Two-in-one nanoparticle platform induces a strong therapeutic effect of targeted therapies in P-selectin-expressing cancers.

Combined therapies in cancer treatment aim to enhance antitumor activity. However, delivering multiple small molecules imposes challenges, as different drugs have distinct pharmacokinetic profiles and tumor penetration abilities, affecting their therapeutic efficacy. To circumvent this, poly(lactic-co-glycolic acid) (PLGA)-polyethylene glycol (PEG)-based nanoparticles were developed as a platform for the codelivery of synergistic drug ratios, improving therapeutic efficacy by increasing the percentage of injected dose reaching the tumor.

Concanavalin a Grafted Nanoemulsions for Nasal Delivery: Preliminary Studies with Fluorescently Labelled Formulations.

Nasal delivery is a non-invasive strategy for effective drug delivery. Nevertheless, in order to promote drug uptake by the nasal mucosa, it is fundamental to increase its residence time in the administration site. To this aim, nano-sized drug delivery systems are widely exploited.

Potent antitumor activity of anti-HER2 antibody-topoisomerase I inhibitor conjugate based on self-immolative dendritic dimeric-linker.

Antibody-drug conjugates (ADCs) are a rapidly expanding class of anticancer therapeutics, with 14 ADCs already approved worldwide. We developed unique linker technologies for the bioconjugation of drug molecules with controlled-release applications. We synthesized cathepsin-cleavable ADCs using a dimeric prodrug system based on a self-immolative dendritic scaffold, resulting in a high drug-antibody ratio (DAR) with the potential to reach 16 payloads due to its dendritic structure, increased stability in the circulation and efficient release profile of a highly cytotoxic payload at the targeted site.

Use of Poly Lactic-co-glycolic Acid Nano and Micro Particles in the Delivery of Drugs Modulating Different Phases of Inflammation.

Chronic inflammation contributes to the pathogenesis of many diseases, including apparently unrelated conditions such as metabolic disorders, cardiovascular diseases, neurodegenerative diseases, osteoporosis, and tumors, but the use of conventional anti-inflammatory drugs to treat these diseases is generally not very effective given their adverse effects. In addition, some alternative anti-inflammatory medications, such as many natural compounds, have scarce solubility and stability, which are associated with low bioavailability. Therefore, encapsulation within nanoparticles (NPs) may represent an effective strategy to enhance the pharmacological properties of these bioactive molecules, and poly lactic-co-glycolic acid (PLGA) NPs have been widely used because of their high biocompatibility and biodegradability and possibility to finely tune erosion time, hydrophilic/hydrophobic nature, and mechanical properties by acting on the polymer's composition and preparation technique.

Current Status and Trends in Nucleic Acids for Cancer Therapy: A Focus on Polysaccharide-Based Nanomedicines.

The efficacious delivery of therapeutic nucleic acids to cancer still remains an open issue. Through the years, several strategies are developed for the encapsulation of genetic molecules exploiting different materials, such as viral vectors, lipid nanoparticles (LNPs), and polymeric nanoparticles (NPs). Indeed, the rapid approval by regulatory authorities and the wide use of LNPs complexing the mRNA coding for the spark protein for COVID-19 vaccination paved the way for the initiation of several clinical trials exploiting lipid nanoparticles for cancer therapy.

MCP-1/CCR2 axis inhibition sensitizes the brain microenvironment against melanoma brain metastasis progression.

Development of resistance to chemo- and immunotherapies often occurs following treatment of melanoma brain metastasis (MBM). The brain microenvironment (BME), particularly astrocytes, cooperate toward MBM progression by upregulating secreted factors, among which we found that monocyte chemoattractant protein-1 (MCP-1) and its receptors, CCR2 and CCR4, were overexpressed in MBM compared with primary lesions. Among other sources of MCP-1 in the brain, we show that melanoma cells altered astrocyte secretome and evoked MCP-1 expression and secretion, which in turn induced CCR2 expression in melanoma cells, enhancing in vitro tumorigenic properties, such as proliferation, migration, and invasion of melanoma cells.

Exploring chitosan-shelled nanobubbles to improve HER2 + immunotherapy via dendritic cell targeting.

