Smart Nanoparticle-based Platforms for Regulating Tumor Microenvironment and Cancer Immunotherapy

The tumor development and metastasis are closely related to the tumor microenvironment (TME). Recently, several studies have indicated that modulating TME could enhance cancer immunotherapy. Among various approaches to modulating TME, nanoparticles (NPs) with unique inherent advantages and smart modified characteristics are promising candidates in delivering drugs to cancer cells, amplifying the therapeutic effects, and leading to a cascade of immune responses. In this review, we briefly introduce several smart NP-based platforms, such as responsive NPs, targeting NPs, and the composition of TME, including dendritic cells, macrophages, fibroblasts, endothelial cells, myeloid-derived suppressor cells, and regulatory T cells. Moreover, the recent applications of smart NP-based platforms in regulating TME and cancer immunotherapy are briefly introduced. Finally, we discuss the advantages and disadvantages of these smart NP-based platforms in potential clinical translation

Copper-Free Click Chemistry Modification of Nanovectors For Integrin Targeted Cancer Therapy (Book Chapter)

Strain-promoted azide-alkyne cycloaddition (SPAAC) click chemistry is the chemical reaction between azide and cyclooctyne groups. This reaction can conjugate biological molecules, such as peptides, in a highly selective way under mild conditions without cross-reaction with the most widely existing reactive groups, such as amine, carboxylic acid, and hydroxide. Thus, the SPAAC reaction is very versatile for biomolecules conjugation. In this book chapter, we provide detailed protocols of conjugation of integrin targeting peptides to either amine or carboxylic acid terminated porous silicon nanovectors by SPAAC, which can be used to enhance the cellular uptake for intracellular cancer drug delivery and for in vivo cancer theranostics.Peer reviewe

Nanomedicines to tackle myocardial infarction: where are we now and where are we going?

Cardiovascular diseases (CVD) are responsible for the highest mortality rates globally. About one-third of the CVD-related casualties derive from ischemic heart diseases, which cause an irreversible injury to the myocardium. As a result of the very limited capacity of the heart tissue to recover from the ischemic insult, this usually leads to remodeling and scarring of the cardiac tissue, eventually progressing to irreversible heart failure. Currently, there is no major discovery of an effective cure to restore the function of an injured heart. Therefore, there is an unmet need to find a permanent solution for patients suffering from ischemic heart disease (IHD) and heart failure. In this regard, nanoparticles made of biomaterials called the attention of the scientific community as potential platform to deliver different therapeutics to the injured heart. Particulate nanomedicines, currently at the pre-clinical stage, are arising as a promising tool to provide minimally invasive treatment, an important aspect to take into account for clinical translation and patient compliance, and specifically deliver therapeutics to the injured myocardium. Here, we discuss about the current knowledge on the nanomedicines investigated for myocardial infarction, and how we see they can help and support medical doctors in shaping the future of IHD treatments.Peer reviewe

Selenium Nanoparticles for Biomedical Applications: From Development and Characterization to Therapeutics

Selenium (Se) is an essential element to human health that can be obtained in nature through several sources. In the human body, it is incorporated into selenocysteine, an amino acid used to synthesize several selenoproteins, which have an active center usually dependent on the presence of Se. Although Se shows several beneficial properties in human health, it has also a narrow therapeutic window, and therefore the excessive intake of inorganic and organic Se-based compounds often leads to toxicity. Nanoparticles based on Se (SeNPs) are less toxic than inorganic and organic Se. They are both biocompatible and capable of effectively delivering combinations of payloads to specific cells following their functionalization with active targeting ligands. Herein, the main origin of Se intake, its role on the human body, and its primary biomedical applications are revised. Particular focus will be given to the main therapeutic targets that are explored for SeNPs in cancer therapies, discussing the different functionalization methodologies used to improve SeNPs stability, while enabling the extensive delivery of drug-loaded SeNP to tumor sites, thus avoiding off-target effects.Peer reviewe

Recent advances in Fenton and Fenton-like reaction mediated nanoparticle in cancer therapy

Fenton and Fenton like reaction have been well clarified as efficient reactive oxygen species (ROS) sources in tumor, and have been widely developed into a cancer treatment method. Meanwhile, transition metal-based nanomaterials with Fenton or Fenton like reaction characteristics also have been well explored as therapeutic agents for the cancer therapy, mainly in chemo-dynamic and ferroptosis induced cancer therapy. Herein,to summarize recent advances in Fenton and Fenton like reaction mediated nanoparticles for cancer therapy, in this minireview, we first introduced the mechanisms of Fenton and Fenton like reaction and two therapeutic methods based on Fenton and Fenton like reaction, and then we introduced the well-designed nanoparticles with Fenton reaction or Fenton-like reaction characteristics for the cancer therapies. Finally its challenges and perspectives are discussed

Acid-labile chemical bonds-based nanoparticles for endosome escape and intracellular delivery

In the last years there has been a booming in the development of biological pharmaceuticals, and various nanoparticle delivery systems have been developed to overcome biological barriers to maximize the therapeutic potentials. Especially, when these drug-loaded nanoparticle systems arrive at the target cells, they must be successfully internalized into the cells, followed by the endosome escape, to release the payload in the cytoplasm. This is crucial so that the payloads are not degraded in the endosome (around pH 6.8–6.0) or lysosome (around pH 4.5). Considering the acid environment of the endosome, several studies have shown the design of different acid-labile nanoparticle delivery systems attempting to achieve endosome escape by, for example, endosomal rupture, membrane destabilization, and membrane fusion. In this mini-review, we summarize current designs in acid-labile chemical bonds for endosome escape of nanosystems. First, we briefly introduce the structural design of acid-labile nanoparticles and their endosomal escape mechanisms. Then, we review recent research work on the topic, highlighting how the nanoparticle designs can be used in endosome escape for different biomedical applications. Finally, we discuss the challenges and future perspectives in this field.Peer reviewe

Controlled release device for oral cavity

The present invention relates to a controlled release device for oral cavity, which is attached on a hard dental surface of a tooth. The attachment is done using any adhesive layer that can attach on enamel surface of a tooth or using a holder attached to the hard dental surface, to which holder the device can be attached, clipped or fastened. The device comprises of two or more polymeric materials forming a polymer matrix or matrices. The polymer matrices incorporate one or more agent(s), which release rate in the oral cavity can be con-trolled with the polymeric materials in the matrices. The invention also relates to a method producing a controlled re-lease device for delivering an agent to the oral cavity