Development of multifunctional cobalt ferrite/graphene oxide nanocomposites for magnetic resonance imaging and controlled drug delivery

Augmentation of immunogenicity can be achieved by particulate delivery of an antigen and by its co-administration with an adjuvant. However, many adjuvants initiate strong systemic inflammatory reactions in vivo, leading to potential adverse events and safety concerns. We have developed a synthetic vaccine particle (SVP) technology that enables co-encapsulation of antigen with potent adjuvants. We demonstrate that co-delivery of an antigen with a TLR7/8 or TLR9 agonist in synthetic polymer nanoparticles results in a strong augmentation of humoral and cellular immune responses with minimal systemic production of inflammatory cytokines. In contrast, antigen encapsulated into nanoparticles and admixed with free TLR7/8 agonist leads to lower immunogenicity and rapid induction of high levels of inflammatory cytokines in the serum (e.g., TNF-a and IL-6 levels are 50- to 200-fold higher upon injection of free resiquimod (R848) than of nanoparticle-encapsulated R848). Conversely, local immune stimulation as evidenced by cellular infiltration of draining lymph nodes and by intranodal cytokine production was more pronounced and persisted longer when SVP-encapsulated TLR agonists were used. The strong local immune activation achieved using a modular self-assembling nanoparticle platform markedly enhanced immunogenicity and was equally effective whether antigen and adjuvant were co-encapsulated in a single nanoparticle formulation or co-delivered in two separate nanoparticles. Moreover, particle encapsulation enabled the utilization of CpG oligonucleotides with the natural phosphodiester backbone, which are otherwise rapidly hydrolyzed by nucleases in vivo. The use of SVP may enable clinical use of potent TLR agonists as vaccine adjuvants for indications where cellular immunity or robust humoral responses are required.

Adjuvant-carrying synthetic vaccine particles augment the immune response to encapsulated antigen and exhibit strong local immune activation without inducing systemic cytokine release

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Heteroaggregation of CeO2 and TiO2 engineered nanoparticles in the aqueous phase: Application of turbiscan stability index and fluorescence excitation-emission matrix (EEM) spectra

Carbon-based nanomaterials (CNMs) have attracted great attention in biomedical applications such as cancer imaging and therapy. CNMs, which are currently used in a wide range of applications, suffer from drawbacks of toxicity and low biocompatibility. Either noncovalent or covalent functionalization of CNMs with hydrophilic and biocompatible polymers which help to block hydrophobic interactivity between CNMs and cells can greatly increase their biocompatibility by eliminating their probable toxicity towards living organisms. In this report, we present a comparison of both noncovalent and covalent functionalization approaches in order to introduce a biocompatible glycoblock copolymer onto multi-walled carbon nanotubes (CNTs) in order to enhance their potential in therapies. An anticancer drug (doxorubicin, Dox) was conjugated with two different end functionalized poly(1-O-methacryloyl-β-d-fructopyranose-b-(2-methacryloxyethoxy))benzaldehyde glycoblock copolymers, which were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization, by either noncovalent or covalent tethering. CNTs were coated separately with the synthesized drug-conjugated glycoblock copolymers and folic acid (FA) to obtain an efficient drug delivery platform for dual-targeting of glucose transporter protein (GLUT5) and folic acid receptors (FR) in breast cancer. A library of synthesized monomers, polymers and prepared glycoblock copolymer coated CNTs (hybrid-CNTs) using both approaches were comprehensively characterized by various techniques. Transmission electron microscopy measurements showed the homogeneous, smooth morphology of the prepared Dox-conjugated glycoblock copolymer coating of CNTs and confocal laser scanning microscopy images displayed successful cellular internalization of hybrid-CNTs in the MCF-7 and MDA-MB-231 human breast cancer cell lines. This research demonstrates the potential of hybrid-CNTs as a biocompatible drug delivery system as well as in vitro use of Dox-conjugated vehicles for dual receptor mediated breast cancer therapy.

/pdf/glycopolymer-decorated-multiwalled-carbon-nanotubes-for-dual-4olrzrn462.pdf

Glycopolymer decorated multiwalled carbon nanotubes for dual targeted breast cancer therapy

Considerable scope exists to vary the physical and chemical properties of nanoparticles, with subsequent impact on biological interactions; however, no accelerated process to access large nanoparticle material space is currently available, hampering the development of new nanomedicines. In particular, no clinically available nanotherapies exist for HIV populations and conventional paediatric HIV medicines are poorly available; one current paediatric formulation utilizes high ethanol concentrations to solubilize lopinavir, a poorly soluble antiretroviral. Here we apply accelerated nanomedicine discovery to generate a potential aqueous paediatric HIV nanotherapy, with clinical translation and regulatory approval for human evaluation. Our rapid small-scale screening approach yields large libraries of solid drug nanoparticles (160 individual components) targeting oral dose. Screening uses 1 mg of drug compound per library member and iterative pharmacological and chemical evaluation establishes potential candidates for progression through to clinical manufacture. The wide applicability of our strategy has implications for multiple therapy development programmes.

https://northumbria-test.eprints-hosting.org/id/document/263019

Accelerated oral nanomedicine discovery from miniaturized screening to clinical production exemplified by paediatric HIV nanotherapies.

