A single-step multi-level supramolecular system for cancer sonotheranostics

A multi-level supramolecular system produced by single-step Fe3+-mediated ionic crosslinking self-assembly can overcome the critical issues of current sonodynamic therapy (SDT) and address the need to monitor therapeutic effects in vivo with a non-invasive approach.

Download Full-text

Dissecting the Structure-Function Relationship of a Fungicidal Peptide Derived from the Constant Region of Human Immunoglobulins

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01753-15 ◽

2016 ◽

Vol 60 (4) ◽

pp. 2435-2442 ◽

Cited By ~ 5

Author(s):

Tecla Ciociola ◽

Thelma A. Pertinhez ◽

Laura Giovati ◽

Martina Sperindè ◽

Walter Magliani ◽

...

Keyword(s):

Self Assembly ◽

Galleria Mellonella ◽

Critical Role ◽

Yeast Cells ◽

Therapeutic Effects ◽

Constant Region ◽

Content Type ◽

Complementarity Determining Regions

ABSTRACTSynthetic peptides encompassing sequences related to the complementarity-determining regions of antibodies or derived from their constant region (Fc peptides) were proven to exert differential antimicrobial, antiviral, antitumor, and/or immunomodulatory activitiesin vitroand/orin vivo, regardless of the specificity and isotype of the parental antibody. Alanine substitution derivatives of these peptides exhibited unaltered, increased, or decreased candidacidal activitiesin vitro. The bioactive IgG-derived Fc N10K peptide (NQVSLTCLVK) spontaneously self-assembles, a feature previously recognized as relevant for the therapeutic activity of another antibody-derived peptide. We evaluated the contribution of each residue to the peptide self-assembling capability by circular-dichroism spectroscopy. The interaction of the N10K peptide and its derivatives withCandida albicanscells was studied by confocal, transmission, and scanning electron microscopy. The apoptosis and autophagy induction profiles in yeast cells treated with the peptides were evaluated by flow cytometry, and the therapeutic efficacy against candidal infection was studied in aGalleria mellonellamodel. Overall, the results indicate a critical role for some residues in the self-assembly process and a correlation of that capability with the candidacidal activities of the peptidesin vitroand their therapeutic effectsin vivo.

Download Full-text

IRONSperm: Sperm-templated soft magnetic microrobots

Science Advances ◽

10.1126/sciadv.aba5855 ◽

2020 ◽

Vol 6 (28) ◽

pp. eaba5855 ◽

Cited By ~ 7

Author(s):

Veronika Magdanz ◽

Islam S. M. Khalil ◽

Juliane Simmchen ◽

Guilherme P. Furtado ◽

Sumit Mohanty ◽

...

Keyword(s):

Self Assembly ◽

Drug Loading ◽

Chemotherapeutic Agents ◽

Single Step ◽

Biological Entity ◽

Sperm Cells ◽

Soft Magnetic ◽

Actuation Frequency ◽

Magnetic Microrobots

We develop biohybrid magnetic microrobots by electrostatic self-assembly of nonmotile sperm cells and magnetic nanoparticles. Incorporating a biological entity into microrobots entails many functional advantages beyond shape templating, such as the facile uptake of chemotherapeutic agents to achieve targeted drug delivery. We present a single-step electrostatic self-assembly technique to fabricate IRONSperms, soft magnetic microswimmers that emulate the motion of motile sperm cells. Our experiments and theoretical predictions show that the swimming speed of IRONSperms exceeds 0.2 body length/s (6.8 ± 4.1 µm/s) at an actuation frequency of 8 Hz and precision angle of 45°. We demonstrate that the nanoparticle coating increases the acoustic impedance of the sperm cells and enables localization of clusters of IRONSperm using ultrasound feedback. We also confirm the biocompatibility and drug loading ability of these microrobots, and their promise as biocompatible, controllable, and detectable biohybrid tools for in vivo targeted therapy.

Download Full-text

IMAGING TECHNIQUES FOR THE EVALUATION OF GRAPES IN WITHERING FOR AMARONE WINE PRODUCTION

Istituto Lombardo - Accademia di Scienze e Lettere - Incontri di Studio ◽

10.4081/incontri.2018.436 ◽

2018 ◽

Author(s):

Barbara Cisterna ◽

Federico Boschi ◽

Anna Cleta Croce ◽

Rachele Podda ◽

Serena Zanzoni ◽

...

