Combined Ferritin Nanocarriers with ICG for Effective Phototherapy Against Breast Cancer.

Introduction: Photodynamic Therapy (PDT) is a promising, minimally invasive treatment for cancer with high immunostimulatory potential, no reported drug resistance, and reduced side effects. Indocyanine Green (ICG) has been used as a photosensitizer (PS) for PDT, although its poor stability and low tumor-target specificity strongly limit its efficacy. To overcome these limitations, ICG can be formulated as a tumor-targeting nanoparticle (NP).

Ferritin nanoconjugates guide trastuzumab brain delivery to promote an antitumor response in murine HER2 + breast cancer brain metastasis.

Brain metastasis (BM) represents a clinical challenge for patients with advanced HER2 + breast cancer (BC). The monoclonal anti-HER2 antibody trastuzumab (TZ) improves survival of BC patients, but it has low central nervous system penetrance, being ineffective in treating BM. Previous studies showed that ferritin nanoparticles (HFn) may cross the blood brain barrier (BBB) through binding to the transferrin receptor 1 (TfR1).

SARS-CoV-2 Immunization Orchestrates the Amplification of IFNγ-Producing T Cell and NK Cell Persistence.

Unlabelled: A successful vaccination would represent the most efficient means to control the pandemic of Coronavirus Disease-19 (COVID-19) that led to millions of deaths worldwide. Novel mRNA-based vaccines confer protective immunity against SARS-CoV-2, but whether immunity is immediately effective and how long it will remain in recipients are uncertain. We sought to assess the effectiveness of a two-dose regimen since the boosts are often delayed concerning the recommended intervals.

Ultrastructural analysis of breast cancer patient-derived organoids.

Background: Breast cancer Patient Derived Organoids (PDO) have been demonstrated to be a reliable model to study cancer that promised to replace and reduce the use of animals in pre-clinical research. They displayed concordance with the tissue of origin, resuming its heterogenicity and representing a good platform to develop approaches of personalized medicines. Although obtain PDOs from mammary tumour, was a very challenging process, several ongoing studies evaluated them as a platform to study efficacy, sensitivity and specificity of new drugs and exploited them in personalized medicine.

Selective Targeting of Cancer-Associated Fibroblasts by Engineered H-Ferritin Nanocages Loaded with Navitoclax.

Cancer-associated fibroblasts (CAFs) are key actors in regulating cancer progression. They promote tumor growth, metastasis formation, and induce drug resistance. For these reasons, they are emerging as potential therapeutic targets.

Combined Method to Remove Endotoxins from Protein Nanocages for Drug Delivery Applications: The Case of Human Ferritin.

Protein nanocages represent an emerging candidate among nanoscaled delivery systems. Indeed, they display unique features that proved to be very interesting from the nanotechnological point of view such as uniform structure, stability in biological fluids, suitability for surface modification to insert targeting moieties and loading with different drugs and dyes. However, one of the main concerns regards the production as recombinant proteins in , which leads to a product with high endotoxin contamination, resulting in nanocage immunogenicity and pyrogenicity.

Mitochondrial Metabolism as Target of the Neuroprotective Role of Erythropoietin in Parkinson's Disease.

Existing therapies for Parkinson's disease (PD) are only symptomatic. As erythropoietin (EPO) is emerging for its benefits in neurodegenerative diseases, here, we test the protective effect driven by EPO in in vitro (SH-SY5Y cells challenged by MPP) and in vivo (C57BL/6J mice administered with MPTP) PD models. EPO restores cell viability in both protective and restorative layouts, enhancing the dopaminergic recovery.

Anti-MAdCAM-1-Conjugated Nanocarriers Delivering Quantum Dots Enable Specific Imaging of Inflammatory Bowel Disease.

Purpose: Assessment of inflammatory bowel disease (IBD) currently relies on aspecific clinical signs of bowel inflammation. Specific imaging of the diseased bowel regions is still lacking. Here, we investigate mucosal addressin cell adhesion molecule 1 (MAdCAM-1) as a reliable and specific endothelial target for engineered nanoparticles delivering imaging agents to obtain an exact mapping of diseased bowel foci.

Development of Tumor-Targeted Indocyanine Green-Loaded Ferritin Nanoparticles for Intraoperative Detection of Cancers.

