More than 60 years ago, the effect whereby radiotherapy at one site may lead to regression of metastatic cancer at distant sites that are not irradiated was described and called the abscopal effect (from 'ab scopus', that is, away from the target). The abscopal effect has been connected to mechanisms involving the immune system. However, the effect is rare because at the time of treatment, established immune-tolerance mechanisms may hamper the development of sufficiently robust abscopal responses. Today, the growing consensus is that combining radiotherapy with immunotherapy provides an opportunity to boost abscopal response rates, extending the use of radiotherapy to treatment of both local and metastatic disease. In this Opinion article, we review evidence for this growing consensus and highlight emerging limitations to boosting the abscopal effect using immunotherapy. This is followed by a perspective on current and potential cross-disciplinary approaches, including the use of smart materials to address these limitations.

Using immunotherapy to boost the abscopal effect

Cancer immunotherapy is revolutionizing oncology. However, dose-limiting toxicities and low patient response rates remain major challenges in the clinic. Cancer nanomedicine in combination with immunotherapies offers the possibility to amplify antitumour immune responses and to sensitize tumours to immunotherapies in a safe and effective manner. In this Review, we discuss opportunities for combination immunotherapy based on nanoparticle platforms designed for chemotherapy, photothermal therapy, photodynamic therapy, radiotherapy and gene therapy. We highlight how nanoparticles can be used to reprogramme the immunosuppressive tumour microenvironment and to trigger systemic antitumour immunity, synergizing with immunotherapies against advanced cancer. Finally, we discuss strategies to improve tumour and immune cell targeting while minimizing toxicity and immune-related adverse events, and we explore the potential of theranostic nanoparticles for combination immunotherapy. Cancer nanomedicine in combination with immunotherapies offers the possibility to amplify antitumour immune responses and to sensitize tumours to immunotherapies. In this Review, the authors discuss combination immunotherapy based on nanoparticle platforms designed for chemotherapy, photothermal therapy, photodynamic therapy, radiotherapy and gene therapy.

Cancer nanomedicine for combination cancer immunotherapy

The unique properties of gold nanoparticles, their rich surface chemistry, and low toxicity as well as easy methods of synthesis have promoted conjugation of the particles with numerous biomolecules for site-specific delivery. Gold nanoparticles have multiple applications including photoablation, diagnostic imaging, radiosensitization, vaccine development, antioxidant, and multifunctional drug-delivery vehicles. These applications require an increasingly complex level of surface decoration in order to achieve efficacy, and limit off-target toxicity. This review will discuss the chemical and physical approaches commonly utilized in relation to surface decoration and the powerful system used to indicate success of the conjugation. Finally, we review the range of recent studies about covalent and noncovalent modes for conjugation of antibodies to the particle surface that aim to advance gold nanoparticle treatments and diagnostics toward the clinic.

Various methods of gold nanoparticles (GNPs) conjugation to antibodies

Green preparation of carbon dots with papaya as carbon source for effective fluorescent sensing of Iron (III) and Escherichia coli.

Exosomes are emerging as effective therapeutic tools for various pathologies These extracellular vesicles can bypass biological barriers, including the blood-brain barrier, and can serve as powerful drug and gene therapy transporters However, the progress of therapy development is impeded by several challenges, including insufficient data on exosome trafficking and biodistribution and the difficulty to image deep brain structures in vivo Herein, we established a method for noninvasive in vivo neuroimaging and tracking of exosomes, based on glucose-coated gold nanoparticle (GNP) labeling and computed tomography imaging Labeling of exosomes with the GNPs was achieved directly, as opposed to the typical and less efficient indirect labeling mode through parent cells On the mechanistic level, we found that the glucose-coated GNPs were uptaken into MSC-derived exosomes via an active, energy-dependent mechanism that is mediated by the glucose transporter GLUT-1 and involves endocytic proteins Next, we dete

In Vivo Neuroimaging of Exosomes Using Gold Nanoparticles

Application of immune cell-based therapy in routine clinical practice is challenging due to the poorly understood mechanisms underlying success or failure of treatment. Development of accurate and quantitative imaging techniques for noninvasive cell tracking can provide essential knowledge for elucidating these mechanisms. We designed a novel method for longitudinal and quantitative in vivo cell tracking, based on the superior visualization abilities of classical X-ray computed tomography (CT), combined with state-of-the-art nanotechnology. Herein, T-cells were transduced to express a melanoma-specific T-cell receptor and then labeled with gold nanoparticles (GNPs) as a CT contrast agent. The GNP-labeled T-cells were injected intravenously to mice bearing human melanoma xenografts, and whole-body CT imaging allowed examination of the distribution, migration, and kinetics of T-cells. Using CT, we found that transduced T-cells accumulated at the tumor site, as opposed to nontransduced cells. Labeling with g...

