Gold nanotheranostics: future emblem of cancer nanomedicine

Cancer nanotheranostics aims at providing alternative approaches to traditional cancer diagnostics and therapies. In this context, plasmonic nanostructures especially gold nanostructures are intensely explored due to their tunable shape, size and surface plasmon resonance (SPR), better photothermal therapy (PTT) and photodynamic therapy (PDT) ability, effective contrast enhancing ability in Magnetic Resonance imaging (MRI) and Computed Tomography (CT) scan. Despite rapid breakthroughs in gold nanostructures based theranostics of cancer, the translation of gold nanostructures from bench side to human applications is still questionable. The major obstacles that have been facing by nanotheranostics are specific targeting, poor resolution and photoinstability during PTT etc. In this regard, various encouraging studies have been carried out recently to overcome few of these obstacles. Use of gold nanocomposites also overcomes the limitations of gold nanostructure probes and emerged as good nanotheranostic probe. Hence, the present article discusses the advances in gold nanostructures based cancer theranostics and mainly emphasizes on the importance of gold nanocomposites which have been designed to decipher the past questions and limitations of in vivo gold nanotheranostics.

Green synthesis of gold nanoparticles using Acai berry and Elderberry extracts and investigation of their effect on prostate and pancreatic cancer cells

Green nanotechnology has drawn major attention because of its ecofriendly and economical biosynthetic protocols. Synthesis of gold nanoparticles (AuNPs) using plant secondary metabolites is considered as a safer and cheaper option. Plants contain phytochemicals that has been used traditionally for treatment of various diseases, and proved to be non-toxic to healthy tissues. These phytochemicals play an important role in bio-reduction processes as reducing and stabilizing agents, and renders NPs selective toxicity towards diseased tissues. The study reports on the synthesis of AuNPs using Acai berry (AB) and Elderberry (EB) extracts and their anti-cancer properties. Formation of berry-AuNPs was confirmed through measurement of physico-chemical properties. The stability of the AuNPs was tested in biocompatible solutions. Anti-cancer activity of berry extracts and AuNPs was evaluated on the prostate (PC-3) and pancreatic (Panc-1) cancer cells. The berry extracts did not show toxicity to the cells, except for AB extracts on PC-3 cells at higher concentrations. The berry-AuNPs showed potential anti-cancer activities, and these effects could be further exploited for treatment of both the prostate and pancreatic cancers. Further studies are required to study the NP mechanism of action and specificity, as well as identify the phytochemicals involved in the synthesis of AuNPs.

Nanotherapeutic modulation of excitotoxicity and oxidative stress in acute brain injury

Excitotoxicity is a primary pathological process that occurs during stroke, traumatic brain injury (TBI), and global brain ischemia such as perinatal asphyxia. Excitotoxicity is triggered by an overabundance of excitatory neurotransmitters within the synapse, causing a detrimental cascade of excessive sodium and calcium influx, generation of reactive oxygen species, mitochondrial damage, and ultimately cell death. There are multiple potential points of intervention to combat excitotoxicity and downstream oxidative stress, yet there are currently no therapeutics clinically approved for this specific purpose. For a therapeutic to be effective against excitotoxicity, the therapeutic must accumulate at the disease site at the appropriate concentration at the right time. Nanotechnology can provide benefits for therapeutic delivery, including overcoming physiological obstacles such as the blood–brain barrier, protect cargo from degradation, and provide controlled release of a drug. This review evaluates the use of nano-based therapeutics to combat excitotoxicity in stroke, TBI, and hypoxia–ischemia with an emphasis on mitigating oxidative stress, and consideration of the path forward toward clinical translation.