Indocyanine green (ICG) is a fluorescent dye with a strong emission in the near-infrared spectral range that allows deep signal penetration and minimal interference of tissue autofluorescence. It has been employed in clinics for different applications, among which the more interesting is certainly near-infrared fluorescence image-guided surgery. This technique has found wide application in surgical oncology for lymph node mapping or for laparoscopic surgery.

Everolimus Nanoformulation in Biological Nanoparticles Increases Drug Responsiveness in Resistant and Low-Responsive Breast Cancer Cell Lines.

Everolimus (Eve) is an FDA approved drug that inhibits mammalian target of rapamycin (mTOR). It is employed in breast cancer treatment even if its responsiveness is controversial. In an attempt to increase Eve effectiveness, we have developed a novel Eve nanoformulation exploiting H-ferritin nanocages (HEve) to improve its subcellular delivery.

Nano-Strategies to Target Breast Cancer-Associated Fibroblasts: Rearranging the Tumor Microenvironment to Achieve Antitumor Efficacy.

Cancer-associated fibroblasts (CAF) are the most abundant cells of the tumor stroma and they critically influence cancer growth through control of the surrounding tumor microenvironment (TME). CAF-orchestrated reactive stroma, composed of pro-tumorigenic cytokines and growth factors, matrix components, neovessels, and deregulated immune cells, is associated with poor prognosis in multiple carcinomas, including breast cancer. Therefore, beyond cancer cells killing, researchers are currently focusing on TME as strategy to fight breast cancer.

Multivalent exposure of trastuzumab on iron oxide nanoparticles improves antitumor potential and reduces resistance in HER2-positive breast cancer cells.

Targeted therapies have profoundly changed the clinical prospect in human epidermal growth factor receptor 2 (HER2)-positive breast cancer. In particular, the anti-HER2 monoclonal antibody trastuzumab represents the gold standard for the treatment of HER2+ breast cancer patients. Its contribution in dampening cancer progression is mainly attributed to the antibody-dependent cell-mediated cytotoxicity (ADCC) rather than HER2 blockade.

Human Prostate Tissue-derived Extracellular Matrix as a Model of Prostate Microenvironment.

Background: Clinical experience highlights the wide heterogeneity of primary prostate cancer (PPCa), even when potentially related to the same grade and stage. Currently available prediction tools and biomarkers do not always allow for early recognition of PPCa aggressive phenotype, sometimes making it impossible to distinguish among men harbouring indolent tumours or life-threatening disease.

Objective: To establish a novel ex vivo/in vitro model suitable to estimate the invasive phenotype of PPCa cells (PPCaC).

Nano-targeting of mucosal addressin cell adhesion molecule-1 identifies bowel inflammation foci in murine model.

Aim: We investigate MAdCAM-1 as a reliable target to detect active bowel inflammation for selective noninvasive nanodiagnostics.

Materials & Methods: We coupled anti-MAdCAM-1 antibodies to manganese oxide nanoparticles, and analyzed nanoconjugate biodistribution and safety in murine model of inflammatory bowel disease by imaging and histology.

Results: Nanoparticles were stable and nontoxic.

Bioengineered gold nanoparticles targeted to mesenchymal cells from patients with bronchiolitis obliterans syndrome does not rise the inflammatory response and can be safely inhaled by rodents.

The use of gold nanoparticles (GNPs) as drug delivery system represents a promising issue for diseases without effective pharmacological treatment due to insufficient local drug accumulation and excessive systemic toxicity. Bronchiolitis obliterans syndrome (BOS) represents about 70% of cases of chronic lung allograft dysfunction, the main challenge to long-term lung transplantation. It is believed that due to repeated insults to epithelial bronchiolar cells local inflammatory response creates a milieu that favors epithelial-mesenchymal transition and activation of local mesenchymal cells (MCs) leading to airway fibro-obliteration.

Impact of semi-solid formulations on skin penetration of iron oxide nanoparticles.

Background: This work aimed to provide useful information on the incidence of the choice of formulation in semi-solid preparations of iron-oxide nanoparticles (IONs). The appropriate analytical methods to assess the IONs physical stability and the effect of the semi-solid preparations on IONs human skin penetration were discussed. The physical stability of IONs (D = 31 ± 4 nm; ζ = -65 ± 5 mV) loaded in five semi-solid preparations (0.

Linearized texture of three-dimensional extracellular matrix is mandatory for bladder cancer cell invasion.

