An Analysis of the Capturing and Passing Ability of a DNA Origami Nanocarrier with the Aid of Molecular Dynamics Simulation.

The present article aims to investigate the ability of a DNA origami nanocarrier to successfully capture a cargo using molecular dynamics (MD) simulation. In addition, the passage of the cargo through the nanocarrier was analyzed by steered molecular dynamics (SMD) simulation. The proposed DNA origami nanocarrier is a nanotube that consists of six double helices in which a positively charged nanocargo was placed. Since the stability of the nanocarrier has been considered one of the obstacles to nanocargo transportation, different cross-sectional areas of the nanocarrier were considered as measures to analyze its structural stability. The results eventually showed that the proposed nanocarrier is able to retain the cargo while maintaining its structural stability. The analysis also revealed that the presence of the cargo increases the structural stability in parts of the nanocarrier. SMD simulation demonstrated that a feasible amount of force is required to separate the cargo and pass it through the nanocarrier, which can provide useful information in the field of smart drug delivery.

Dendrimer-Functionalized Nanodiamonds as Safe and Efficient Drug Carriers for Cancer Therapy: Nucleus Penetrating Nanoparticles.

Nanodiamonds (NDs) are increasingly being assessed as potential candidates for drug delivery in cancer cells and they hold great promise in overcoming the side effects of traditional chemotherapeutics. In the current work, carboxylic acid functionalized nanodiamonds (ND-COOH) were covalently modified with poly(amidoamine) dendrimer (PAMAM) to form amine-terminated nanodiamonds (NP). Unlike ND-COOH, the chemically modified nanodiamond platform NP revealed a pH-independent aqueous dispersion stability, enhancing its potential as an effective carrier. Physical encapsulation of poorly water soluble cabazitaxel (CTX) drug on NP formed ND-PAMAM-CTX (NPC) nanoconjugates and substantially reduced the size of CTX from micrometer to nanometer. CTX was localized within the pores of nanoparticle aggregates and the cavities of the PAMAM dendrimer, thus facilitating the loaded drug's controlled and sustained release. NPC's cumulative CTX release efficiency was determined to be ∼95% at pH 4 after 96 h. A high cellular uptake of NPC both within the cytoplasm and nucleus of U87 cells is confirmed, accounting for a reduced IC50 value (1 nM). Both the cell cycle and Western blot analyses confirmed enhanced cell death and suppressed tubulin protein expression in NPC-treated cells. A significantly high inhibition to cell division with early apoptosis and reduced metastasis demonstrates the effective loading of CTX dosages on the nanocarrier. The present work highlights the potential of a newly designed nanocarrier NP as an efficient nanocargo for cellular delivery applications and may provide future insights to treat one of the most aggressive tumors in neuro-oncological research, glioblastoma multiforme (GBM).

Intratumoral VEGF nanotrapper reduces gliobastoma vascularization and tumor cell mass.

Glioblastoma multiforme (GBM) is the most aggressive and invasive malignant brain cancer. GBM is characterized by a dramatic metabolic imbalance leading to increased secretion of the pro-angiogenic factor VEGF and subsequent abnormal tumor vascularization. In 2009, FDA approved the intravenous administration of bevacizumab, an anti-VEGF monoclonal antibody, as a therapeutic agent for patients with GBM. However, the number of systemic side effects and reduced accessibility of bevacizumab to the central nervous system and consequently to the GBM tumor mass limited its effectiveness in improving patient survival. In this study, we combined experimental and computational modelling to quantitatively characterize the dynamics of VEGF secretion and turnover in GBM and in normal brain cells and simultaneous monitoring of vessel growth. We showed that sequestration of VEGF inside GBM cells, can be used as a novel target for improved bevacizumab-based therapy. We have engineered the VEGF nanotrapper, a cargo system that allows cellular uptake of bevacizumab and inhibits VEGF secretion required for angiogenesis activation and development. Here, we show the therapeutic efficacy of this nanocargo in reducing vascularization and tumor cell mass of GBM in vitro and in vivo cancer models.