Effect of intracellular uptake of nanoparticle-encapsulated trehalose on the hemocompatibility of allogeneic valves in the VS83 vitrification protocol

Trehalose is a disaccharide molecule consisting of two molecules of glucose. Industrially, trehalose is derived from corn starch and utilized as a drug. This study aims to examine whether the integration of nanoparticle-encapsulated trehalose to the Ice-Free Cryopreservation (IFC) method for preserving heart valves has better cell viability, benefits to protect the extracellular matrix (ECM), and reduce immune response after storage. For the experiment to be carried out, we obtained materials, and the procedures were carried out in the following manner. The initial step was the preparation of hydroxyapatite nanoparticles, followed by precipitation to acquire Apatite colloidal suspensions. Animals were obtained, and their tissue isolation and grouping were done ethically. All samples were then divided into four groups, Control group, Conventional Frozen Cryopreservation (CFC) group, IFC group, and IFC + T (IFC with the addition of 0.2 M nanoparticle-encapsulated Trehalose) group. Histological analysis was carried out via H&E staining, ECM components were stained with Modified Weigert staining, and the Gomori Ammonia method was used to stain reticular fibers. Alamar Blue assay was utilized to assess cell viability. Hemocompatibility was evaluated, and samples were processed for immunohistochemistry (TNFα and IL-10). Hemocompatibility was quantified using Terminal Complement Complex (TCC) and Neutrophil elastase (NE) as an indicator. The results of the H&E staining revealed less formation of extracellular ice crystals and intracellular vacuoles in the IFC + T group compared with all other groups. The CFC group’s cell viability showed better viability than the IFC group, but the highest viability was exhibited in the IFC + T group (70.96 ± 2.53, P < 0.0001, n = 6). In immunohistochemistry, TNFα levels were lowest in both IFC and IFC + T group, and IL-10 expression had significantly reduced in IFC and IFC + T group. The results suggested that the nanoparticle encapsulated trehalose did not show significant hemocompatibility issues on the cryopreserved heart valves.

Therapeutic applications of CRISPR/Cas9 in breast cancer and delivery potential of gold nanomaterials

Globally, approximately 1 in 4 cancers in women are diagnosed as breast cancer (BC). Despite significant advances in the diagnosis and therapy BCs, many patients develop metastases or relapses. Hence, novel therapeutic strategies are required, that can selectively and efficiently kill malignant cells. Direct targeting of the genetic and epigenetic aberrations that occur in BC development is a promising strategy to overcome the limitations of current therapies, which target the tumour phenotype. The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system, composed of only an easily modifiable single guide RNA (sgRNA) sequence bound to a Cas9 nuclease, has revolutionised genome editing due to its simplicity and efficiency compared to earlier systems. CRISPR/Cas9 and its associated catalytically inactivated dCas9 variants facilitate the knockout of overexpressed genes, correction of mutations in inactivated genes, and reprogramming of the epigenetic landscape to impair BC growth. To achieve efficient genome editing in vivo, a vector is required to deliver the components to target cells. Gold nanomaterials, including gold nanoparticles and nanoclusters, display many advantageous characteristics that have facilitated their widespread use in theranostics, as delivery vehicles, and imaging and photothermal agents. This review highlights the therapeutic applications of CRISPR/Cas9 in treating BCs, and briefly describes gold nanomaterials and their potential in CRISPR/Cas9 delivery.

Preclinical verification of the efficacy by targeting peptide-linked liposomal nanoparticles for hepatocellular carcinoma therapy

The purpose of this study was to investigate the efficacy of targeting peptides chemotherapy to overcome adverse event in the conventional chemotherapy for human hepatocellular carcinoma. Previously we reported several cancer-targeting peptides that bind specifically to cancer cells and their vascular endothelia: L-peptide (anti-cancer cell membrane), RLLDTNRPLLPY; SP-94-peptide (anti-hepatoma cell membrane), SFSHHTPILP; PC5-52-peptide (anti-tumor endothelia), SVSVGMKPSPRP; and control peptide, RLLDTNRGGGGG. In this study, these peptides were linked to liposomal iron oxide nanoparticles to localize the targeted tumor cells and endothelia, and to dextran-coated liposomal doxorubicin (L-D) to treat nonobese diabetic severe combined immunodeficient mice bearing hepatoma xenografts. Our results showed that L-peptide-linked liposomal doxorubicin could inhibit tumor growth with very mild adverse events. Use of the control peptide led to a decrease in the xenograft size but also led to marked apoptotic change in the visceral organ. In conclusion, L-peptide-linked liposomal doxorubicin, SP-94-peptide, and PC5-52-peptide can be used for the treatment of hepatoma xenografts in nonobese diabetic severe combined immunodeficient mice with minimal adverse events.

