles to target diverse macrophage subsets in diseased tissues.

Background: Tumours are no longer regarded as isolated masses of aberrantly proliferating epithelial cells. Rather, their properties depend on complex interactions between epithelial cancer cells and the surrounding stromal compartment within the tumour microenvironment. In particular, leukocyte infiltration plays a role in controlling tumour development and is now considered one of the hallmarks of cancer. Thus, in the last few years, immunotherapy has become a promising strategy to fight cancer, as its goal is to reprogram or activate antitumour immunity to kill tumour cells, without damaging the normal cells and provide long-lasting results where other therapies fail. However, the immune-related adverse events due to the low specificity in tumour cell targeting, strongly limit immunotherapy efficacy. In this regard, nanomedicine offers a platform for the delivery of different immunotherapeutic agents specifically to the tumour site, thus increasing efficacy and reducing toxicity. Indeed, playing with different material types, several nanoparticles can be formulated with different shape, charge, size and surface chemical modifications making them the most promising platform for biomedical applications. Aim: In this review, we will summarize the different types of cancer immunotherapy currently in clinical trials or already approved for cancer treatment. Then, we will focus on the most recent promising strategies to deliver immunotherapies directly to the tumour site using nanoparticles. Conclusion: Nanomedicine seems to be a promising approach to improve the efficacy of cancer immunotherapy. However, additional investigations are needed to minimize the variables in the production processes in order to make nanoparticles suitable for clinical use.

Increasing evidence has suggested that extracellular vesicles (EV) mediated bidirectional transfer of functional molecules (such as proteins, different types of RNA, and lipids) between cancer cells and tumor stromal cells (immune cells, endothelial cells, fibroblasts, stem cells) and strongly contributed to the reinforcement of cancer progression. Thus, intercellular EV-mediated signaling in tumor microenvironment (TME) is essential in the modulation of all processes that support and promote tumor development like immune suppression, angiogenesis, invasion and metastasis, and resistance of tumor cells to anticancer treatments. Besides EV potential to revolutionize our understanding of the cancer cell-stromal cells crosstalk in TME, their ability to selectively transfer different cargos to recipient cells has created excitement in the field of tumortargeted delivery of specific molecules for anticancer treatments. Therefore, in tight connection with previous findings, this review brought insight into the dual role of EV in modulation of TME. Thus, on one side EV create a favorable phenotype of tumor stromal cells for tumor progression; however, as a future new class of anticancer drug delivery systems EV could re-educate the TME to overcome main supportive processes for malignancy progression.

The combination of magnetism and upconversion luminescent property into one single nanostructure is fascinating for biological fields, such as multimodal bioimaging, targeted drug delivery, and imaging-guided therapy. In this review, we will provide the state-of-the-art advances on magnetic upconversion nanocomposites towards their bioapplications. Their structure design, synthesis methods, surface engineering and applications in bioimaging, drug delivery, therapy as well as biodetection will be covered.