The engineering of future generations of nanodelivery systems aims at the creation of multifunctional vectors endowed with improved circulation, enhanced targeting and responsiveness to the ...biological environment. Moving past purely bio-inert systems, researchers have begun to create nanoparticles capable of proactively interacting with the biology of the body. Nature offers a wide-range of sources of inspiration for the synthesis of more effective drug delivery platforms. Because the nano-bio-interface is the key driver of nanoparticle behavior and function, the modification of nanoparticles’ surfaces allows the transfer of biological properties to synthetic carriers by imparting them with a biological identity. Modulation of these surface characteristics governs nanoparticle interactions with the biological barriers they encounter. Building off these observations, we provide here an overview of virus- and cell-derived biomimetic delivery systems that combine the intrinsic hallmarks of biological membranes with the delivery capabilities of synthetic carriers. We describe the features and properties of biomimetic delivery systems, recapitulating the distinctive traits and functions of viruses, exosomes, platelets, red and white blood cells. By mimicking these biological entities, we will learn how to more efficiently interact with the human body and refine our ability to negotiate with the biological barriers that impair the therapeutic efficacy of nanoparticles.
In a perfect sequence of events, nanoparticles (NPs) are injected into the bloodstream where they circulate until they reach the target tissue. The ligand on the NP surface recognizes its specific ...receptor expressed on the target tissue and the drug is released in a controlled manner. However, once injected in a physiological environment, NPs interact with biological components and are surrounded by a protein corona (PC). This can trigger an immune response and affect NP toxicity and targeting capabilities. In this review, we provide a survey of recent findings on the NP-PC interactions and discuss how the PC can be used to modulate both cytotoxicity and the immune response as well as to improve the efficacy of targeted delivery of nanocarriers.
Brain tumors are characterized by very high mortality and, despite the continuous research on new pharmacological interventions, little therapeutic progress has been made. One of the main obstacles ...to improve current treatments is represented by the impermeability of the blood vessels residing within nervous tissue as well as of the new vascular net generating from the tumor, commonly referred to as blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB), respectively. In this review, we focused on established and emerging strategies to overcome the blood-brain barrier to increase drug delivery for brain cancer. To date, there are three broad strategies being investigated to cross the brain vascular wall and they are conceived to breach, bypass, and negotiate the access to the nervous tissue. In this paper, we summarized these approaches highlighting their working mechanism and their potential impact on the quality of life of the patients as well as their current status of development.
Tumor extracellular matrix (ECM) represents a major obstacle to the diffusion of therapeutics and drug delivery systems in cancer parenchyma. This biological barrier limits the efficacy of promising ...therapeutic approaches including the delivery of siRNA or agents intended for thermoablation. After extravasation due to the enhanced penetration and retention effect of tumor vasculature, typical nanotherapeutics are unable to reach the nonvascularized and anoxic regions deep within cancer parenchyma. Here, we developed a simple method to provide mesoporous silica nanoparticles (MSN) with a proteolytic surface. To this extent, we chose to conjugate MSN to Bromelain (Br–MSN), a crude enzymatic complex, purified from pineapple stems, that belongs to the peptidase papain family. This surface modification increased particle uptake in endothelial, macrophage, and cancer cell lines with minimal impact on cellular viability. Most importantly Br–MSN showed an increased ability to digest and diffuse in tumor ECM in vitro and in vivo.