Keyword(s):

Optical Properties ◽

Ex Vivo ◽

Imaging Techniques ◽

Wine Production ◽

Invasive Approach ◽

Non Invasive ◽

Innovative Materials ◽

Amarone Wine

Optical Imaging (OI) is an emerging field developed in recent years which can be a very versatile, fast and non-invasive approach for the acquisition of images of small (few centimetres) sized samples, such as layers of cells (in vitro), small animals (in vivo), animal organs (ex vivo) and innovative materials. OI was primarily developed for biomedical applications to study the progression of some pathologies and to assess the efficacy of new pharmaceutical compounds. Here we applied the OI technique to a completely new field: the study of food optical properties. In this case we exploited the optical properties of endogenous molecules, which are generally considered responsible of a background noise affecting the investigation. Here we used this sort of “noise”, named autofluorescence, to obtain information on the drying of Corvinone grapes employed for Amarone wine production. OI can provide interesting information and, inserted in a multimodal approach, it may be a real support to other techniques in the description of a biological phenomenon.

Download Full-text

In vivo measurement of pH and CO2 levels in the uterus of sows through the estrous cycle and after insemination

Scientific Reports ◽

10.1038/s41598-021-82620-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Octavio López-Albors ◽

Pedro José Llamas-López ◽

Joaquín Ángel Ortuño ◽

Rafael Latorre ◽

Francisco Alberto García-Vázquez

Keyword(s):

Estrous Cycle ◽

Assisted Reproductive Technologies ◽

Reproductive Technologies ◽

Invasive Approach ◽

Vitro Fertilization ◽

Non Invasive ◽

Physiological Values

AbstractThe pH–CO2–HCO3− system is a ubiquitous biological regulator with important functional implications for reproduction. Knowledge of the physiological values of its components is relevant for reproductive biology and the optimization of Assisted Reproductive Technologies (ARTs). However, in situ measurements of these parameters in the uterus are scarce or null. This study describes a non-invasive method for in situ time-lapse recording of pH and CO2 within the uterus of non-anesthetized sows. Animals were at three different reproductive conditions, estrous with no insemination and two hours after insemination, and diestrous. From pH and CO2 data, HCO3− concentration was estimated. The non-invasive approach to the porcine uterus with novel optical probes allowed the obtaining of in situ physiological values of pH, CO2, and HCO3−. Variable oscillatory patterns of pH, CO2 and HCO3− were found independently of the estrous condition. Insemination did not immediately change the levels of uterine pH, CO2 (%) and HCO3− concentration, but all the values were affected by the estrous cycle decreasing significantly at diestrous condition. This study contributes to a better understanding of the in vivo regulation of the pH-CO2-HCO3− system in the uterus and may help to optimize the protocols of sperm treatment for in vitro fertilization.

Download Full-text

Foregut organ progenitors and their niche display distinct viscoelastic properties in vivo during early morphogenesis stages

10.1101/2021.05.31.446410 ◽

2021 ◽

Author(s):

Aliaksandr Dzementsei ◽

Younes F. A Barooji ◽

Elke A Ober ◽

Lene Broeng Oddershede

Keyword(s):

Optical Tweezers ◽

Material Properties ◽

Biological Function ◽

Living Matter ◽

Internal Organs ◽

Neighboring Cell ◽

Invasive Approach ◽

Non Invasive

Material properties of living matter play an important role for biological function and development. Yet, quantification of material properties of internal organs in vivo, without causing physiological damage, remains challenging. Here, we present a non-invasive approach based on modified optical tweezers for quantifying sub-cellular material properties deep inside living zebrafish. Material properties of cells within the gut region of living zebrafish are quantified as deep as 150 μ into the biological tissue. The measurements demonstrate differential mechanical properties of the developing foregut organs progenitors: Gut progenitors are more elastic than any of the neighboring cell populations at the time when the developing organs undergo substantial displacements during morphogenesis. The higher elasticity of gut progenitors correlates with an increased cellular concentration of microtubules. The results infer a role of material properties during morphogenesis and the approach paves the way for quantitative material investigations in vivo of embryos, explants, or organoids.

Download Full-text

In vivo measurement of pH, CO2 and HCO3- levels in the uterus of non-anesthetized sows through the estrous cycle and after insemination

10.21203/rs.3.rs-47835/v1 ◽

2020 ◽

Author(s):

Octavio López Albors ◽

Pedro José Llamas-López ◽

Joaquín Ortuño ◽

Rafael Latorre ◽

Francisco Alberto García Vázquez

Keyword(s):

