Carbon-Based Nanomaterials for Delivery of Biologicals and Therapeutics: A Cutting-Edge Technology

After hydrogen and oxygen, carbon is the third most abundant component present in the cosmos with excellent characteristic features of binding to itself and nearly all elements. Since ancient times, carbon-based materials such as graphite, charcoal, and carbon black have been utilized for writing and drawing materials. As these materials possess excellent chemical, mechanical, electrical, and thermal features, they have been readily engineered into carbon-based nanomaterials (CNMs) such as carbon nanotubes, graphene oxide, graphene quantum dots, nanodiamonds, fullerenes, carbon nano-onions, and so forth. These materials are now widely explored in biomedical applications. Thus, the emergence of CNMs has opened up a gateway for the detection, delivery, and treatment of a multitude of diseases. They are being actively researched for applications within tissue engineering, as vaccine vectors, and for the delivery of therapeutics to the immune system. This review focuses on the recent advances in various types of CNMs, their fabrication techniques, and their application in the delivery of therapeutics both in vitro and in vivo. The review also focuses on the toxicity concern of the CNMs and the possible remedies to tackle the toxicity issues. Concluding remarks emphasize all the CNMs discussed in the review over their possible biomedical applications, while the future perspectives section discusses the approaches to bring CNMs into the mainstream of clinical trials and their therapeutic applications.

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Sialyltransferase Inhibitors for the Treatment of Cancer Metastasis: Current Challenges and Future Perspectives

Molecules ◽

10.3390/molecules26185673 ◽

2021 ◽

Vol 26 (18) ◽

pp. 5673

Author(s):

Ser John Lynon P. Perez ◽

Chih-Wei Fu ◽

Wen-Shan Li

Keyword(s):

Biomedical Applications ◽

Cancer Metastasis ◽

Future Perspectives ◽

The Past ◽

Cell Metastasis ◽

Tumor Cell Metastasis ◽

In Vivo Effects ◽

Subtype Selective

Potent, cell-permeable, and subtype-selective sialyltransferase inhibitors represent an attractive family of substances that can potentially be used for the clinical treatment of cancer metastasis. These substances operate by specifically inhibiting sialyltransferase-mediated hypersialylation of cell surface glycoproteins or glycolipids, which then blocks the sialic acid recognition pathway and leads to deterioration of cell motility and invasion. A vast amount of evidence for the in vitro and in vivo effects of sialyltransferase inhibition or knockdown on tumor progression and tumor cell metastasis or colonization has been accumulated over the past decades. In this regard, this review comprehensively discusses the results of studies that have led to the recent discovery and development of sialyltransferase inhibitors, their potential biomedical applications in the treatment of cancer metastasis, and their current limitations and future opportunities.

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Proinflammatory Effect of Carbon-Based Nanomaterials: In Vitro Study on Stimulation of Inflammasome NLRP3 via Destabilisation of Lysosomes

Nanomaterials ◽

10.3390/nano10030418 ◽

2020 ◽

Vol 10 (3) ◽

pp. 418 ◽

Cited By ~ 3

Author(s):

Tereza Svadlakova ◽

Frantisek Hubatka ◽

Pavlina Turanek Knotigova ◽

Pavel Kulich ◽

Josef Masek ◽

...

Keyword(s):

Muramyl Dipeptide ◽

In Vitro Study ◽

Blood Monocytes ◽

Alternative Pathways ◽

Direct Activation ◽

Graphene Derivatives ◽

Carbon Based Nanomaterials ◽

Carbon Based

Carbon-based nanomaterials (C-BNM) have recently attracted an increased attention as the materials with potential applications in industry and medicine. Bioresistance and proinflammatory potential of C-BNM is the main obstacle for their medicinal application which was documented in vivo and in vitro. However, there are still limited data especially on graphene derivatives such as graphene platelets (GP). In this work, we compared multi-walled carbon nanotubes (MWCNT) and two different types of pristine GP in their potential to activate inflammasome NLRP3 (The nod-like receptor family pyrin domain containing 3) in vitro. Our study is focused on exposure of THP-1/THP1-null cells and peripheral blood monocytes to C-BNM as representative models of canonical and alternative pathways, respectively. Although all nanomaterials were extensively accumulated in the cytoplasm, increasing doses of all C-BNM did not lead to cell death. We observed direct activation of NLRP3 via destabilization of lysosomes and release of cathepsin B into cytoplasm only in the case of MWCNTs. Direct activation of NLRP3 by both GP was statistically insignificant but could be induced by synergic action with muramyl dipeptide (MDP), as a representative molecule of the family of pathogen-associated molecular patterns (PAMPs). This study demonstrates a possible proinflammatory potential of GP and MWCNT acting through NLRP3 activation.

