The aim of this study was to report the corneal densitometry (CD) evolution studied by Scheimpflug tomography, anterior segment optical coherence tomography (AS-OCT), and confocal microscopy changes, in patients with advanced keratoconus included in a clinical experience of advanced cell therapy using autologous humans adipose-derived adult stem cells (ADASCs) and corneal decellularized and ADASCs-recellularized human donor corneal laminas.

Methods::

This study is an interventional prospective, consecutive, randomized, comparative series of cases. Fourteen patients with keratoconus were randomly distributed into 3 groups for 3 types of surgical interventions: group 1 (G-1), autologous ADASC implantation (n = 5); group 2 (G-2), decellularized human corneal stroma (n = 5); and group 3 (G-3), autologous ADASCs + decellularized human corneal stroma (n = 4). Participants were assessed with Scheimpflug-based Oculus Pentacam CD module, AS-OCT (Visante; Carl Zeiss), and confocal microscopy (HRT3 RCM Heidelberg).

Results::

A significant improvement of 1 to 2 logMAR lines in all visual parameters in the 3 groups was obtained. The central and total CD were statistically significantly higher in G-2 compared with G-1 and G-3 compared with G-1 at the studied annular zones centered on the corneal apex (0–2, 2–6, and 6–10 mm). There was statistical significance higher in G-3 compared with G-2 at the central corneal stroma at 0–2 and 2–6 mm. The confocal microscopy findings and the AS-OCT reflected the densitometry changes.

Conclusions::

The intrastromal implantation of ADASCs produced very subtle changes in CD at the level of the central corneal stroma. However, the intrastromal implantation of decellularized corneal laminas increases it slightly, but with lower values than the implantation of recellularized laminas with ADASCs.

2022-08-01·Colloids and surfaces. B, Biointerfaces

Peptide-functionalised magnetic silk nanoparticles produced by a swirl mixer for enhanced anticancer activity of ASC-J9

Article

作者: Hadianamrei, Roja ; Zhao, Xiubo ; Brown, Stephen ; Tomeh, Mhd Anas ; Xu, Defeng

Silk fibroin is an FDA approved biopolymer for clinical applications with great potential in nanomedicine. However, silk-based nanoformulations are still facing several challenges in processing and drug delivery efficiency (such as reproducibility and targetability), especially in cancer therapy. To address these challenges, robust and controllable production methods are required for generating nanocarriers with desired properties. This study aimed to develop a novel method for the production of peptide-functionalized magnetic silk nanoparticles with higher selectivity for cancer cells for targeted delivery of the hydrophobic anticancer agent ASC-J9. A new microfluidic device with a swirl mixer was designed to fabricate magnetic silk nanoparticles (MSNP) with desired size and narrow size distribution. The surface of MSNPs was functionalized with a cationic amphiphilic anticancer peptide, G(IIKK)₃I-NH₂ (G3), to enhance their selectivity towards cancer cells. The G3-MSNPs increased the cellular uptake and anticancer activity of G3 in HCT 116 colorectal cancer cells compared to free G3. Moreover, the G3-MSNPs exhibited considerably higher cellular uptake and cytotoxicity in HCT 116 colorectal cancer cells compared to normal cells (HDFs). Encapsulating ASC-J9 in G3-MSNPs resulted in augmented anticancer activity compared to free ASC-J9 and non-functionalized ASC-J9 loaded MSNPs within its biological half-life. Hence, functionalizing MSNPs with G3 enabled targeted delivery of ASC-J9 to cancer cells and enhanced its anticancer effect. Functionalization of nanoparticles with anticancer peptides could be regarded as a new strategy for targeted delivery and enhanced efficiency of anticancer drugs. Furthermore, the microfluidic device introduced in this paper offers a robust and reproducible method for fabrication of small sized homogenous nanoparticles.

2021-10-27·ACS applied materials & interfaces2区 · 材料科学

Designed Antitumor Peptide for Targeted siRNA Delivery into Cancer Spheroids

2区 · 材料科学

Article

作者: Wilkinson, Robert N ; Zhao, Xiubo ; Cirillo, Silvia ; Brown, Stephen ; Tomeh, Mhd Anas ; Hill, Chris

Antimicrobial/anticancer peptides (AMPs/ACPs) have shown promising results as new therapeutic agents in cancer thearpy. Among them, the designed amphiphilic α-helical peptide G(IIKK)₃I-NH₂ (G3) displayed great affinity and specificity in targeting cancer cells. Here, we report new insights on how G3 penetrates cancer cells. G3 showed high specificity to HCT-116 colon cancer cells compared to the HDFs (human neonatal primary dermal fibroblasts) control. With high concentrations of peptide, a clear cancer cell membrane disruption was observed through SEM. Gene knockdown of the endocytic pathways demonstrated that an energy-dependent endocytic pathway is required for the uptake of the peptide. In addition, G3 can protect and selectively deliver siRNAs into cancer cells and successfully modulated their gene expression. Gene delivery was also tested in 3D cancer spheroids and showed deep penetration delivery into the cancer spheroids. Finally, the in vivo toxicity of G3 was evaluated on zebrafish embryos, showing an increasing toxicity effect with concentration. However, the toxicity of the peptide was attenuated when complexed with siRNA. In addition, negligible toxicity was observed at the concentration range for efficient gene delivery. The current results demonstrate that G3 is promising as an excellent agent for cancer therapy.

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