Spontaneous preterm birth (PTB) complicates about 12% of pregnancies worldwide, remaining the main cause of neonatal morbidity and mortality. Spontaneous preterm birth PTBs is often caused by ...microbial-induced preterm labor, mediated by an inflammatory process threatening both maternal and newborn health. In search for novel predictive biomarkers of PTB and preterm prelabor rupture of the membranes (pPROM), and to improve understanding of infection related PTB, we performed an untargeted mass spectrometry discovery study on 51 bioptic mid zone amnion samples from premature babies. A total of 6352 proteins were identified. Bioinformatics analyses revealed a ranked core of 159 proteins maximizing the discrimination between the selected clinical stratification groups allowing to distinguish conditions of absent (FIR 0) from maximal Fetal Inflammatory Response (FIR 3) stratified in function of Maternal Inflammatory Response (MIR) grade. Matrix metallopeptidase-9 (MMP-9) was the top differentially expressed protein. Gene Ontology enrichment analysis of the core proteins showed significant changes in the biological pathways associated to inflammation and regulation of immune and infection response. Data suggest that the conditions determining PTB would be a transversal event, secondary to the maternal inflammatory response causing a breakdown in fetal-maternal tolerance, with fetal inflammation being more severe than maternal one. We also highlight matrix metallopeptidase-9 as a potential predictive biomarker of PTB that can be assayed in the maternal serum, for future investigation.
Cysteine cathepsins are lysosomal enzymes belonging to the papain family. Their expression is misregulated in a wide variety of tumors, and ample data prove their involvement in cancer progression, ...angiogenesis, metastasis, and in the occurrence of drug resistance. However, while their overexpression is usually associated with highly aggressive tumor phenotypes, their mechanistic role in cancer progression is still to be determined to develop new therapeutic strategies. In this review, we highlight the literature related to the role of the cysteine cathepsins in cancer biology, with particular emphasis on their input into tumor biology.
Albumin nanovectors represent one of the most promising carriers recently generated because of the cost-effectiveness of their fabrication, biocompatibility, safety, and versatility in delivering ...hydrophilic and hydrophobic therapeutics and diagnostic agents. In this review, we describe and discuss the recent advances in how this technology has been harnessed for drug delivery in cancer, evaluating the commonly used synthesis protocols and considering the key factors that determine the biological transport and the effectiveness of such technology. With this in mind, we highlight how clinical and experimental albumin-based delivery nanoplatforms may be designed for tackling tumor progression or improving the currently established diagnostic procedures.
Oral administration is an appealing route of delivering cancer treatments. However, the gastrointestinal tract is characterized by specific and efficient physical, chemical, and biological barriers ...that decrease the bioavailability of medications, including chemotherapeutics. In recent decades, the fields of material science and nanomedicine have generated several delivery platforms with high potential for overcoming multiple barriers associated to oral administration. This review describes the properties of several nanodelivery systems that improve the bioavailability of orally administered therapeutics, highlighting their advantages and disadvantages in generating successful anticancer oral nanomedicines.
COVID-19 patients typically present with lower airway disease, although involvement of other organ systems is usually the rule. Hematological manifestations such as thrombocytopenia and reduced ...lymphocyte and eosinophil numbers are highly prevalent in COVID-19 and have prognostic significance. Few data, however, are available about the prevalence and significance of anemia in COVID-19. In an observational study, we investigated the prevalence, pathogenesis and clinical significance of anemia among 206 patients with COVID-19 at the time of their hospitalization in an Internal Medicine unit. The prevalence of anemia was 61% in COVID-19, compared with 45% in a control group of 71 patients with clinical and laboratory findings suggestive of COVID-19, but nasopharyngeal swab tests negative for SARS-CoV-2 RNA (
p
= 0.022). Mortality was higher in SARS-CoV-2 positive patients. In COVID-19, females had lower hemoglobin concentration than males and a higher prevalence of moderate/severe anemia (25% versus 13%,
p
= 0.032). In most cases, anemia was mild and due to inflammation, sometimes associated with iron and/or vitamin deficiencies. Determinants of hemoglobin concentration included: erythrocyte sedimentation rate, serum cholinesterase, ferritin and protein concentrations and number of chronic diseases affecting each patient. Hemoglobin concentration was not related to overall survival that was, on the contrary, influenced by red blood cell distribution width, age, lactate dehydrogenase and the ratio of arterial partial oxygen pressure to inspired oxygen fraction. In conclusion, our results highlight anemia as a common manifestation in COVID-19. Although anemia does not directly influence mortality, it usually affects elderly, frail patients and can negatively influence their quality of life.
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