Current Medicinal Chemistry - Volume 25, Issue 12, 2018

Background: Nanoclusters are made of a few to tens of atoms with a size below 2 nm. Compared with nanoparticles, they exhibited excellent properties, such as tunable fluorescence, ease of conjugation, high quantum yield and biocompatibility, which are highly desired in the development of cancer nanotheranostics. Hence, the metallic nanoclusters have emerged as a newcomer in cancer nanomedicines. This review aims to summarize recently developed approaches to preparing metallic nanoclusters, highlight their applications in cancer theranostics, and provide a brief outlook for the future developments of nanoclusters in nanomedicine. Method: We carried out a thorough literature search using online databases. The search was focused on a centered question. Irrelevant articles were excluded after further examination and directly relevant articles were included. The relevant articles were classified by the subjects and the information from these articles was synthesized. Results: One hundred and forty-three articles were included in this review. About eighty articles outlined the development in the synthetic methods of nanoclusters. The synthesis approaches include chemical reduction, photoreduction and so on. The progress in the application of gold and silver nanoclusters to cancer theranostics was described in fifteen and eight articles, respectively. The rest articles were about the advancements in the use of other metal nanoclusters and nanocluster nanocomposites as cancer theranostic agents. Conclusion: This review summarizes the synthesis and use of metallic nanoclusters or their nanocomposites as cancer theranostic agents. It confirms their importance, advantages and potentials in serving as a new generation of cancer theranostics in clinics.

Liposomes are a type of biomimetic nanoparticles generated from self-assembling concentric lipid bilayer enclosing an aqueous core domain. They have been attractive nanocarriers for the delivery of many drugs (e.g. radiopharmaceuticals, chemotherapeutic agents, porphyrin) and diagnostic agents (e.g. fluorescent dyes, quantum dots, Gadolinium complex and Fe3O4) by encapsulating (or adsorbing) hydrophilic one inside the liposomal aqueous core domain (or on the bilayer membrane surface), and by entrapping hydrophobic one within the liposomal bilayer. Additionally, the liposome surface can be easily conjugated with targeting molecules. Liposomes may accumulate in cancerous tissues not only passively via enhanced permeability and retention (EPR) effect, but also actively by targeting cancer cell or angiogenic marker specifically. The multimodality imaging functionalization of liposomal therapeutic agents makes them highly attractive for individualized monitoring of the in vivo cancer targeting and pharmacokinetics of liposomes loading therapeutic drugs, and predicting therapeutic efficacy in combination with the helpful information from each imaging technique. The present review article will highlight some main advances of cancer theranostic liposomes with a view to activate further research in the nanomedicine community.

Background: As nanomaterials possess attractive physicochemical properties, immense research efforts have been channeled towards their development for biological and biomedical applications. In particular, zinc nanomaterials (nZnOs) have shown great potential for use in in the medical and pharmaceutical fields, and as tools for novel antimicrobial treatment, thereby capitalizing on their unique antimicrobial effects. Methods: We conducted a literature search using databases to retrieve the relevant articles related to the synthesis, properties and current applications of nZnOs in the diagnosis and treatment of diseases. A total of 86 publications were selected for inclusion in this review. Results: Besides studies on the properties and the methodology for the synthesis of nZnOs, many studies have focused on the application of nZnOs as delivery agents, biosensors and antimicrobial agents, as well as in bioimaging. Conclusion: This review gives an overview of the current development of nZnOs for their potential use as theranostic agents. However, more comprehensive studies are needed to better assess the valuable contributions and the safety of nZnOs in nanomedicine.

Background: Nitric oxide (NO) plays important regulatory roles in a plethora of biological functions and thus holds tremendous potential to be exploited for clinical uses. However, the chemistries in the molecular design of nano-nitric oxide delivery systems is currently lacking. Objective: The overarching aim of this review is to provide the readers with the fundamentals that relate to the design of NO release molecules (NORMs), loading and releasing mechanism, as well as delivery of NORMs for nanotherapeutics. Methods: We conducted a thorough literature search on the design and synthesis of NORMs, as well as the current state-of-the-art NO compatible delivery platforms to address various clinical needs. Results: N-diazeniumdiolate and S-nitrosothiol based NO molecules are among the most widely used NORMs for anti-cancer and anti-microbial applications. The innovative integration of these NORMs with cytocompatible organic and inorganic nanocarriers enabled controlled spatiotemporal delivery and release of NO at the targeted diseased sites. Conclusion: We have provided a comprehensive summary of the fundamental chemistries underpinning the molecular design of the NORMs and critically assessed the recent advancements of nano-NO delivery systems for advanced biomedical applications.

Background: Research interest on the properties of polymer conjugated gold nanoparticle (GNP) in biomedicine is rapidly rising because of the extensive evidences for their unique properties. In the field of biomedicine, GNPs have been widely used because of their inertness and low levels of cytotoxicity. Therefore, when exposed to cells, they are less prone to exert damaging effects. GNPs are capable of being functionalized as desired and are ideal as they do not encourage undesired side reactions that might counter react with the intention of the functionalization. Biofouling is an occurrence that takes place at cellular and biological molecular level, binds non-specifically on the detection surface and forms a wrong output. This undesired incidence can be avoided by conjugating the surface of biomolecules with polymers. Densely packed repeating chains of polymers such as polyethylene glycol are capable of decreasing non-specific reactions. Applications of polymer conjugated GNPs in the field of biomedicine are as biosensors, delivery and therapeutic agents. Conclusion: Therefore, the properties and applications of polymer conjugated GNPs are studied widely as overviewed here.

Background: Coumarins are polyphenolic compounds that are often used to treat inflammatory conditions in complementary and alternative medicine. Objective: In this study, we reviewed reports of in vivo and in vitro experimental modelbased approaches investigating the potential anti-inflammatory properties of coumarins. Methods: A literature search of PUBMED, MEDLINE, Web of Science, and Scopus was performed covering the period from 1 January 2005 to 31 December 2015. The keywords used to search were ‘anti-inflammatory’ and ‘coumarin’ and ‘in vivo’ or ‘in vitro’. This search identified 425 article titles. Results: Of the 425 article titles, 127 full-text articles were reviewed, and 69 of them were included in the analysis. Most of the studies (81.2%) used in vitro assays. The studies focused on cytokines such as tumour necrosis factor (TNF), interleukin (IL)-6, and IL-1-β (55.1%), as well as oedema (46.5%), nitric oxide (NO, 23.2%), oxidative stress (21.7%), inflammatory cells (21.7%), nuclear factor (NF)-ΚB (24.6%), mitogen-activated protein kinase (MAPK, 13%), myeloperoxidase (MPO, (15.9%), cyclooxygenase (COX)-2 (14.5%), prostaglandin E2 (PGE2, 8.7%), 5-lipoxygenase (LOX, 4.3%), and adhesion molecules (7.2%). Coumarins inhibited all these parameters except for IL-10, nuclear factor erythroid 2 (NFE2)-related-factor 2 (Nrf2), and regulatory T cell (Treg) differentiation. Conclusion: In vitro methods were the most commonly used to study the antiinflammatory effects of coumarins. The results showed that coumarins exerted antiinflammatory and antioxidant activities by inhibiting NF-ΚB, nuclear factor of activated T cells (NFAT), retinoic acid-related orphan receptor γΤ (RORγΤ), and MAPK and increasing Nrf2 activation. These results suggest that coumarins could be important candidates for the development of novel anti-inflammatory therapeutic drugs.