Nanomedicine for Cancer Immunotherapy: Tracking Cancer-Specific T-Cells in Vivo with Gold Nanoparticles and CT Imaging

https://www.fertstert.org/article/S0015-0282(07)00234-8/pdf

Is fine morphology of the human sperm nuclei affected by in vitro incubation at 37°C?

Nerve growth factor (NGF) plays a vital role in reducing the loss of cholinergic neurons in Alzheimer's disease (AD). However, its delivery to the brain remains a challenge. Herein, NGF is loaded into degradable oxidized porous silicon (PSiO2 ) carriers, which are designed to carry and continuously release the protein over a 1 month period. The released NGF exhibits a substantial neuroprotective effect in differentiated rat pheochromocytoma PC12 cells against amyloid-beta (Aβ)-induced cytotoxicity, which is associated with Alzheimer's disease. Next, two potential localized administration routes of the porous carriers into murine brain are investigated: implantation of PSiO2 chips above the dura mater, and biolistic bombardment of PSiO2 microparticles through an opening in the skull using a pneumatic gene gun. The PSiO2 -implanted mice are monitored for a period of 8 weeks and no inflammation or adverse effects are observed. Subsequently, a successful biolistic delivery of these highly porous microparticles into a live-mouse brain is demonstrated for the first time. The bombarded microparticles are observed to penetrate the brain and reach a depth of 150 µm. These results pave the way for using degradable PSiO2 carriers as potential localized delivery systems for NGF to the brain.

Neuroprotective Effect of Nerve Growth Factor Loaded in Porous Silicon Nanostructures in an Alzheimer's Disease Model and Potential Delivery to the Brain.

Campylobacter fetus subsp. fetus infection can occur in female sheep, causing infertility or abortion. Despite extensive research on the effect of these bacteria on female fertility, little research has been done on the influence of C. fetus subsp. fetus on the male factor. Our objective was to examine the influence of C. fetus subsp. fetus on ram sperm. Motility index, percentage of live spermatozoa, mean alphat value (an indication of the chromatin stability of the sperm cell) and percentage of sperm cells expressing the FAS receptor were measured in sperm incubated in the presence or absence of C. fetus subsp. fetus. The motility index and viability of sperm incubated with the bacteria were lower than those of untreated sperm samples after 5 h. In bacteria-incubated sperm cells, the percentage expressing FAS receptor was already significantly elevated at 15 min. Bacteria-incubated sperm showed a greater prevalence of morphological damage. The bacteria were attached to tail and acrosome regions, and the sperm damage was concentrated in both the motility and chromatin regions. Bacteria-infected sperm cells showed a decrease in motility, increase in early acrosome reaction and chromatin damage. Similar effects were induced by incubation of the sperm with supernatants from C. fetus subsp. fetus cultures. Thus this study demonstrates that C. fetus subsp. fetus has a detrimental effect on the quality of ram sperm.

Influence of Campylobacter fetus subsp. fetus on ram sperm cell quality.

The invention provides pharmaceutical compositions for treating male sub-fertility including an agent that causes a reduction in an effect of extracellular DNA on sperm cells. The agent may be, for example, an enzyme that degrades DNA such as DNase, a substance that blocks the interaction between cell free DNA and sperm cell surface receptors, a substance that binds to DNA, a substance that inhibits endogenous sperm cell DNase, a substance that inhibits a member of a signal transduction pathway mediated by DNA binding to sperm cell surface receptors, or an agent that stimulates production of an endogenous substance that causes a reduction in an antifertility effect of cell free DNA on sperm cells. The invention also provides methods for treating male sub-fertility comprising administering a pharmaceutical composition of the invention. The invention further provides methods for determining a fertility status in a male subject, methods for assisted reproduction, methods for selecting an assisted reproduction technique (ART), and methods for selecting sperm cells in a sperm cell population for use in an assisted reproduction technique.

Ronen Yehuda

Papers

Nanomedicine for Cancer Immunotherapy: Tracking Cancer-Specific T-Cells in Vivo with Gold Nanoparticles and CT Imaging

Is fine morphology of the human sperm nuclei affected by in vitro incubation at 37°C?

Neuroprotective Effect of Nerve Growth Factor Loaded in Porous Silicon Nanostructures in an Alzheimer's Disease Model and Potential Delivery to the Brain.

Influence of Campylobacter fetus subsp. fetus on ram sperm cell quality.

Method and pharmacological composition for the diagnosis and treatment of male sub-fertility