Nanotechnology has undoubtedly brought innovation to the biomedical field, which is apparent from the advances including those in drug delivery, treatment of pathologies, imaging of disease sites, etc. The rationale behind the use of nanoparticle-based products for biomedical applications is to benefit from their unique physicochemical characteristics, mainly, size, surface area and surface functionality, to address these particles and the encapsulated payload, if any, to the desired sites in the biological system. To design appropriate nanoparticle products for biomedical applications aimed for human and/or animal use, understanding of the interplay between the physicochemistry of nanoparticles and the biophysical properties is crucial because it is the interaction of the nanoparticles at the biological interface which regulates the nanoparticles pharmacokinetics, biodistribution and safety. Also, the assessment of the potential of nanoparticles to induce undesired effects at the systemic level, organ level, cellular and sub-cellular levels is crucial for anticipating the potential risks associated with the use of nanoparticles from a safety standpoint. This review is aimed at summarizing the nanoparticle candidates for biomedical applications, and reviewing, based on the relevant literature data, the inter-relationship between nanoparticles' physicochemistry and biophysical properties in conditioning the nano–bio interactions and inturn regulating the nanoparticles pharmacokinetics, biodistribution and toxicological properties. Besides, the importance of designing relevant physiologically-based modeling approaches for the simulation and prediction of the performance and safety of new nanomaterials based on their properties has been also discussed. An important portion of the review focusses also on the description of the methodologies for a detailed assessment of the toxicological properties of the nanoparticles.

Biophysical, biopharmaceutical and toxicological significance of biomedical nanoparticles

Vascular endothelial growth factor A (VEGFA) and its kinase insert domain receptor (VEGFR2/KDR) were reported to be upregulated in chronic myeloid leukemia (CML); however, the influence of polymorphisms in VEGFA and VEGFR2 in CML pathogenesis and therapeutic response, have not yet been elucidated. We aimed to analyze these polymorphisms in 212 CML patients and 212 healthy controls by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach. The VEGFA+936C>T polymorphism did not differ significantly between the CML patients and controls. The frequency of CT genotype was higher in CML patients than in controls (25 vs. 18 %), higher in males than in females (29 vs. 18 %), was more prevalent in the patients with splenomegaly (p = 0.03), and was negatively associated with lactate dehydrogenase (LDH) levels (p = 0.01). The frequency of VEGFR2 mutant T-allele was higher in CML patients than controls (p  T polymorphism was found to have synergistic interaction with VEGFR2+1416A>T in inflating the risk for CML further (P
 interaction = 0.0002). Our results indicate that VEGFR2+1416A>T polymorphism may be a useful marker in assessing the disease progression in CML patients. In addition, VEGFA+936C>T was observed to have additive effect in inflating the risk further.

Association of Vascular Endothelial Growth Factor A (VEGFA) and its Receptor (VEGFR2) Gene Polymorphisms with Risk of Chronic Myeloid Leukemia and Influence on Clinical Outcome

Biophysical, Biopharmaceutical and Toxicological Significance of Biomedical Nanoparticles

This review has been undertaken to investigate the role of histone deacetylases (HDACs) class II genes in various cancers. Efforts in cancer research mainly aims to identify the major drug targets, develop and improve treatment regimens which eventually helps into better prognosis. One of the major challenges is the determination and mapping of involvement of molecular pathways. So, there has been large interest in developing pathways and also determining driver genes and regulators. Bioinformatics helps to evaluate huge data from wetlab researches to explore biologically relevant interactions and pathways. Emerging evidence shows that many HDACs exists as biomarkers in cancers. The objective of this study is to present a review on the major and latest findings on class II HDACs and its association in cancers. Here, we summarize the current knowledge of class II HDACs, including their features and classification, biological mechanism as well as their function and reported clinical studies in cancers. In addition, we discuss various trials and clinically available inhibitors targeting them. These results provide valuable insights which helps to identify and develop cancer specific therapeutic options.

https://www.jetir.org/papers/JETIR1806677.pdf

A. V. N. Swamy

Papers

Biophysical, biopharmaceutical and toxicological significance of biomedical nanoparticles

Association of Vascular Endothelial Growth Factor A (VEGFA) and its Receptor (VEGFR2) Gene Polymorphisms with Risk of Chronic Myeloid Leukemia and Influence on Clinical Outcome

Biophysical, Biopharmaceutical and Toxicological Significance of Biomedical Nanoparticles

HISTONE DEACETYLASES (HDACs) CLASS II GENES AS POTENTIAL DRUG TARGETS IN CANCER