Estrous Cycle ◽

Time Lapse ◽

Invasive Approach ◽

In Vivo Measurement ◽

Non Invasive ◽

Reproductive Techniques ◽

Physiological Values

Abstract Background The pH-CO2-HCO3− system is a ubiquitous biological regulator with important functional implications for reproduction. Knowledge of the physiological values of its components is relevant for reproductive biology and the optimization of Assistant Reproductive Techniques (ARTs). In vivo pH of the oviduct and uterus has been estimated by direct in situ measurements in a few species. However, regarding the levels of CO2 and HCO3−, information is very scarce and, when available, it comes from fluid samples instead of in vivo estimations. This study describes a non-invasive method to measure pH and % of CO2 in the uterus of sows with cutting-edge technology and no medication. Sows were at three different reproductive conditions, estrous with no insemination E(-)AI and after insemination E(+)AI, and diestrous (non-estrous, NE). From pH and CO2 data, HCO3− concentration was estimated. Results The designed methodology allowed for in situ time-lapse recording of pH and % of CO2 within the uterus of non-anesthetized sows. Variable oscillatory patterns of pH, CO2 and HCO3− were found independently of the estrous condition. Insemination did not changed the levels of uterine pH, % of CO2 and HCO3− concentration, -E(-)AI = E(+)AI-, but all the values were affected by the estrous cycle in a way that decreased significantly at diestrous condition - E(-)AI and E(+)AI > NE-. Conclusions A non-invasive approach to the porcine uterus with novel optical probes allowed the obtaining of in situ physiological values of pH, CO2, and HCO3− at different reproductive conditions. While the short-time presence of sperm in the uterus did not change the physiological milieu, the whole pH-CO2-HCO3− system was affected by the estrous cycle. This study contributes to a better understanding of the in vivo regulation of the pH/CO2/HCO3− system in the uterus and may help to optimize the protocols of sperm treatment for in vitro fertilization.

Download Full-text

TMOD-22. AKALUC BIOLUMINESCENCE OFFERS SUPERIOR SENSITIVITY TO TRACK IN VIVO GBM EXPANSION

Neuro-Oncology ◽

10.1093/neuonc/noaa215.972 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii232-ii232

Author(s):

Dominique Bozec ◽

Anirudh Sattiraju ◽

Alexandros Bouras ◽

Joe Gerald Jesu Raj ◽

Daniel Rivera ◽

...

Keyword(s):

High Sensitivity ◽

Current Method ◽

Firefly Luciferase ◽

Brain Parenchyma ◽

Therapeutic Effects ◽

Non Invasive ◽

Longitudinal Tracking ◽

Cancer Studies

Abstract Longitudinal tracking of tumor growth using non-invasive bioluminescence imaging (BLI) is a key approach for in vivo cancer studies, but the current method of firefly luciferase (Fluc) BLI has quantitative limitations, as it is only suited for detection of tumors of considerable sizes at advanced stage, typically in the order of >105 cells. Recently, Akaluciferase (Akaluc) has been developed as an alternative BLI system that offers higher signal strength and better light penetration of tissue due to its red-shifted emission. Here, we established Akaluc BLI as a new sensitive method for in vivo tracking of glioblastoma (GBM) expansion in intracranial transplant models. In multiple GBM cell lines, including the frequently used U87MG and GL261, as well as patient-derived glioma stem cells (GSC), we demonstrate that Akaluc-expressing GBM cells produced more than 50-times brighter BLI signals in vitro and up to 100-fold higher signal intensities in vivo over Fluc-expressing counterparts. The higher sensitivity of Akaluc BLI permits early in vivo detection of intracranial GBM transplants starting as early as 4 hours after implantation and with as little as 5,000 transplanted GSC. We also reveal a prolonged engraftment period in intracranial GSC transplants before wide dissemination into host brain parenchyma. Akaluc BLI is also advantageous for longitudinal monitoring of therapeutic effects of chemoradiation for GBM and detection of early phase of tumor relapse. Thus, Akaluc BLI offers an important addition to the tool box for cancer research. SIGNIFICANCE: The high sensitivity of Akaluc bioluminescence is a significant improvement for the non-invasive tracking of tumors in preclinical cancer studies, including detection of small incipient tumors and micro-metastasis.

Download Full-text

P4490Safety and feasibility of non invasive transthoracic pulsed cavitational ultrasound therapy (PCUT) on a swine aortic valve model

European Heart Journal ◽

10.1093/eurheartj/ehz745.0883 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

E Messas ◽

M Remond ◽

G Goudot ◽

R Penot ◽

D Ladarre ◽

...

