Muhymin Islam

Micro+nanotexturing of substrates to enhance ligand-assisted cancer cell isolation.

This paper presents a simple approach to create a two-tiered surface for superior cancer cell isolation. The idea is inspired by the interactions of cells with a nanotextured basement membrane. The texture mimicked the extracellular matrix and basement membrane for superior target cell adhesion. Prepared micro+nanotextured surfaces showed enhanced cell capture. Preparation of the two-tiered surface was done using micro- and nanotexturing and was easily reproducible. It has been shown before that the larger surface area of a nanotextured surface assists the cells attachment through surface-anchored ligands. Taking it a step further, ligand functionalized two-level micro+nanotextured surfaces improved the sensitivity of the cancer cell isolation over simple flat nanotexturing. The isolation efficiency increased by 208% compared to the surface with a single-level nanotexture. The two-tiered surface was compatible with previously reported nanotextured devices used for cancer cell isolation. Micro-texture on the glass surface was created using simple sand gritting, followed by reactive ion etching (RIE) of the entire surface. The approach could create large surface areas within a short time while maintaining superior cell isolation efficiency.

PLGA Micro- and Nanoparticles Loaded Into Gelatin Scaffold for Controlled Drug Release

Curcumin and bovine serum albumin (BSA) were used as model drugs and loaded into microand nanoparticles of biodegradable poly(lactic-co-glycolic acid) (PLGA). The PLGA was incorporated into hydrophilic and biocompatible gelatin scaffolds to design a controlled drug release system. The gelatin scaffolds were cross-linked using glutaraldehyde. The controlled delivery of drugs from biologically active PLGA microand nanoparticles was measured and these showed consistent release for 30 days. Curcuminand BSA-loaded PLGA micro/nanoparticles-based gelatin scaffolds define a novel approach to embed multiple drug molecules to overcome multidrug resistance as well as depict a new type of biocompatible and biodegradable implant. Such scaffold constructs can be used for breast implants after lumpectomy to not only overcome cosmetic issues, but also to provide sustained drug release during healing process. In one type of construct, only BSA-loaded microparticles were mixed with gelatin, while in the other type of construct, both BSAand curcumin-loaded PLGA microparticles were embedded. BSAand curcumin-loaded nanoparticles were also embedded into gelatin constructs to see the effects of particle size on drug release. After 30 days, cumulative BSA release from PLGA microand nanoparticles embedded in gelatin scaffold were measured to be 69.87% and 86.11%, respectively. The cumulative release of curcumin was measured to be 53.11% and 60.42% from curcumin-loaded PLGA microand nanoparticles, respectively. A statistically significant difference was seen in cumulative drug release from these scaffolds (p value <; 0.05).

Effects of Nanotexture on Electrical Profiling of Single Tumor Cell and Detection of Cancer from Blood in Microfluidic Channels.

Microfluidic channels have been implemented to detect cancer cells from blood using electrical measurement of each single cell from the sample. Every cell provided characteristic current profile based on its mechano-physical properties. Cancer cells not only showed higher translocation time and peak amplitude compared to blood cells, their pulse shape was also distinctively different. Prevalent microfluidic channels are plain but we created nanotexture on the channel walls using micro reactive ion etching (micro-RIE). The translocation behaviors of the metastatic renal cancer cells through plain and nanotextured PDMS microchannels showed clear differences. Nanotexture enhanced the cell-surface interactions and more than 50% tumor cells exhibited slower translocation through nanotextured channels compared to plain devices. On the other hand, most of the blood cells had very similar characteristics in both channels. Only 7.63% blood cells had slower translocation in nanotextured microchannels. The tumor cell detection efficiency from whole blood increased by 14% in nanotextured microchannels compared to plain channels. This interesting effect of nanotexture on translocation behavior of tumor cells is important for the early detection of cancer.

Nanotextured polymer substrates show enhanced cancer cell isolation and cell culture

Detection of circulating tumor cells (CTCs) in the early stages of cancer is a great challenge because of their exceedingly small concentration. There are only a few approaches sensitive enough to differentiate tumor cells from the plethora of other cells in a sample like blood. In order to detect CTCs, several antibodies and aptamers have already shown high affinity. Nanotexture can be used to mimic basement membrane to further enhance this affinity. This article reports an approach to fabricate nanotextured polydimethylsiloxane (PDMS) substrates using micro reactive ion etching (micro-RIE). Three recipes were used to prepare nanotextured PDMS using oxygen and carbon tetrafluoride. Micro-RIE provided better control on surface properties. Nanotexturing improved the affinity of PDMS surfaces to capture cancer cells using surface immobilized aptamers against cell membrane overexpressed with epidermal growth factor receptors. In all cases, nanotexture of PDMS increased the effective surface area by creating nanoscale roughness on the surface. Nanotexture also enhanced the growth rate of cultured cells compared to plain surfaces. A comparison among the three nanotextured surfaces demonstrated an almost linear relationship between the surface roughness and density of captured tumor cells. The nanotextured PDMS mimicked biophysical environments for cells to grow faster. This can have many implications in microfluidic platforms used for cell handling.

Cell Elasticity-based Microfluidic Label-free Isolation of Metastatic Tumor Cells

Aims: Circulating tumor cells (CTCs) have significant diagnostic value for cancer patients. We report a label -free, simple and rapid microchannel filter type device for isolation ofknown metastatic cancercells based on their mechano-physical properties like size and deformability. Study Design:Metastatic renal cancer cells were highly elastic and squeeze d through microchannels much smaller than their size. Using a reverse -selectivity approach, the number of microchannels and their dimensionswere varied to optimize and reduce the shear stress o n tumor cells such that these did

Salt-Leaching Synthesis of Porous PLGA Nanoparticles

Poly(lactic-co-glycolic acid) (PLGA) nanoparticles are widely used for controlled delivery of bioactive agents in therapeutic applications. These nanoparticles show bioavailability, better encapsulation, controlled release, biocompatibility, and in vivo biodegradability. This paper reports a novel approach to synthesize porous PLGA nanoparticles and their use as controlled release vehicles. Bovine serum albumin (BSA) loaded PLGA nanoparticles (porous and nonporous) were synthesized using water-in-oil-in-water double emulsion method. Specifically, PLGA nanoparticles were prepared using chloroform and polyvinyl alcohol, and freeze drying was employed for the phase separation to obtain the nanoparticles. The porous nanoparticles were prepared through the salt-leaching process where sodium bicarbonate was used as an extractable porogen. In vitro drug release behavior of porous and nonporous nanoparticles was monitored over a period of 30 days. A much more enhanced BSA release was observed in case of porous polymeric nanoparticles when compared to nonporous nanoparticles. The characterization was done using laser scattering, zeta potential analysis, and scanning electron microscopy. The drug loading efficiencies for BSA in porous and nonporous PLGA nanoparticles were 65.50% and 77.59%, respectively. Over a period of 30 days, the cumulative BSA released from PLGA porous and nonporous nanoparticles were measured to be 87.41% and 59.91%, respectively. The synthesis of porous nanoparticles with this novel, rapid, and inexpensive method opens a new horizon of using a wide range of cheap and easily-accessible water-soluble salts that can be extracted through leaching process to introduce porous morphology on the nanoparticle surfaces. The porous nanoparticles can have useful applications in controlled drug delivery systems.