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Biological and biomedical applications of collagenous biomaterials

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100161849 ◽

1990 ◽

Vol 48 (3) ◽

pp. 856-857

Author(s):

Yasushi P. Kato ◽

Michael G. Dunn ◽

Frederick H. Silver ◽

Arthur J. Wasserman

Keyword(s):

Biomedical Applications ◽

Soft Tissues ◽

Collagen Fibers ◽

Bone Collagen ◽

Cover Slip ◽

Fibroblast Migration ◽

Cellular Expression ◽

Defect Repair

Collagenous biomaterials have been used for growing cells in vitro as well as for augmentation and replacement of hard and soft tissues. The substratum used for culturing cells is implicated in the modulation of phenotypic cellular expression, cellular orientation and adhesion. Collagen may have a strong influence on these cellular parameters when used as a substrate in vitro. Clinically, collagen has many applications to wound healing including, skin and bone substitution, tendon, ligament, and nerve replacement. In this report we demonstrate two uses of collagen. First as a fiber to support fibroblast growth in vitro, and second as a demineralized bone/collagen sponge for radial bone defect repair in vivo.For the in vitro study, collagen fibers were prepared as described previously. Primary rat tendon fibroblasts (1° RTF) were isolated and cultured for 5 days on 1 X 15 mm sterile cover slips. Six to seven collagen fibers, were glued parallel to each other onto a circular cover slip (D=18mm) and the 1 X 15mm cover slip populated with 1° RTF was placed at the center perpendicular to the collagen fibers. Fibroblast migration from the 1 x 15mm cover slip onto and along the collagen fibers was measured daily using a phase contrast microscope (Olympus CK-2) with a calibrated eyepiece. Migratory rates for fibroblasts were determined from 36 fibers over 4 days.

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Conjugates of Classical DNA/RNA Binder with Nucleobase: Chemical, Biochemical and Biomedical Applications

Current Medicinal Chemistry ◽

10.2174/0929867325666180508090640 ◽

2019 ◽

Vol 26 (30) ◽

pp. 5609-5624

Author(s):

Dijana Saftić ◽

Željka Ban ◽

Josipa Matić ◽

Lidija-Marija Tumirv ◽

Ivo Piantanida

Keyword(s):

Molecular Weight ◽

Small Molecules ◽

Biomedical Applications ◽

Protein Targets ◽

New Class ◽

Rna Targets ◽

Covalently Linked ◽

Structural Aspects

: Among the most intensively studied classes of small molecules (molecular weight < 650) in biomedical research are small molecules that non-covalently bind to DNA/RNA, and another intensively studied class is nucleobase derivatives. Both classes have been intensively elaborated in many books and reviews. However, conjugates consisting of DNA/RNA binder covalently linked to nucleobase are much less studied and have not been reviewed in the last two decades. Therefore, this review summarized reports on the design of classical DNA/RNA binder – nucleobase conjugates, as well as data about their interactions with various DNA or RNA targets, and even in some cases protein targets are involved. According to these data, the most important structural aspects of selective or even specific recognition between small molecule and target are proposed, and where possible related biochemical and biomedical aspects were discussed. The general conclusion is that this, rather new class of molecules showed an amazing set of recognition tools for numerous DNA or RNA targets in the last two decades, as well as few intriguing in vitro and in vivo selectivities. Several lead research lines show promising advancements toward either novel, highly selective markers or bioactive, potentially druggable molecules.

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Hexapod Assassins’ Potion: Venom Composition and Bioactivity from the Eurasian Assassin Bug Rhynocoris iracundus

Biomedicines ◽

10.3390/biomedicines9070819 ◽

2021 ◽

Vol 9 (7) ◽

pp. 819

Author(s):

Nicolai Rügen ◽

Timothy P. Jenkins ◽

Natalie Wielsch ◽

Heiko Vogel ◽

Benjamin-Florian Hempel ◽

...

