Patients with percutaneous coronary intervention generally receive either bare metal stents or drug-eluting stents to restore the normal blood flow. However, due to the lack of stent production with an individual patient in mind, the same level of effectiveness may not be possible in treating two different clinical scenarios. This study introduces for the first time the feasibility of a patient-specific stenting process constructed from direct 3D segmentation of medical images using direct 3D printing of biodegradable polymer-graphene composite with dual drug incorporation. A biodegradable polymer-carbon composite is prepared doped with graphene nanoplatelets to achieve controlled release of combinatorics as anticoagulation and antirestenosis agents. This study develops a technology prototyped for personalized stenting. An in silico analysis is performed to optimize the stent design for printing and its prediction of sustainability under force exerted by coronary artery or blood flow. A holistic approach covering in silico to in situ-in vivo establishes the structural integrity of the polymer composite, its mechanical properties, drug loading and release control, prototyping, functional activity, safety, and feasibility of placement in coronary artery of swine.
Spatial and spectral information of a nanocarrier and its payload is crucial for the advancement of luminescence‐based imaging, disease detection, and treatment in complex biological environment. However, it remains challenging to track and quantify the delivery and localization of drugs lacking inherent fluorescence. It is demonstrated that sub 30 nm phospholipid‐stabilized nanoparticles can be detected and quantified using hyperspectral transmitted light microscopy without using a fluorophore. In two proposed model systems, phospholipid‐passivated carbon nanoparticles incorporate the drug in either free form or as a lipid‐based prodrug. Following a rigorous characterization of these nanoparticles, in vitro toxicities via loss in cell growth density and mitochondrial respiration is studied in MCF‐7 breast cancer cells. Furthermore, a detailed inhibitor based study reveals that these particles are internalized based on a clathrin‐mediated pathway, irrespective of the choice of drug formulation. Hyperspectral imaging is performed to obtain the colocalization of carbon nanoparticles and drug molecules intracellularly and can successfully be tracked while therapeutic release is quantified in 3D space. The present work demonstrates that nanoparticles and therapeutic agents can be mapped and measured simultaneously barring the requirement of a dye, thus providing new avenues in the spatiotemporal characterization and synchronous detection and quantification of payload and carrier.
Reversible switching of photoluminescence (PL) of carbon nanoparticles (CNP) can be achieved with counterionic macromolecular caging and decaging at the nanoscale. A negatively charged uncoated, "bare" CNP with high luminescence loses its PL when positively charged macromolecules are wrapped around its surface. Prepared caged carbons could regain their emission only through interaction with anionic surfactant molecules, representing anionic amphiphiles of endocytic membranes. This process could be verified by gel electrophoresis, spectroscopically and in vitro confocal imaging studies. Results indicated for the first time that luminescence switchable CNPs can be synthesized for efficient intracellular tracking. This study further supports the origin of photoluminescence in CNP as a surface phenomenon correlated a function of characteristic charged macromolecules.
Relationship of the surface physicochemical characteristics of nanoparticles with their interactions with biological entities may provide critical information for nanomedicinal applications. In this work, we have presented the systematic synthesis of sub 50nm carbon nanoparticles (CNP) presenting neutral, anionic, and cationic surface headgroups. A subset of CNPs with ~ 10, 20, and 40nm hydrodynamic sizes are synthesized with neutral surface headgroups.The cellular internalization of these CNPs was systematically quantified for the first time in various stages of breast cancer cells (early, late and metastatic), providing a parametric assessment of charge and size effects. Distinct activities are noticed with these systems as they interact with various stages of the cancer cells. Our results indicated that a metastatic breast cancer could be targeted with a nanosystem presenting anionic phosphate groups. On the contrary, for patients with late stage cancer, drugs could be delivered with sulfonate functionalized carbon nanoparticles with higher probability of intracellular transport.This study will facilitate a better understanding of nanoparticle-biologic interaction and the integration of this knowledge with pathophysiology would help to engineer nanomedicine with superior likelihoods to cross the endocytic "barrier" for delivering drug inside the cancerous cells.iii Dedicated to my parents and my sister iv ACKNOWLEDGEMENTS First and foremost, I would like to express my sincere gratitude to my advisor Professor Dipanjan Pan for his excellent guidance, care and encouragement. I am grateful to him for providing me the continuous support I needed to continue powering through this project.
Photoacoustic imaging has emerged as a promising imaging platform with a high tissue penetration depth. However, biodegradable nanoparticles, especially those for photoacoustic imaging, are rare and limited to a few polymeric agents. The development of such nanoparticles holds great promise for clinically translatable diagnostic imaging with high biocompatibility. Metabolically digestible and inherently photoacoustic imaging probes can be developed from nanoprecipitation of biliverdin, a naturally occurring heme-based pigment. The synthesis of nanoparticles composed of a biliverdin network, cross-linked with a bifunctional amine linker, is achieved where spectral tuning relies on the choice of reaction media. Nanoparticles synthesized in water or water containing sodium chloride exhibit higher absorbance and lower fluorescence compared to nanoparticles synthesized in 2-(N-morpholino) ethanesulfonic acid buffer. All nanoparticles display high absorbance at 365 and 680 nm. Excitation at near-infrared wavelengths leads to a strong photoacoustic signal, while excitation with ultraviolet wavelengths results in fluorescence emission. In vivo photoacoustic imaging experiments in mice demonstrated that the *
Chitosan/bacterial cellulose composite films containing diamond nanoparticles (NDs) with potential application as wound dressing are introduced. Microstructural studies show that NDs are uniformly dispersed in the matrix, although slight agglomeration at concentrations above 2 wt % is seen. Fourier transform infrared spectroscopy reveals formation of hydrogen bonds between NDs and the polymer matrix. X-ray diffraction analysis indicates reduced crystallinity of the polymer matrix in the presence of NDs. Approximately 3.5-fold increase in the elastic modulus of the composite film is obtained by the addition of 2 wt % NDs. The results of colorimetric analysis show that the composite films are transparent but turn to gray-like and semitransparent at high ND concentrations. Additionally, a decrease in highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) gap is also seen, which results in a red shift and higher absorption intensity towards the visible region. Mitochondrial activity assay using L929 fibroblast cells shows that the nanocomposite films are biocompatible (>90%) after 24 h incubation. Multiple lamellapodia and cell-cell interaction are shown. The results suggest that the developed films can potentially be used as a flexible platform for wound dressing.
Chiral carbon nanoparticles (CCNPs) were developed by surface passivation using the chiral ligand (-)-sparteine or (+)-sparteine (denoted (-)-SP/CNP and (+)-SP/CNP, respectively). The chirality of the prepared CCNPs was demonstrated by circular dichroism and polarimetry and employed as an enantioselective separation platform for representative racemic mixtures.
As an emerging class of carbon nanomaterials, carbon dots (CDs) have garnered many researchers' interests in the past decade due to their excellent biocompatibility, replete surface functional groups, water dispersibility, and unique photoluminescence. These extraordinary properties have opened new avenues for their advanced application in cell labeling, bioimaging, drug delivery, sensors, and energy-related devices. In this paper, we critically review recent advances in the synthetic strategies and the application of CDs for biological purposes, specifically, imaging and therapy. Finally, a perspective has been given on the potential challenges facing the translation of these materials from the bench to the market. WIREs Nanomed Nanobiotechnol 2017, 9:e1436. doi: 10.1002/wnan.1436 For further resources related to this article, please visit the WIREs website.
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