In the fields of biomaterials and tissue engineering simulating the native microenvironment is of utmost importance. As a major component of the microenvironment, the extracellular matrix (ECM) contributes to tissue homeostasis, whereas modifications of native features are associated with pathological conditions. Furthermore, three-dimensional (3D) geometry is an important feature of synthetic scaffolds favoring cell stemness, maintenance and differentiation.

"Blind" targeting in action: From phage display to breast cancer cell targeting with peptide-gold nanoconjugates.

Tumor homing peptides (THPs) specific for a representative breast cancer cell line (MCF-7) were carefully selected basing on a phage-displayed peptide library freely available on the web, namely the "TumorHoPe: A Database of Tumor Homing Peptides". The selected THPs were synthesized and evaluated in terms of their affinity toward MCF-7 cells. Out of 5 tested THPs, 3 best-performing peptide sequences and 1 scrambled sequence were separately conjugated to spherical gold nanoparticles yielding stable nanoconjugates.

Oral delivery of insulin via polyethylene imine-based nanoparticles for colonic release allows glycemic control in diabetic rats.

In this study, insulin-containing nanoparticles were loaded into pellet cores and orally administered to diabetic rats. Polyethylene imine-based nanoparticles, either placebo or loaded with insulin, were incorporated by extrusion and spheronization technology into cores that were subsequently coated with three overlapping layers and a gastroresistant film. The starting and coated systems were evaluated in vitro for their physico-technololgical characteristics, as well as disintegration and release performance.

Insight On Colorectal Carcinoma Infiltration by Studying Perilesional Extracellular Matrix.

The extracellular matrix (ECM) from perilesional and colorectal carcinoma (CRC), but not healthy colon, sustains proliferation and invasion of tumor cells. We investigated the biochemical and physical diversity of ECM in pair-wised comparisons of healthy, perilesional and CRC specimens. Progressive linearization and degree of organization of fibrils was observed from healthy to perilesional and CRC ECM, and was associated with a steady increase of stiffness and collagen crosslinking.

Nanoformulation of antiretroviral drugs enhances their penetration across the blood brain barrier in mice.

Unlabelled: Eradication of virus by sanctuary sites is a main goal in HIV management. The central nervous system (CNS) is a classic model of sanctuary where viral replication occurs despite a complete viral suppression in peripheral blood. In recent years, nanotechnologies have provided a great promise in the eradication of HIV from the CNS.

Skin substitutes based on allogenic fibroblasts or keratinocytes for chronic wounds not responding to conventional therapy: a retrospective observational study.

Chronic wounds are an expression of underlying complex pathologies and have a high incidence. Skin substitutes may represent an alternative approach to treat chronic ulcers. The aim of this retrospective observational study was to evaluate the wound reduction using skin substitutes based on allogenic fibroblasts or keratinocytes in 30 patients not responding to conventional therapy.

Cellular localization, invasion, and turnover are differently influenced by healthy and tumor-derived extracellular matrix.

The interplay between tumor cells and the microenvironment has been recognized as one of the hallmarks of cancer biology. To assess the role of extracellular matrix (ECM) in the modulation of tissue homeostasis and tumorigenesis, we developed a protocol for the purification of tissue-derived ECM using mucosae from healthy human colon, perilesional area, and colorectal carcinoma (CRC). Matched specimens were collected from the left colon of patients undergoing CRC resection surgery.

Assessing the in vivo targeting efficiency of multifunctional nanoconstructs bearing antibody-derived ligands.

A great challenge in nanodiagnostics is the identification of new strategies aimed to optimize the detection of primary breast cancer and metastases by the employment of target-specific nanodevices. At present, controversial proof has been provided on the actual importance of surface functionalization of nanoparticles to improve their in vivo localization at the tumor. In the present paper, we have designed and developed a set of multifunctional nanoprobes, modified with three different variants of a model antibody, that is, the humanized monocolonal antibody trastuzumab (TZ), able to selectively target the HER2 receptor in breast cancer cells.

HER2 expression in breast cancer cells is downregulated upon active targeting by antibody-engineered multifunctional nanoparticles in mice.

Subcellular destiny of targeted nanoparticles in cancer cells within living organisms is still an open matter of debate. By in vivo and ex vivo experiments on tumor-bearing mice treated with antibody-engineered magnetofluorescent nanocrystals, in which we combined fluorescence imaging, magnetic relaxation, and trasmission electron microscopy approaches, we provide evidence that nanoparticles are effectively delivered to the tumor by active targeting. These nanocrystals were demonstrated to enable contrast enhancement of the tumor in magnetic resonance imaging.