Active nanotargeting is now one of the best approaches in many serious therapies such as cancer, inflammatory and gene disorders , with the advantage to specifically deliver active molecules to the target tissues or organs, improving the therapy efficiency and decreasing the exposure of patients to toxics. In this issue, we would highlight some of more recent and advanced strategies for active nanotargeting, also trying to focus on those pathologies for which the current and conventional treatments still exhibit limited efficacy and safety. Alterations into the articular cartilage lead to osteoarthritis, a severe joint disease only currently treated for symptoms or with surgery. The first review article [1] presents an overview of the composition, 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. In particular, locally administered nanobiomaterials such as hydrogels and nanohydrogels can promote in situ cartilage regeneration by in situ release cells, antiinflammatory drugs, and growth factors. Targeting brain is one of the most unsolved challenge in therapy. Biochemical studies more recently revealed the effects of Lysosomal storage disorders (LSDs), a group of serious genetic diseases characterized by the accumulation of non-catabolized compounds in the lysosomes. LDs mainly affect the central nervous systems (CNS), which is difficult to reach with drugs and biological molecules due to the presence of the blood-brain barrier (BBB). A review [2] aims to examine the strategies successfully developed during the last decade for the treatment of LDs. Among the LD treatments, this review also analyzed the challenges of the study to design new drug delivery systems for the effective treatment of the 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 [3]. In the last few years immunotherapy has become a promising strategy to fight cancer, as its goal is to reprogram or activate anti-tumour 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 [4]. 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. In particular, leukocyte infiltration plays a role in controlling tumour development and is now considered one of the hallmarks of cancer. 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. 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 tumor-targeted 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 future new class of anticancer drug delivery systems EV could re-educate the TME to overcome main supportive processes for malignancy progression [5]. Multifunctional nanocomposites have a controlled drug release property [6]. Interestingly, the up‐conversion emission intensity of the multifunctional carrier increases with the released amount of model drug, thus allowing the release process to be monitored and tracked by the change of photoluminescence intensity. This composite can act as a multifunctional drug carrier system, which can realize the targeting and monitoring of drugs simultaneously. 1. “Targeting Polymeric Nanobiomaterials as a Platform for Cartilage Tissue Engineering”. 2. “New Advanced Strategies for the Treatment of Lysosomal Diseases Affecting the Central Nervous System”. 3. “Active targeting of macrophages”. 4. “Nanoparticles: properties and applications in cancer immunotherapy”. 5. “Intercellular Crosstalk via Extracellular Vesicles in Tumor Milieu as Emerging Therapies for Cancer Progression”. 6. “Recent Advances in Magnetic Upconversion Nanocomposites for Bioapplications”

Active nanotargeting in medicine

Di Martino P.
2019-01-01

Abstract

Active nanotargeting is now one of the best approaches in many serious therapies such as cancer, inflammatory and gene disorders , with the advantage to specifically deliver active molecules to the target tissues or organs, improving the therapy efficiency and decreasing the exposure of patients to toxics. In this issue, we would highlight some of more recent and advanced strategies for active nanotargeting, also trying to focus on those pathologies for which the current and conventional treatments still exhibit limited efficacy and safety. Alterations into the articular cartilage lead to osteoarthritis, a severe joint disease only currently treated for symptoms or with surgery. The first review article [1] presents an overview of the composition, 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. In particular, locally administered nanobiomaterials such as hydrogels and nanohydrogels can promote in situ cartilage regeneration by in situ release cells, antiinflammatory drugs, and growth factors. Targeting brain is one of the most unsolved challenge in therapy. Biochemical studies more recently revealed the effects of Lysosomal storage disorders (LSDs), a group of serious genetic diseases characterized by the accumulation of non-catabolized compounds in the lysosomes. LDs mainly affect the central nervous systems (CNS), which is difficult to reach with drugs and biological molecules due to the presence of the blood-brain barrier (BBB). A review [2] aims to examine the strategies successfully developed during the last decade for the treatment of LDs. Among the LD treatments, this review also analyzed the challenges of the study to design new drug delivery systems for the effective treatment of the 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 [3]. In the last few years immunotherapy has become a promising strategy to fight cancer, as its goal is to reprogram or activate anti-tumour 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 [4]. 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. In particular, leukocyte infiltration plays a role in controlling tumour development and is now considered one of the hallmarks of cancer. 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. 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 tumor-targeted 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 future new class of anticancer drug delivery systems EV could re-educate the TME to overcome main supportive processes for malignancy progression [5]. Multifunctional nanocomposites have a controlled drug release property [6]. Interestingly, the up‐conversion emission intensity of the multifunctional carrier increases with the released amount of model drug, thus allowing the release process to be monitored and tracked by the change of photoluminescence intensity. This composite can act as a multifunctional drug carrier system, which can realize the targeting and monitoring of drugs simultaneously. 1. “Targeting Polymeric Nanobiomaterials as a Platform for Cartilage Tissue Engineering”. 2. “New Advanced Strategies for the Treatment of Lysosomal Diseases Affecting the Central Nervous System”. 3. “Active targeting of macrophages”. 4. “Nanoparticles: properties and applications in cancer immunotherapy”. 5. “Intercellular Crosstalk via Extracellular Vesicles in Tumor Milieu as Emerging Therapies for Cancer Progression”. 6. “Recent Advances in Magnetic Upconversion Nanocomposites for Bioapplications”
2019
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Current Pharmaceutical Design, 2019 Volume 25 issue 17 pp. 1913-1914.pdf

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