Internalization and Transport of PEGylated Lipid-Based Mixed Micelles across Caco-2 Cells Mediated by Scavenger Receptor B1

The aim of this study was to get insight into the internalization and transport of PEGylat-ed mixed micelles loaded by vitamin K, as mediated by Scavenger Receptor B1 (SR-B1) that is abundantly expressed by intestinal epithelium cells as well as by differentiated Caco-2 cells. Inhibition of SR-B1 reduced endocytosis and transport of vitamin-K-loaded 0%, 30% and 50% PEGylated mixed micelles and decreased colocalization of the micelles with SR-B1. Confocal fluorescence microscopy, fluorescence-activated cell sorting (FACS) analysis, and surface plasmon resonance (SPR) were used to study the interaction between the mixed micelles of different compositions (varying vitamin K loading and PEG content) and SR-B1. Interaction of PEGylated micelles was independent of the vitamin K content, indicating that the PEG shell prevented vitamin K exposure at the surface of the micelles and binding with the receptor and that the PEG took over the micelles’ ability to bind to the receptor. Molecular docking calculations corroborated the dual binding of both vita-min K and PEG with the binding domain of SR-B1. In conclusion, the improved colloidal stability of PEGylated mixed micelles did not compromise their cellular uptake and transport due to the affinity of PEG for SR-B1. SR-B1 is able to interact with PEGylated nanoparticles and mediates their subsequent internalization and transport.

Melanoma Cancer Therapy Using PEGylated Nanoparticles and Semiconductor Laser

Purpose: Photothermal therapy is a procedure that converts laser beam energy to heat so can disturb tumor cells. Carbon nanotubes (CNTs) have unique properties in absorption optical energy and could change optical power into heat in photothermal therapy procedures. Additionally, titanium dioxide (TiO2) NPs have a unique feature in absorbing and scattering light. Therefore, these mentioned NPs could play a synergistic role in the photothermal therapy method. Methods: CNTs and TiO2 NPs were injected into the melanoma tumor sites of cancerous mice. Then sites were excited using the laser beam (λ= 808nm, P= 2W, and I= 4W/cm2). Injected NPs caused hyperthermia in solid tumors. Tumor size assay, statistical analysis, and histopathological study of the treated cases were performed to assess the role of mentioned NPs in photothermal therapy of murine melanoma cancer. Results: The results showed that CNTs performed better than TiO2 NPs in destroying murine melanoma cancer cells in animals. Conclusion: The present study compared the photothermal activity of excited CNTs and TiO2 NPs in cancer therapy at the near-infrared spectrum of light. Tumors were destroyed selectively because of their weakened heat resistance versus normal tissue. Photothermal therapy of malignant melanoma through CNTs caused remarkable necrosis into the tumor tissues versus TiO2 NPs.

Differently PEGylated Polymer Nanoparticles for Pancreatic Cancer Delivery: Using a Novel Near-Infrared Emissive and Biodegradable Polymer as the Fluorescence Tracer

In this study, a chemically synthetic polymer, benzo[1,2-b:4,5-b′]difuran(BDF)-based donor–acceptor copolymer PBDFDTBO, was individually coated by amphiphilic poly(ethylene oxide)-block-poly(ε-caprolactone) (PEO-PCL) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy(polyethylene glycol) (DSPE-PEG or PEG-DSPE), to form stably fluorescent nanoparticles in the near-infrared (NIR) window. The physicochemical properties of the synthesized nanoparticles were characterized and compared, including their size, surface charge, and morphology. In addition, in vitro studies were also performed using two pancreatic cancer cell lines, assessing the cell viability of the PBDFDTBO-included PEGylated nanoparticles formulations. Moreover, in vivo studies were also conducted, using subcutaneous murine cancer models to investigate the polymeric nanoparticles’ circulation time, tumor accumulation, and preferred organ biodistribution. The overall results demonstrated that even with the same PEGylated surface, the hydrophobic composition anchored on the encapsulated PBDFDTBO core strongly affected the biodistribution and tumor accumulation of the nanoparticles, to a degree possibly determined by the hydrophobic interactions between the hydrophobic segment of amphiphilic polymers (DSPE or PCL moiety) and the enwrapped PBDFDTBO. Both PEGylated nanoparticles were compared to obtain an optimized coating strategy for a desired biological feature in pancreatic cancer delivery.

PEGylated Active Carbon Nanoparticles with Improved Dispersivity in Water and Potential Application in Lymphatic Targeted Therapy of Colorectal Cancer

A series of PEGylated active carbon nanoparticles were fabricated with improved dispersity in water and were explored for their ability for carrying drugs and potential application in lymphatic targeted tracing and chemotherapy of colorectal cancer. The active carbon nanoparticles were oxidized in a mild condition with 30% H2O2 solution and then mPEG-NH2 was grafted to the nanoparticles. Compared with the original carbon nanoparticles, the oxidized and PEGylated nanoparticles all present improved stability and initial solubility in water and the PEGylated nanoparticles perform best. Size of the nanoparticles was well controlled in a rational area which can fulfill the requirement for lymphatic targeting. The PEGylated nanoparticles have excellent drug loading properties and allow for sustained release under physiological conditions. The MTT results show the drug-loaded nanoparticles can effectively kill SW480 cells (Human Colon Cancer Cells). These characteristics make the PEGylated nanoparticles become a promising candidate for using as drug-loaded powder for both lymphatic targeted tracing and chemo-therapy without using suspending agent in tumor treatment.

BBB pathophysiology–independent delivery of siRNA in traumatic brain injury

Small interfering RNA (siRNA)–based therapeutics can mitigate the long-term sequelae of traumatic brain injury (TBI) but suffer from poor permeability across the blood-brain barrier (BBB). One approach to overcoming this challenge involves treatment administration while BBB is transiently breached after injury. However, it offers a limited window for therapeutic intervention and is applicable to only a subset of injuries with substantially breached BBB. We report a nanoparticle platform for BBB pathophysiology–independent delivery of siRNA in TBI. We achieved this by combined modulation of surface chemistry and coating density on nanoparticles, which maximized their active transport across BBB. Engineered nanoparticles injected within or outside the window of breached BBB in TBI mice showed threefold higher brain accumulation compared to nonengineered PEGylated nanoparticles and 50% gene silencing. Together, our data suggest that this nanoparticle platform is a promising next-generation drug delivery approach for the treatment of TBI.

Impact of dynamic sub-populations within grafted chains on the protein binding and colloidal stability of PEGylated nanoparticles.

Polyethylene glycol grafting has played a central role in preparing the surfaces of nano-probes for biological interaction; to extend blood circulation times and to modulate protein recognition and cellular uptake....