Nanoparticle Rigidity for Brain Tumor Cell Uptake.

Nanoparticles (NPs) have emerged as versatile and widely used platforms for a variety of biomedical applications. For delivery purposes, while some of NPs' physiochemical aspects such as size and shape have been extensively studied, their mechanical properties remain understudied. Recent studies have reported NPs' rigidity as a significant factor for their cell interactions and uptake. Here, we aim to study how NPs' rigidity affects their interactions with brain glioma tumor cells. To produce NPs with different rigidities, we encapsulate poly(ethylene glycol) diacrylate (PEGDA) of different volume ratios (0, 10, 30 v/v%) within the lumen of nanoliposomes and study the uptake of these NPs in a glioblastoma cell line U87. PEGDA with volume ratios of 10 and 30% were selected to provide a significant increase of the elastic modulus of the hydrogel (0.1 to 4 MPa) as determined by compression testing. Dynamic light scattering (DLS) and zeta potential measurements indicated that despite differences in their core formulation, all examined NPs had a similar size range (106 to 132 nm) and surface charge (-2.0 to -3.0 mV). Confocal microscopy revealed that all NP groups accumulated inside U87 cells, and flow cytometry data showed that liposomes with a gel core (10 and 30 v/v% PEGDA) had significantly higher cellular uptake (up to 9-fold), compared to liposomes with an aqueous core. Notably, we did not find any substantial difference between the uptake of liposomes with PEGDA core of 10 and 30% volume ratios. Clinical Relevance- By providing an insight into how NP rigidity influences glioma tumor cellular uptake, this work would enable development of more effective therapeutics for brain cancer.

Organic Semiconductor Nanotubes for Electrochemical Devices.

Electrochemical devices that transform electrical energy to mechanical energy through an electrochemical process have numerous applications ranging from soft robotics and micropumps to autofocus microlenses and bioelectronics. To date, achievement of large deformation strains and fast response times remains a challenge for electrochemical actuator devices operating in liquid wherein drag forces restrict the actuator motion and electrode materials/structures limit the ion transportation and accumulation. We report results for electrochemical actuators, electrochemical mass transfers, and electrochemical dynamics made from organic semiconductors (OSNTs). Our OSNTs electrochemical device exhibits high actuation performance with fast ion transport and accumulation and tunable dynamics in liquid and gel-polymer electrolytes. This device demonstrates an excellent performance, including low power consumption/strain, a large deformation, fast response, and excellent actuation stability. This outstanding performance stems from enormous effective surface area of nanotubular structure that facilitates ion transport and accumulation resulting in high electroactivity and durability. We utilize experimental studies of motion and mass transport along with the theoretical analysis for a variable-mass system to establish the dynamics of the electrochemical device and to introduce a modified form of Euler-Bernoulli's deflection equation for the OSNTs. Ultimately, we demonstrate a state-of-the-art miniaturized device composed of multiple microactuators for potential biomedical application. This work provides new opportunities for next generation electrochemical devices that can be utilized in artificial muscles and biomedical devices.

Preparation and characterization of size-controlled glioma spheroids using agarose hydrogel microwells.

Treatment of glioblastoma, the most common and aggressive type of primary brain tumors, is a major medical challenge and the development of new alternatives requires simple yet realistic models for these tumors. In vitro spheroid models offer attractive platforms to mimic the tumor behavior in vivo and have thus, been increasingly applied for assessment of drug efficacy in various tumors. The aim of this study was to produce and characterize size-controlled U251 glioma spheroids towards application in glioma drug evaluation studies. To this end, we fabricated agarose hydrogel microwells with cylindrical shape and diameters of 70-700 µm and applied these wells without any surface modification for glioma spheroid formation. The resultant spheroids were homogeneous in size and shape, exhibited high cell viability (> 90%), and had a similar growth rate to that of natural brain tumors. The final size of spheroids depended on cell seeding density and microwell size. The spheroids' volume increased linearly with the cell seeding density and the rate of this change increased with the well size. Lastly, we tested the therapeutic effect of an anti-cancer drug, Di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT) on the resultant glioma spheroids and demonstrated the applicability of this spheroid model for drug efficacy studies.

Conducting Polymer Microtubes for Bioactuators.

Conducting polymer (CP) actuators are promising devices for biomedical applications such as artificial muscles and drug delivery systems. Here, we report a tri-layer actuator based on poly(pyrrole) (PPy) microtubes (PPy MTs) doped with poly(sodium-p-styrenesulfonate) (PSS) and constructed on a passive layer of gold-coated poly-propylene (PP) film. The PPy MTs were fabricated using electrochemical deposition of PPy around poly(lactic-co-glycolic acid) (PLGA) fiber templates, followed by template removal. The PPy MTs were subjected to a redox process using cyclic voltammetry in 0.1 M NaPSS electrolyte solution as the potential was swept between -0.8 V and +0.4 V for 5 cycles at the scan rates of 10, 50, 100, and 200 mV/s. The bending behavior of the PPy MTs actuator was investigated by measuring the deflection of actuator tip resulting from the expansion/contraction strain of PPy MTs. The PPy MTs actuator showed a reversible bending movement during each potential cycle. The maximum deflection of actuator decreased by increasing the scan rate that was confirmed by calculating the actuation strain generated during each cycle at various scan rates.

Preparation of Gel-Liposome Nanoparticles for Drug Delivery Applications.

Liposomes are amongst the most effective delivery vehicles developed to date. Despite many advantages including biocompatibility, biodegradability, and the ability to carry both hydrophilic and lipophilic compounds, liposomes suffer from low physical stability. This limitation can be effectively addressed by inclusion of a polymeric scaffold within the core of liposomes. Given the versatility of poly (ethylene glycol) (PEG) hydrogels, these polymers have a great potential for the use in liposomal core. As a step towards the development of a robust liposomal delivery platform, here we aim to develop a simple and reliable technique for the fabrication of liposomes with PEG gel cores. We assess the resultant nanoparticles using scanning electron microscopy and dynamic light scattering and demonstrate that the presented approach can successfully produce gel-liposome nanoparticles with spherical shape and 150-200 nm size. These nanoparticles are further evaluated for colloidal stability in physiological solution. Moreover, we demonstrate the versatility of this method by studying the effect of changing (A) the membrane composition in liposomes, and (B) the hydrogel concentration in liposomal core, on the formation of gel-liposome particles.