Showing papers by "Nikhil R. Jana published in 2021"

Nanoparticle Size Effects in Biomedical Applications

Abstract: Nanoparticle size plays a central role in determining material properties and performance in biomedical applications. A wide variety of functional nanomaterials and nano-bioconjugates have been developed for monitoring biochemical activity, controlling biological functions, and therapeutic applications. This review focuses on the role of nanoparticle size (typically in the range of 1–100 nm) in various biomedical applications, the origin of such a size effect, and the optimum size requirement for the best performance in different biomedical applications. First, we discuss various nanoscale units present in life processes along with their size and functional role. Next, we discuss the size-dependent properties of some well-known nanoparticles and how those properties are exploited in different biomedical applications. Next, we discuss the size-dependent performance of functional nanomaterials and nano-bioconjugates that are used in various biomedical applications. Then, we highlight some of the best designed nanoparticles of optimum size for specific biomedical applications. Finally, we attempt to correlate the origin of the evolutionary selection of various nanoscale units in life processes toward specific biological functions.

Cotton Modified with Silica Nanoparticles, N,F Codoped TiO2 Nanoparticles, and Octadecyltrimethoxysilane for Textiles with Self-Cleaning and Visible Light-Based Cleaning Properties

Abstract: Cotton is widely used in various forms in textile industries, medical appliances, and different commercial materials and appropriate surface modification of cotton can greatly enhance its applicati...

Chemically Designed Nanoscale Materials for Controlling Cellular Processes.

Abstract: Nanoparticles are widely used in various biomedical applications as drug delivery carriers, imaging probes, single-molecule tracking/detection probes, artificial chaperones for inhibiting protein aggregation, and photodynamic therapy materials. One key parameter of these applications is the ability of the nanoparticles to enter into the cell cytoplasm, target different subcellular compartments, and control intracellular processes. This is particularly the case because nanoparticles are designed to interact with subcellular components for the required biomedical performance. However, cells are protected from their surroundings by the cell membrane, which exerts strict control over entry of foreign materials. Thus, nanoparticles need to be designed appropriately so that they can readily cross the cell membrane, target subcellular compartments, and control intracellular processes.In the past few decades there have been great advancements in understanding the principles of cellular uptake of foreign materials. In particular, it has been shown that internalization of foreign materials (small molecules, macromolecules, nanoparticles) is size-dependent: endocytotic uptake of materials requires sizes greater than 10 nm, and materials with sizes of 10-100 nm usually enter into cells by energy-dependent endocytosis via biomembrane-coated vesicles. Direct access to the cytosol is limited to very specific conditions, and endosomal escape of material appears to be the most practical approach for intracellular processing.In this Account, we describe how cellular uptake and intracellular processing of nanoscale materials can be controlled by appropriate design of size and surface chemistry. We first describe the cell membrane structure and principles of cellular uptake of foreign materials followed by their subcellular trafficking. Next, we discuss the designed surface chemistry of a 5-50 nm particle that offers preferential lipid-raft/caveolae-mediated endocytosis over clathrin-mediated endocytosis with minimum endosomal/lysosomal trafficking or energy-independent direct cell membrane translocation (without endocytosis) followed by cytosolic delivery without endosomal/lysosomal trafficking. In particular, we emphasize that the zwitterionic-lipophilic surface property of a nanoparticle offers preferential interaction with the lipid raft region of the cell membrane followed by lipid raft uptake, whereas a lower number of affinity biomolecules (<25) on the nanoparticle surface offers caveolae/lipid-raft uptake, while an arginine/guanidinium-terminated surface along with a size of <10 nm offers direct cell membrane translocation. Finally, we discuss how nanoprobes can be designed by adapting these surface chemistry and size preference principles so that they can readily enter into the cell, label different subcellular compartments, and control intracellular processes such as trafficking kinetics, exocytosis, autophagy, amyloid aggregation, and clearance of toxic amyloid aggregates. The Account ends with a Conclusions and Outlook where we discuss a vision for the development of subcellular targeting nanodrugs and imaging nanoprobes by adapting to these surface chemistry principles.

Biomedical Applications of Functional Polyaspartamide-Based Materials

Abstract: Biocompatible and biodegradable polymeric formulations are required in diverse biomedical applications. Among various polymers, polyaspartamide-derivative-based formulations are extensively employe...

Phosphate-Dependent Colloidal Stability Controls Nonendocytic Cell Delivery of Arginine-Terminated Nanoparticles.

Abstract: Although arginine-rich polymers and peptides are extensively used as delivery carriers for drugs/proteins/nanoparticles, their cell delivery mechanism is not clearly understood. Recent studies show that arginine-terminated nanoparticles can enter into a cell via a nonendocytic approach that involves direct membrane penetration. However, poor colloidal stability of arginine-terminated nanoparticles under physiological conditions restricts their application potential. Here, we show that the nonendocytic cell delivery of arginine-terminated nanoparticles is controlled by their colloidal stability in the presence of phosphates. We have designed arginine-terminated quantum dots (QDs) of 10-15 nm hydrodynamic size, which enter into the cell via a nonendocytic approach, provided that they are colloidal and dispersed during cellular uptake. We have demonstrated that arginine-terminated QDs rapidly precipitate in the presence of monophosphates or polyphosphates, and polyphosphates have a stronger effect than monophosphates. Introducing polyethylene glycol at the QD surface can improve the colloidal stability against phosphates. Control experiments show that amine/ammonium-terminated cationic QDs of similar sizes do not have such a type of phosphate-dependent precipitation issue. We propose that arginine-terminated colloidal nanoparticles have a unique advantage over amine/ammonium-terminated nanoparticles as they can bind with the cell membrane phosphate via guanidinium-phosphate salt bridging. Bulk phosphate provides reversibility in this binding interaction so that nonendocytic cell uptake occurs via charge compensation of cationic nanoparticles without membrane damage. The developed surface chemistry approach and the proposed mechanisms can be adapted to other nanoparticles for efficient cell delivery and for designing delivery carriers.