Immunotherapy is a valuable approach to cancer treatment as it is able to activate the immune system. However, the curative methods currently in clinical practice, including immune checkpoint inhibitors, present some limitations. Dendritic cell vaccination has been investigated as an immunotherapeutic strategy, and nanotechnology-based delivery systems have emerged as powerful tools for improving immunotherapy and vaccine development.

Lipid-Coated Nanocrystals as a Tool for Improving the Antioxidant Activity of Resveratrol.

-resveratrol, a polyphenolic phytoalexin found in various plant sources, has been the focus of increasing attention in recent years because of its role in the prevention of many human diseases, and particularly because of its antioxidant properties. However, the in vivo effect of -resveratrol after oral administration is negligible when compared to its efficacy in vitro, due to its low bioavailability. Moreover, it presents stability issues as it is an extremely photosensitive compound when exposed to light.

Nanotechnology Addressing Cutaneous Melanoma: The Italian Landscape.

Cutaneous melanoma is one of the most aggressive solid tumors, with a low survival for the metastatic stage. Currently, clinical melanoma treatments include surgery, chemotherapy, targeted therapy, immunotherapy and radiotherapy. Of note, innovative therapeutic regimens concern the administration of multitarget drugs in tandem, in order to improve therapeutic efficacy.

Meet me halfway: Are in vitro 3D cancer models on the way to replace in vivo models for nanomedicine development?

The complexity and diversity of the biochemical processes that occur during tumorigenesis and metastasis are frequently over-simplified in the traditional in vitro cell cultures. Two-dimensional cultures limit researchers' experimental observations and frequently give rise to misleading and contradictory results. Therefore, in order to overcome the limitations of in vitro studies and bridge the translational gap to in vivo applications, 3D models of cancer were developed in the last decades.

Nanosponges as protein delivery systems: Insulin, a case study.

Cyclodextrin-based nanosponges have been found to bepromising drug delivery systems. This paper investigates an application that still needs to be studied in depth, that is, the oral delivery of peptides and proteins, choosing insulin as a case study. The nanospongewas synthesized by crosslinkingβ-cyclodextrins withpyromellitic dianhydride, adopting a top-down approach for its subsequent formulation.

Rational Design of Polyglutamic Acid Delivering an Optimized Combination of Drugs Targeting Mutated BRAF and MEK in Melanoma.

Targeted therapies against cancer can relieve symptoms and induce remission, however, they often present limited duration of disease control, cause side effects and often induce acquired resistance. Therefore, there is a great motivation to develop a unique delivery system, targeted to the tumor, in which we can combine several active entities, increase the therapeutic index by reducing systemic exposure, and enhance their synergistic activity. To meet these goals, we chose the biocompatible and biodegradable poly(α,L-glutamic acid) (PGA) as a nanocarrier that facilitates extravasation-dependent tumor targeting delivery.

Persistent Chemiluminescent Glow of Phenoxy-dioxetane Luminophore Enables Unique CRET-Based Detection of Proteases.

Chemiluminescence is being considered an effective imaging modality as it offers low background and high sensitivity. Recent discovery by our group has led to development of new phenoxy-dioxetane chemiluminescence luminophores, which are highly bright under physiological conditions. However, the current scope of probes based on these luminophores is limited, as they can only be turned on by phenol protecting group removal.

Inflammatory Activation of Astrocytes Facilitates Melanoma Brain Tropism via the CXCL10-CXCR3 Signaling Axis.

Melanoma is the deadliest skin cancer due to its high rate of metastasis, frequently to the brain. Brain metastases are incurable; therefore, understanding melanoma brain metastasis is of great clinical importance. We used a mouse model of spontaneous melanoma brain metastasis to study the interactions of melanomas with the brain microenvironment.

Oligo-guanidyl targeted bioconjugates forming rod shaped polyplexes as a new nanoplatform for oligonucleotide delivery.

Novel bioconjugates (Agm-M-PEG-FA) for active oligonucleotide (ON) delivery have been developed by conjugating a cationic oligo-guanidyl star-like shaped "head" (Agm-M) to a polymeric "tail" (PEG) terminating with folic acid (FA) as targeting agent or methoxy group (Agm-M-PEG-FA and Agm-M-PEG-OCH, respectively). Gel electrophoresis showed that the bioconjugates completely associated with ONs at 3 nitrogen/phosphate (N/P) ratio. Studies performed with folate receptor (FR)-overexpressing HeLa cells, showed that optimal cell up-take was obtained with the 75:25 w/w Agm-M-PEG-OCH:Agm-M-PEG-FA mixture.

