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 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.
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.
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.
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.
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.