Topotecan-loaded thermosensitive nanocargo for tumor therapy: In vitro and in vivo analyses.

This study demonstrates the development of topotecan (TCN) loaded thermosensitive nanocargos (TCN-TS-NC) for intramuscular (IM) administration with enhanced antitumor activity. In this regards, TCN loaded temperature dependent solid lipid nanoparticles (SLNs) were prepared with micro-emulsion method, which were then incorporated into temperature sensitive poloxamer solution to develop TCN-TS-NC. The particle size, entrapment efficiency (%EE), zeta potential and transmission electron microscopy (TEM) analysis of the TCN-TS-NC were performed. Moreover, the inject-ability, release pattern, apoptosis, cellular uptake, pharmacokinetics and antitumor studies of the TCN-TS-NC were attained and compared with TCN solution and TCN-Emulgel (poloxamer solution containing TCN). At room temperature, the TCN loaded SLNs were solid and poloxamer solution remains liquid, however, TCN loaded SLNs melted to liquid and Emulgel converted into gel from, at body temperature, resulting controlled release of the incorporated drug. The TCN-TS-NC showed enhanced cellular uptake and better apoptosis. Similarly, it reduces Cmax and sustained its level for a significantly longer time in rats, as compared to the TCN-Emulgel and TCN solution. Moreover, a significantly improved antitumor activity was observed in TCN-TS-NC treated tumor bearing athymic nude mice when compared with the control, TCN solution and TCN-Emulgel applied mice. Thus, the TCN-TS-NC system showed control release of the drug with no initial fast effect. Furthermore, it enhanced the antitumor activity of TCN with comparatively no toxicity. It is therefore concluded that TCN-TS-NC could be a potentially more suitable drug delivery system for the delivery of TCN.

Developing a Programmable, Self-Assembling Squash Leaf Curl China Virus (SLCCNV) Capsid Proteins into "Nanocargo"-like Architecture.

A new era has begun in which pathogens have become useful scaffolds for nanotechnology applications. In this research/study, an attempt has been made to generate an empty cargo-like architecture from a plant pathogenic virus named Squash leaf curl China virus (SLCCNV). In this approach, SLCCNV coat protein monomers are obtained efficiently by using a yeast Pichia pastoris expression system. Further, dialysis of purified SLCCNV-CP monomers against various pH modified (5-10) disassembly and assembly buffers produced a self-assembled "Nanocargo"-like architecture, which also exhibited an ability to encapsulate magnetic nanoparticles in vitro. Bioinformatics tools were also utilized to predict the possible self-assembly kinetics and bioconjugation sites of coat protein monomers. Significantly, an in vitro biocompatibility study using SLCCNV-Nanocargo particles showed low toxicity to the cells, which eventually proved as a potential nanobiomaterial for biomedical applications.

Poly(N-vinyl caprolactam) grown on nanographene oxide as an effective nanocargo for drug delivery.

This study evaluated graphene oxide functionalized covalently with poly N-vinyl caprolactam (GO-PVCL) via in situ atomic transfer radical polymerization (ATRP), as a nano-cargo carrier for the efficient delivery of drugs into cells. Water-soluble GO-PVCL exhibited excellent stability in physiological solutions. An anti-cancer drug, camptothecin (CPT), was then loaded onto GO-PVCL with a high payload (20%) through π-π stacking and hydrophobic interactions, and its release could be controlled by varying the pH. PVCL grafted onto GO offers an additional advantage of targeted delivery according to temperature. GO-PVCL showed no obvious toxicity, whereas the CPT-loaded GO-PVCL showed high potency in killing cancer cells in vitro. The drug transportation mechanism was found to be energy-dependent endocytosis. Overall, this study revealed GO-PVCL to be a promising drug delivery vector with high biocompatibility, solubility and stability in physiological solutions, and good payload capacity owing to its small size, low cost, large specific area, ready scalability, and useful non-covalent interactions. This material is expected to be a novel material propitious for biomedical applications.