Penetration and preferential binding of charged nanoparticles to mixed lipid monolayers: interplay of lipid packing and charge density.

Abstract: Designing of nanoparticles (NPs) for biomedical applications or mitigating their cytotoxic effects requires microscopic understanding of their interactions with cell membranes. Such insight is best obtained by studying model biomembranes which, however, need to replicate actual cell membranes, especially their compositional heterogeneity and charge. In this work we have investigated the role of lipid charge density and packing of phase separated Langmuir monolayers in the penetration and phase specificity of charged quantum dot (QD) binding. Using an ordered and anionic charged lipid in combination with uncharged but variable stiffness lipids we demonstrate how the subtle interplay of zwitterionic lipid packing and anionic lipid charge density can affect cationic nanoparticle penetration and phase specific binding. Under identical subphase pH, the membrane with higher anionic charge density displays higher NP penetration. We also observe coalescence of charged lipid rafts floating amidst a more fluidic zwitterionic lipid matrix due to the phase specificity of QD binding. Our results suggest effective strategies which can be used to design NPs for diverse biomedical applications as well as to devise remedial actions against their harmful cytotoxic effects especially against respiratory diseases.

Selective capturing and fluorescence “turn on” detection of dibutyl phthalate using a molecular imprinted nanocomposite

Abstract: Dibutyl phthalate is a potential endocrine-disrupting chemical, and its detection in the environment/water at trace levels is a critical issue to avoid its consumption by humans. However, the selective detection of dibutyl phthalate via a simple and cost-effective approach is challenging. Here, we report the fluorescence-based selective detection of dibutyl phthalate at micromolar concentration without using any antibodies. We have designed a nanocomposite made of graphene oxide and poly-cyclodextrin with the molecular imprint of dibutyl phthalate. The molecular imprint inside the nanocomposite offers selective capture of dibutyl phthalate, and graphene oxide offers fluorescence “turn on” detection via a competitive binding interaction with fluorescein. A nanocomposite-incorporating a paper strip is developed for the simple read out detection of dibutyl phthalate in contaminated water. The developed method can be used for the selective detection of dibutyl phthalate in water, and the approach can be extended for the detection/separation of other environmental pollutants.

Compressibility of Multicomponent, Charged Model Biomembranes Tunes Permeation of Cationic Nanoparticles.

Abstract: Cells respond to external stress by altering their membrane lipid composition to maintain fluidity, integrity and net charge. However, in interactions with charged nanoparticles (NPs), altering membrane charge could adversely affect its ability to transport ions across the cell membrane. Hence, it is important to understand possible pathways by which cells could alter zwitterionic lipid composition to respond to NPs without compromising membrane integrity and charge. Here, we report in situ synchrotron X-ray reflectivity (XR) measurements to monitor the interaction of cationic NPs in the form of quantum dots, with phase-separated supported lipid bilayers of different compositions containing an anionic lipid and zwitterionic lipids having variable degrees of stiffness. We observe that the extent of NP penetration into the respective membranes, as estimated from XR data analysis, is inversely related to membrane compression moduli, which was tuned by altering the stiffness of the zwitterionic lipid component. For a particular membrane composition with a discernible height difference between ordered and disordered phases, we were able to observe subtle correlations between the extent of charge on the NPs and the specificity to bind to the charged and ordered phase, contrary to that observed earlier for phase-separated model biomembranes containing no charged lipids. Our results provide microscopic insight into the role of membrane rigidity and electrostatics in determining membrane permeation. This can lead to great potential benefits in rational designing of NPs for bioimaging and drug delivery applications as well as in assessing and alleviating cytotoxicity of NPs.

Generalized synthesis of biomolecule-derived and functionalized fluorescent carbon nanoparticle

Abstract: Although wide variety of molecular precursors have been used for carbonization-based synthesis of fluorescent carbon nanoparticle, biomolecule-derived carbon nanoparticle with tunable fluorescence is difficult to synthesize. Here, we report a generalized approach for the preparation of fluorescent carbon nanoparticle from various biomolecules, such as lactose, ascorbic acid, tyrosine and sucrose. The method involves controlled carbonization of molecular precursor in ethylene glycol at 190°C in the presence of Na3PO4. The presented synthetic method can produce 20–30 mg of nanoparticles in one batch with fluorescence quantum yield in the range of 1–10% and nanoparticles can be conjugated with primary amine-terminated chemical/biochemical by simple incubation. These fluorescent carbon nanoparticles can be transformed into different nanobioconjugates for various biomedical applications.