Keyword(s):

Biomedical Applications ◽

Galleria Mellonella ◽

Systemic Reactions ◽

Venom Composition ◽

Assassin Bug ◽

Molecular Components ◽

First Time ◽

Tissue Digestion

Assassin bug venoms are potent and exert diverse biological functions, making them potential biomedical goldmines. Besides feeding functions on arthropods, assassin bugs also use their venom for defense purposes causing localized and systemic reactions in vertebrates. However, assassin bug venoms remain poorly characterized. We collected the venom from the assassin bug Rhynocoris iracundus and investigated its composition and bioactivity in vitro and in vivo. It caused lysis of murine neuroblastoma, hepatoma cells, and healthy murine myoblasts. We demonstrated, for the first time, that assassin bug venom induces neurolysis and suggest that it counteracts paralysis locally via the destruction of neural networks, contributing to tissue digestion. Furthermore, the venom caused paralysis and melanization of Galleria mellonella larvae and pupae, whilst also possessing specific antibacterial activity against Escherichia coli, but not Listeria grayi and Pseudomonas aeruginosa. A combinatorial proteo-transcriptomic approach was performed to identify potential toxins responsible for the observed effects. We identified neurotoxic Ptu1, an inhibitory cystin knot (ICK) toxin homologous to ω-conotoxins from cone snails, cytolytic redulysins homologous to trialysins from hematophagous kissing bugs, and pore-forming hemolysins. Additionally, chitinases and kininogens were found and may be responsible for insecticidal and cytolytic activities. We demonstrate the multifunctionality and complexity of assassin bug venom, which renders its molecular components interesting for potential biomedical applications.

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Interfacing cells with organic transistors: a review of in vitro and in vivo applications

Lab on a Chip ◽

10.1039/d0lc01007c ◽

2021 ◽

Vol 21 (5) ◽

pp. 795-820

Author(s):

Andrea Spanu ◽

Laura Martines ◽

Annalisa Bonfiglio

Keyword(s):

Organic Transistors ◽

Future Perspectives ◽

The Past ◽

The Future

This review focuses on the applications of organic transistors in cellular interfacing. It offers a comprehensive retrospective of the past, an overview of the latest innovations, and a glance on the future perspectives of this fast-evolving field.

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Synthesis, Characterization and Evaluation of Peptide Nanostructures for Biomedical Applications

Molecules ◽

10.3390/molecules26154587 ◽

2021 ◽

Vol 26 (15) ◽

pp. 4587

Author(s):

Fanny d’Orlyé ◽

Laura Trapiella-Alfonso ◽

Camille Lescot ◽

Marie Pinvidic ◽

Bich-Thuy Doan ◽

...

Keyword(s):

Amino Acids ◽

Biomedical Applications ◽

Chemical Reactivity ◽

Physical Stability ◽

Chemical Properties ◽

Building Blocks ◽

Imaging Probes ◽

Therapeutic Molecules

There is a challenging need for the development of new alternative nanostructures that can allow the coupling and/or encapsulation of therapeutic/diagnostic molecules while reducing their toxicity and improving their circulation and in-vivo targeting. Among the new materials using natural building blocks, peptides have attracted significant interest because of their simple structure, relative chemical and physical stability, diversity of sequences and forms, their easy functionalization with (bio)molecules and the possibility of synthesizing them in large quantities. A number of them have the ability to self-assemble into nanotubes, -spheres, -vesicles or -rods under mild conditions, which opens up new applications in biology and nanomedicine due to their intrinsic biocompatibility and biodegradability as well as their surface chemical reactivity via amino- and carboxyl groups. In order to obtain nanostructures suitable for biomedical applications, the structure, size, shape and surface chemistry of these nanoplatforms must be optimized. These properties depend directly on the nature and sequence of the amino acids that constitute them. It is therefore essential to control the order in which the amino acids are introduced during the synthesis of short peptide chains and to evaluate their in-vitro and in-vivo physico-chemical properties before testing them for biomedical applications. This review therefore focuses on the synthesis, functionalization and characterization of peptide sequences that can self-assemble to form nanostructures. The synthesis in batch or with new continuous flow and microflow techniques will be described and compared in terms of amino acids sequence, purification processes, functionalization or encapsulation of targeting ligands, imaging probes as well as therapeutic molecules. Their chemical and biological characterization will be presented to evaluate their purity, toxicity, biocompatibility and biodistribution, and some therapeutic properties in vitro and in vivo. Finally, their main applications in the biomedical field will be presented so as to highlight their importance and advantages over classical nanostructures.