Nanotechnology is an important strategy for combinational innovative chemo-immunotherapies against colorectal cancer.

Colorectal cancer (CRC) is among the five most commonly diagnosed cancers worldwide, constituting 6% of all cancers and the third leading cause of cancer death. CRC is the third and second most frequent cancer in men and women worldwide, accounting for 14% and 13% of all cancer incidence rates, respectively. CRC incidence is decreasing in older populations, but it has been significantly rising worldwide in adolescents and adults younger than 50 years old.

Light emission enhancement by supramolecular complexation of chemiluminescence probes designed for bioimaging.

Chemiluminescence offers advantages over fluorescence for bioimaging, since an external light source is unnecessary with chemiluminescent agents. This report demonstrates the first encapsulation of chemiluminescence phenoxy-adamantyl-1,2-dioxetane probes with trimethyl β-cyclodextrin. Clear proof for the formation of a 1 : 1 host-guest complex between the adamantyl-1,2-dioxetane probe and trimethyl β-cyclodextrin was provided by mass spectroscopy and NMR experiments.

Molecular Weight-Dependent Activity of Aminated Poly(α)glutamates as siRNA Nanocarriers.

RNA interference (RNAi) can contribute immensely to the area of personalized medicine by its ability to target any gene of interest. Nevertheless, its clinical use is limited by lack of efficient delivery systems. Polymer therapeutics can address many of the challenges encountered by the systemic delivery of RNAi, but suffer from inherent drawbacks such as polydispersity and batch to batch heterogeneity.

Novel Oligo-Guanidyl-PEG Carrier Forming Rod-Shaped Polyplexes.

A novel unconventional supramolecular oligo-cationic structure (Agm-M-PEG-OCH) has been synthesized to yield high efficiency therapeutic oligonucleotide (ON) delivery. Agm-M-PEG-OCH was obtained by a multistep protocol that included the conjugation of agmatine (Agm) moieties to maltotriose (M), which was further derivatized with one poly(ethylene glycol) (PEG) chain. Gel electrophoresis analysis showed that the 19 base pairs dsDNA model ON completely associates with Agm-M-PEG-OCH at 3 N/P molar ratio, which is in agreement with the in silico molecular predictions.

Image-guided surgery using near-infrared Turn-ON fluorescent nanoprobes for precise detection of tumor margins.

Complete tumor removal during surgery has a great impact on patient survival. To that end, the surgeon should detect the tumor, remove it and validate that there are no residual cancer cells left behind. Residual cells at the incision margin of the tissue removed during surgery are associated with tumor recurrence and poor prognosis for the patient.

Structure-Function Analysis of Immune Checkpoint Receptors to Guide Emerging Anticancer Immunotherapy.

The modulation of immune checkpoint receptors has been one of the most successful, exciting, and explored approaches for cancer immunotherapy. Currently, several immune checkpoint modulators, mainly monoclonal antibodies, are showing remarkable results. However, the failure to show a response in most patients and the induction of severe immune-related adverse effects are the major drawbacks.

Direct Real-Time Monitoring of Prodrug Activation by Chemiluminescence.

The majority of theranostic prodrugs reported so far relay information through a fluorogenic response generated upon release of the active chemotherapeutic agent. A chemiluminescence detection mode offers significant advantages over fluorescence, mainly due to the superior signal-to-noise ratio of chemiluminescence. Here we report the design and synthesis of the first theranostic prodrug monitored by a chemiluminescence diagnostic mode.

Amphiphilic poly(α)glutamate polymeric micelles for systemic administration of siRNA to tumors.

RNAi therapeutics carried a great promise to the area of personalized medicine: the ability to target "undruggable" oncogenic pathways. Nevertheless, their efficient tumor targeting via systemic administration had not been resolved yet. Amphiphilic alkylated poly(α)glutamate amine (APA) can serve as a cationic carrier to the negatively-charged oligonucleotides.