Keyword(s):

Side Effects ◽

Aortic Valve ◽

High Power ◽

Ultrasound Therapy ◽

Antithrombotic Treatment ◽

Invasive Approach ◽

Non Invasive ◽

Valve Model

Abstract Background Aortic valve stenosis is associated with age and comorbidities, which require exploring less invasive therapeutic approach to improve patient outcome. We previously demonstrated in vitro and in vivo that pulsed cavitational ultrasound therapy (PCUT) can improve calcified bioprosthesis stenosis by softening leaflets remotely. To apply this technique noninvasively we aim to test PCUT transthoracicalyin a swine model targeting aortic valve. Because calcified aortic valve model doesn't exist, we tested this technique on a normal valve. Objective Primary objective was to estimate the feasibility and safety of PCUT. Secondary objectiveswere to evaluate occurrence, severity and evolution of cardiovascular side effects during therapy and within follow-up period (30±5 days) with and without double antithrombotic treatment. Methods All the experiments were performed on normal aortic valves (n=19) of swine. The system was composed of a high-power multi-element transducer with electronic steering and 2D echocardiographic probe embedded in the center. Swine were divided in three groups: one with PCUT and no anti thrombotic treatment (n=10), a second with PCUT and one-month treatment of aspirin and clopidogrel (n=5) and third group sham (n=4). All groups were followed up after 30 days. Results The primary feasibility endpoint was successful in 100% of tests performed (n=16). A maximal amplitude of 70 MPa and −19 MPa respectively for positive and negative peak pressure was found at the focus point. Survival at 30 days was 100% and no life-threatening arrhythmia was recorded and no sustained ventricular arrhythmia (SVT >30 s) was noticed. For the secondary safety objectives,we recorded acutely, at the time of procedure, NSVT in 7 pigs which corresponded to a cumulated duration of 2.1 out of the 485.3 min of the total US delivery (0.4% of time). Mean cycle of NSVT was slow 428.9 ms in average (139.6 bpm). The interruption or decrease of power of US delivery allowed immediate cessation of cardiac arrhythmia in all cases. There was no evidence of damage to the valve and no observation of impairment of valvular function by echocardiography. Only one animal showed side effects (RV dilatation) and the RV returned to normal after cessation of the therapy with no sequelae at follow up. At follow up no significant findings biology disturbance or valve thrombosis was observed (creatinine, CK MB, hemoglobin, hematocrit, haptoglobin or red blood cell numbers). Antithrombotic treatment didn't demonstrate any advantage at follow up. Conclusion We demonstrated in vivo feasibility and safety of transthoracic PCUT targeting aortic valve without any serious adverse event and no significant histopathology damage. We hope that this first-time transthoracic delivery of very focused ultrasound at high power will pave the way to new non invasive approach of valve softening in case of human aortic valve calcified stenosis.

Download Full-text

In Vivo, Non Invasive Evaluation of the Self Assembly of Unfolding Proteins in Transparent Lens Cells

The FASEB Journal ◽

10.1096/fasebj.24.1_supplement.684.4 ◽

2010 ◽

Vol 24 (S1) ◽

Author(s):

John I Clark ◽

Ernest Arnett ◽

Judy M Clark ◽

Teri M Greiling

Keyword(s):

Self Assembly ◽

The Self ◽

Non Invasive ◽

Lens Cells ◽

Invasive Evaluation

Download Full-text

A Single-Step Self-Assembly Approach for the Fabrication of Aligned and Multilayered Three-Dimensional Tissue Constructs Using Multidomain Peptide Hydrogel

SLAS TECHNOLOGY Translating Life Sciences Innovation ◽

10.1177/2472630318777759 ◽

2018 ◽

Vol 24 (1) ◽

pp. 55-65 ◽

Cited By ~ 1

Author(s):

Yinshen Wee ◽

Amanda N. Moore ◽

Shihai Jia ◽

Jing Zhou ◽

John S. Colombo ◽

...

Keyword(s):

Self Assembly ◽

Expression Profiles ◽

Three Dimensional ◽

Gene Expression Profiles ◽

Structural Features ◽

Single Step ◽

Volume Percentage ◽

Ecm Remodeling ◽

Tissue Constructs

Hydrogels are homogenous materials that are limited in their ability to form oriented multilayered architecture in three-dimensional (3D) tissue constructs. Current techniques have led to advancements in this area. Such techniques often require extra devices and/or involve complex processes that are inaccessible to many laboratories. Here is described a one-step methodology that permits reliable alignment of cells into multiple layers using a self-assembling multidomain peptide (MDP) hydrogels. We characterized the structural features, viability, and molecular properties of dental pulp cells fabricated with MDP and demonstrated that manipulation of the layering of cells in the scaffolds was achieved by decreasing the weight by volume percentage (w/v%) of MDP contained within the scaffold. This approach allows cells to remodel their environment and enhanced various gene expression profiles, such as cell proliferation, angiogenesis, and extracellular matrix (ECM) remodeling-related genes. We further validated our approach for constructing various architectural configurations of tissues by fabricating cells into stratified multilayered and tubular structures. Our methodology provides a simple, rapid way to generate 3D tissue constructs with multilayered architectures. This method shows great potential to mimic in vivo microenvironments for cells and may be of benefit in modeling more complex tissues in the field of regenerative medicine.

Download Full-text