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Antimicrobial Activity of Curcumin in Nanoformulations: A Comprehensive Review

International Journal of Molecular Sciences ◽

10.3390/ijms22137130 ◽

2021 ◽

Vol 22 (13) ◽

pp. 7130

Author(s):

Jeffersson Krishan Trigo-Gutierrez ◽

Yuliana Vega-Chacón ◽

Amanda Brandão Soares ◽

Ewerton Garcia de Oliveira Mima

Keyword(s):

Polymeric Nanoparticles ◽

Graphene Quantum Dots ◽

Antimicrobial Properties ◽

Antimicrobial Effect ◽

Clinical Scenarios ◽

Low Cytotoxicity ◽

Bacteria And Fungi ◽

Drug Resistant Strains

Curcumin (CUR) is a natural substance extracted from turmeric that has antimicrobial properties. Due to its ability to absorb light in the blue spectrum, CUR is also used as a photosensitizer (PS) in antimicrobial Photodynamic Therapy (aPDT). However, CUR is hydrophobic, unstable in solutions, and has low bioavailability, which hinders its clinical use. To circumvent these drawbacks, drug delivery systems (DDSs) have been used. In this review, we summarize the DDSs used to carry CUR and their antimicrobial effect against viruses, bacteria, and fungi, including drug-resistant strains and emergent pathogens such as SARS-CoV-2. The reviewed DDSs include colloidal (micelles, liposomes, nanoemulsions, cyclodextrins, chitosan, and other polymeric nanoparticles), metallic, and mesoporous particles, as well as graphene, quantum dots, and hybrid nanosystems such as films and hydrogels. Free (non-encapsulated) CUR and CUR loaded in DDSs have a broad-spectrum antimicrobial action when used alone or as a PS in aPDT. They also show low cytotoxicity, in vivo biocompatibility, and improved wound healing. Although there are several in vitro and some in vivo investigations describing the nanotechnological aspects and the potential antimicrobial application of CUR-loaded DDSs, clinical trials are not reported and further studies should translate this evidence to the clinical scenarios of infections.

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Injectable non-leaching tissue-mimetic bottlebrush elastomers as an advanced platform for reconstructive surgery

Nature Communications ◽

10.1038/s41467-021-23962-8 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Erfan Dashtimoghadam ◽

Farahnaz Fahimipour ◽

Andrew N. Keith ◽

Foad Vashahi ◽

Pavel Popryadukhin ◽

...

Keyword(s):

Mechanical Properties ◽

Reconstructive Surgery ◽

Biomedical Applications ◽

The Body ◽

Surrounding Tissue ◽

Curing Time ◽

Materials Used ◽

Significant Health

AbstractCurrent materials used in biomedical devices do not match tissue’s mechanical properties and leach various chemicals into the body. These deficiencies pose significant health risks that are further exacerbated by invasive implantation procedures. Herein, we leverage the brush-like polymer architecture to design and administer minimally invasive injectable elastomers that cure in vivo into leachable-free implants with mechanical properties matching the surrounding tissue. This strategy allows tuning curing time from minutes to hours, which empowers a broad range of biomedical applications from rapid wound sealing to time-intensive reconstructive surgery. These injectable elastomers support in vitro cell proliferation, while also demonstrating in vivo implant integrity with a mild inflammatory response and minimal fibrotic encapsulation.

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A Tumbling Magnetic Microrobot System for Biomedical Applications

Micromachines ◽

10.3390/mi11090861 ◽

2020 ◽

Vol 11 (9) ◽

pp. 861

Author(s):

Elizabeth E. Niedert ◽

Chenghao Bi ◽

Georges Adam ◽

Elly Lambert ◽

Luis Solorio ◽

...

Keyword(s):

Ultrasound Imaging ◽

Biomedical Applications ◽

Imaging System ◽

Ex Vivo ◽

Negative Control ◽

Circular Path ◽

Rotational Axis ◽

Significant Difference

A microrobot system comprising an untethered tumbling magnetic microrobot, a two-degree-of-freedom rotating permanent magnet, and an ultrasound imaging system has been developed for in vitro and in vivo biomedical applications. The microrobot tumbles end-over-end in a net forward motion due to applied magnetic torque from the rotating magnet. By turning the rotational axis of the magnet, two-dimensional directional control is possible and the microrobot was steered along various trajectories, including a circular path and P-shaped path. The microrobot is capable of moving over the unstructured terrain within a murine colon in in vitro, in situ, and in vivo conditions, as well as a porcine colon in ex vivo conditions. High-frequency ultrasound imaging allows for real-time determination of the microrobot’s position while it is optically occluded by animal tissue. When coated with a fluorescein payload, the microrobot was shown to release the majority of the payload over a 1-h time period in phosphate-buffered saline. Cytotoxicity tests demonstrated that the microrobot’s constituent materials, SU-8 and polydimethylsiloxane (PDMS), did not show a statistically significant difference in toxicity to murine fibroblasts from the negative control, even when the materials were doped with magnetic neodymium microparticles. The microrobot system’s capabilities make it promising for targeted drug delivery and other in vivo biomedical applications.

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