Halloysite nanotubes as a nature’s boon for biomedical applications

The arena of biomedical science has long been in quest of innovative mediums for diagnostic and therapeutic applications. The latest being the use of nanomaterials for such applications, thereby giving rise to the branch of nanomedicine. Halloysite nanotubes (HNTs) are naturally occurring tubular clay nanomaterials, made of aluminosilicate kaolin sheets rolled several times. The aluminol and siloxane groups on the surface of HNT facilitate the formation of hydrogen bonding with the biomaterials onto its surface. These properties render HNT pivotal in diverse range of applications, such as in environmental sciences, waste-water treatment, dye removal, nanoelectronics and fabrication of nanocomposites, catalytic studies, as glass coatings or anticorrosive coatings, in cosmetics, as flame retardants, stimuli response, and forensic sciences. The specific properties of HNT also lead to numerous applications in biomedicine and nanomedicine, namely drug delivery, gene delivery, tissue engineering, cancer and stem cells isolation, and bioimaging. In this review, recent developments in the use of HNT for various nanomedicinal applications have been discussed.

Engineering the hard–soft tissue interface with random-to-aligned nanofiber scaffolds

Tendon injuries can be difficult to heal and have high rates of relapse due to stress concentrations caused by scar formation and the sutures used in surgical repair. Regeneration of the tendon/ligament-to-bone interface is critical to provide functional graft integration after injury. The objective of this study is to recreate the tendon-to-bone interface using a gradient scaffold which is fabricated by a one-station electrospinning process. Two cell phenotypes were grown on a poly- ε-caprolactone nanofiber scaffold which possesses a gradual transition from random to aligned nanofiber patterns. We assessed the effects of the polymer concentration, tip-to-collector distance, and electrospinning time on the microfiber diameter and density. Osteosarcoma and fibroblast cells were seeded on the random and aligned sections of scaffolds, respectively. A random-to-aligned cocultured tissue interface which mimicked the native transition in composition of enthesis was created after 96 h culturing. The results showed that the microstructure gradient influenced the cell morphology, tissue topology, and promoted enthesis formation. This study demonstrates a heterogeneous nanofiber scaffold strategy for interfacial tissue regeneration. It provides a potential solution for mimicking transitional interface between distinct tissues, and can be further developed as a heterogeneous cellular composition platform to facilitate the formation of multi-tissue complex systems.

Astromimetics

Composite, multifunctional fine particles are likely to be at the frontier of materials science in the foreseeable future. Here we present a submicron composite particle that mimics the stratified structure of the Earth by having a zero-valent iron core, a silicate/silicide mantle, and a thin carbonaceous crust resembling the biosphere and its biotic deposits. Particles were formulated in a stable colloidal form and made to interact with various types of healthy and cancer cells in vitro. A selective anticancer activity was observed, promising from the point of view of the intended use of the particles for tumor targeting across the blood–brain barrier. As an extension of the idea underlying the fabrication of a particle mimicking the planet Earth, we propose a new field of mimetics within materials science: astromimetics. The astromimetic approach in the context of materials science consists of the design of particles after the structure of celestial bodies. With Earth being the most chemically diverse and fertile out of all the astral bodies known, it is anticipated that the great majority of astromimetic material models will fall in the domain of geo-inspired ones.

Smart niosomes of temozolomide for enhancement of brain targeting

Drug delivery to the brain is challenging because of the low permeability of blood–brain barrier, and therefore, optimum concentration of chemotherapeutics in the target area specifically for glioblastoma, an aggressive brain tumor, opens a new path of research. To achieve the goal, the oral alkylating agent temozolomide was incorporated into niosomes, and the surface was modified with chlorotoxin, a small 36 amino acid peptide discovered from the venom of scorpion Leiurus quinquestriatus. Active targeting using nanosized particles facilitates an increase in the accumulation of drugs in the cerebri by 3.04-folds. Temozolomide-loaded niosomes were prepared using conventional thin-film hydration method and characterized. Niosomes coated with chlorotoxin were produced with the size of 220 ± 1.45 nm with an entrapment efficiency of 79.09 ± 1.56%. Quantitative tissue distribution studies indicate enhanced permeation of the drug into the brain because of surface modification with less deposition in the highly perfused organs.