PDMS nanoparticles-decorated PDMS substrate promotes adhesion, proliferation and differentiation of skin cells.

Polydimethylsiloxane (PDMS) is known to be a common substrate for various cell culture-based applications. However, native PDMS is not very conducive for cell culture and hence, surface modification via cell adhesion moieties is generally needed to make it suitable especially for long-term cell culture. To address this issue, we propose to coat PDMS nanoparticles (NPs) on the surface of PDMS film to improve adhesion, proliferation and differentiation of skin cells. The proposed modification strategy introduces necessary nanotopography without altering the surface chemical properties of PDMS. Due to resemblance in the mechanical properties of PDMS with skin, PDMS NPs can recreate the native extracellular nanoenvironment of skin on the PDMS surface and provide anchoring sites for skin cells to adhere and grow. Human keratinocytes, representing 95% of the epidermal skin cells maintained their characteristic well-spread morphology with the formation of interconnected cell-sheets on this coated PDMS surface. Moreover, our in vitro immunofluorescence studies confirmed expression of distinctive epidermal protein markers on the coated surface indicating close resemblance with the native skin epidermis. Conclusively, our findings suggest that introducing nanotopography via PDMS NPs can be an effective strategy for emulating the native cellular functions of keratinocytes on PDMS based cell culture devices.

A simple, robust and scalable route to prepare sub-50 nm soft PDMS nanoparticles for intracellular delivery of anticancer drugs.

Soft nanoparticles (NPs) have recently emerged as a promising material for intracellular drug delivery. In this regard, NPs derived from polydimethylsiloxane (PDMS), an FDA approved polymer can be a suitable alternative to conventional soft NPs due to their intrinsic organelle targeting ability. However, the available synthesis methods of PDMS NPs are complicated or require inorganic fillers, forming composite NPs and compromising their native softness. Herein, for the first time, we present a simple, robust and scalable strategy for preparation of virgin sub-50 nm PDMS NPs at room temperature. The NPs are soft in nature, hydrophobic and about 30 nm in size. They are stable in physiological medium for two months and biocompatible. The NPs have been successful in delivering anticancer drug doxorubicin to mitochondria and nucleus of cervical and breast cancer cells with more than four-fold decrease in IC50 value of doxorubicin as compared to its free form. Furthermore, evaluation of cytotoxicity in reactive oxygen species detection, DNA fragmentation, apoptosis-associated gene expression and tumor spheroid growth inhibition demonstrate the PDMS NPs to be an excellent candidate for delivery of anticancer drugs in mitochondria and nucleus of cancer cells.

Peptide mediated colorimetric detection of SARS-CoV-2 using gold nanoparticles: a molecular dynamics simulation study.

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has necessitated the development of a rapid, simple yet selective naked-eye detection methodology that does not require any advanced instrumental techniques. In this study, we report our computational findings on the detection of SARS-CoV-2 using peptide- functionalized gold nanoparticles (GNPs). The peptide has been screened from angiotensin-converting enzyme 2 (ACE2) receptor situated on the surface of the host cell membrane which interacts with the spike protein of SARS-CoV-2, resulting entry of the virus into the host cell. As a result, the peptide-functionalized GNPs possess excellent affinity towards the spikes of SARS-CoV-2 and readily get aggregated once exposed to SARS-CoV-2 antigen or virus. The stability of the peptides on the surface of GNPs and their interaction with the spike protein of the virus have been investigated using coarse-grained molecular dynamic simulations. The potential of mean force calculation of spike protein confirmed strong binding between peptide and receptor-binding domain (RBD) of spike protein. Our in silico results demonstrate the potential of the peptide-functionalized GNPs in the development of simple and rapid colorimetric biosensors for clinical diagnosis.

Stable sub-100 nm PDMS nanoparticles as an intracellular drug delivery vehicle.

For the past few decades, polydimethylsiloxane (PDMS) elastomer has been used in plethora of biomedical applications. However, PDMS has not much been explored for intracellular drug delivery since the preparation of sub-100 nm particles, preferred for such kind of applications is extremely difficult owing to its innate nature to form a film. In this work, we have performed molecular dynamics (MD) simulation for developing a strategy to restrict the inherent film-forming tendency of PDMS for obtaining stable sub-100 nm PDMS nanoparticles. MD simulation results suggest that introduction of hydroxyl groups on the surface of PDMS improves its stability in the form of nanoparticles. Based on the MD simulation results, for the first time, sub-100 nm PDMS nanoparticles are prepared via in situ surface modification of PDMS with sodium hydroxide inside nanoemulsion droplets. The synthesized nanoparticles are 30-40 nm in size, extremely soft in nature, moderately hydrophobic and stable in phosphate buffered saline. In vitro results demonstrate the synthesized PDMS nanoparticles to possess excellent biocompatibility and an intrinsic capability of selective localization in mitochondria of cancer cells. Furthermore, efficient mitochondrial delivery of anticancer drug doxorubicin through PDMS nanoparticles advocates for their suitability as a potential candidate for developing advanced nanomedicine.

Biomimetic algal polysaccharide coated 3D nanofibrous scaffolds promote skin extracellular matrix formation.

Development of functional biological substitutes for skin tissue engineering applications has observed several advancements over the past few decades. In this regard, intelligent extracellular matrix (ECM) mimetic scaffolds have recently evolved as a promising paradigm by presenting instructive cues directing cell-matrix communication, tissue remodeling and homeostasis. However, orchestring multitude attributes of skin ECM yet presents an intriguing challenge to be addressed. In the present work, we have developed an in vitro skin scaffold by coating a bio-mimetic ECM cue κ-carrageenan on electrospun nanofibers for the first time. κ-Carrageenan, a natural sulfated algal polysaccharide exhibits close similarity with native glucosaminoglycans (GAGs) of skin ECM. On the other hand, electrospun nanofibers resemble the 3D nano-topographic architecture of ECM. In the coated form, κ-carrageenan could provide the biochemical cues necessary for cellular functions on the nanofibrous scaffold, thereby mimicking the native 3D microenvironment of skin ECM. The nano-architecture of the electrospun matrix is retained in the fabricated scaffold even after coating with κ-carrageenan. The developed biomimetic scaffold significantly supplements adhesion, growth, infiltration, survival and proliferation of fibroblasts. Furthermore, enhanced gene expression and excessive secretion of collagen proteins by fibroblasts communicate a conducive skin ECM micro-environment formation on the algal polysaccharide coated nanofibrous scaffold. Taken together, these findings present a simple yet effective strategy for the fabrication of ECM mimetic scaffold for promising skin tissue engineering applications.