Conjugation of gold nanoparticles with multidentate surfactants for enhanced stability and biological properties.

This work originated from the need to functionalize surfactant-coated inorganic nanoparticles for biomedical applications, a process that is limited by excess unbound surfactant. These limitations are connected to the bioconjugation of targeting molecules that are often in equilibrium between the free aliquot in solution and that which binds the surface of the nanoparticles. The excess in solution can play a role in the biocompatability and of the final nanoparticles stock.

Specific immunosuppressive role of nanodrugs targeting calcineurin in innate myeloid cells.

Calcineurin (CN) inhibitors currently used to avoid transplant rejection block the activation of adaptive immune responses but also prevent the development of tolerance toward the graft, by directly inhibiting T cells. CN, through the transcription factors of the NFAT family, plays an important role also in the differentiation dendritic cells (DCs), the main cells responsible for the activation of T lymphocytes. Therefore, we hypothesized that the inhibition of CN only in DCs and not in T cells could be sufficient to prevent T cell responses, while allowing for the development of tolerance.

Isolation of Primary Cancer-Associated Fibroblasts from a Syngeneic Murine Model of Breast Cancer for the Study of Targeted Nanoparticles.

Cancer-associated fibroblasts (CAFs) are key actors in the context of the tumor microenvironment. Despite being reduced in number as compared to tumor cells, CAFs regulate tumor progression and provide protection from antitumor immunity. Emerging anticancer strategies aim to remodel the tumor microenvironment through the ablation of pro-tumorigenic CAFs or reprogramming of CAFs functions and their activation status.

Evaluation of TFR-1 Expression in Feline Mammary Cancer and In Vitro Antitumor Efficacy Study of Doxorubicin-Loaded H-Ferritin Nanocages.

The transferrin receptor 1 (TFR-1) has been found overexpressed in a broad range of solid tumors in humans and is, therefore, attracting great interest in clinical oncology for innovative targeted therapies, including nanomedicine. TFR-1 is recognized by H-Ferritin (HFn) and has been exploited to allow selective binding and drug internalization, applying an HFn nanocage loaded with doxorubicin (HFn(DOX)). In veterinary medicine, the role of TFR-1 in animal cancers remains poorly explored, and no attempts to use TFR-1 as a target for drug delivery have been conducted so far.

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.

H-Ferritin nanoparticle-mediated delivery of antibodies across a BBB in vitro model for treatment of brain malignancies.

Brain cancers are a group of neoplasms that can be either primary, such as glioblastoma multiforme (GBM), or metastatic, such as the HER2+ breast cancer brain metastasis. The brain represents a sanctuary for cancer cells thanks to the presence of the blood brain barrier (BBB) that controls trafficking of molecules, protecting the brain from toxic substances including drugs. Considering that GBM and HER2+ breast cancer brain metastases are characterized by EGFR and HER2 over-expression respectively, CTX- and TZ-based treatment could be effective.

Modeling the interaction of amphiphilic polymer nanoparticles with biomembranes to Guide rational design of drug delivery systems.

Nanoparticle assisted drug delivery to the cytoplasm is limited by sequestration of nanoparticles in endosomes. Endosomal escape through polymer-induced membrane destabilization is one of a few well characterized mechanisms to overcome it. Aiming to utilize this method in vivo, it is necessary to understand how modulating the structural and chemical features of the polymer and the presence of proteins in biological fluids can affect this activity.

Engineered Ferritin Nanoparticles for the Bioluminescence Tracking of Nanodrug Delivery in Cancer.

The identification of a highly sensitive method to check the delivery of administered nanodrugs into the tumor cells is a crucial step of preclinical studies aimed to develop new nanoformulated cures, since it allows the real therapeutic potential of these devices to be forecast. In the present work, the ability of an H-ferritin (HFn) nanocage, already investigated as a powerful tool for cancer therapy thanks to its ability to actively interact with the transferrin receptor 1, to act as an efficient probe for the monitoring of nanodrug delivery to tumors is demonstrated. The final formulation is a bioluminescent nanoparticle, where the luciferin probe is conjugated on nanoparticle surface by means of a disulfide containing linker (Luc-linker@HFn) which is subjected to glutathione-induced cyclization in tumor cell cytoplasm.

Thirty Years of Cancer Nanomedicine: Success, Frustration, and Hope.

Starting with the enhanced permeability and retention (EPR) effect discovery, nanomedicine has gained a crucial role in cancer treatment. The advances in the field have led to the approval of nanodrugs with improved safety profile and still inspire the ongoing investigations. However, several restrictions, such as high manufacturing costs, technical challenges, and effectiveness below expectations, raised skeptical opinions within the scientific community about the clinical relevance of nanomedicine.

Are nanotechnological approaches the future of treating inflammatory diseases?

The current treatments for chronic inflammatory diseases cause severe side effects due to nonspecific drug accumulation. Nanotechnology opens the way to new therapeutic strategies that exploit the ability of immune cells, and especially of phagocytes, to internalize nanoparticles. The cellular uptake of nanoparticles requires specific interactions and is affected by the chemical and physical properties of the carriers.

Half-Chain Cetuximab Nanoconjugates Allow Multitarget Therapy of Triple Negative Breast Cancer.

The use of therapeutic monoclonal antibodies (mAbs) has revolutionized cancer treatment. The conjugation of mAbs to nanoparticles has been broadly exploited to improve the targeting efficiency of drug nanocarriers taking advantage of high binding efficacy and target selectivity of antibodies for specific cell receptors. However, the therapeutic implications of nanoconjugation have been poorly considered.

Impact of the strategy adopted for drug loading in nonporous silica nanoparticles on the drug release and cytotoxic activity.

Nanoparticles are normally classified as "hard", mainly consisting of metal or metal oxide cores, or "soft", including polymer-based, liposomes and biomimetic nanoparticles. Soft nanoparticles have been studied in depth for drug formulation and therapeutic delivery applications, albeit hard nanoparticles may offer easier synthesis, smaller size and more effective tumor penetration. Among them, silica nanoparticles maintain excellent biocompatibility and biodegradability and can be finely adjusted in size and shape, easily produced in a large scale and functionalized or loaded with active molecules.

H-Ferritin Enriches the Curcumin Uptake and Improves the Therapeutic Efficacy in Triple Negative Breast Cancer Cells.

Triple negative breast cancer (TNBC) is a highly aggressive, invasive, and metastatic tumor. Although it is reported to be sensitive to cytotoxic chemotherapeutics, frequent relapse and chemoresistance often result in treatment failure. In this study, we developed a biomimetic nanodrug consisting of a self-assembling variant (HFn) of human apoferritin loaded with curcumin.

Nanometronomic treatment of 4T1 breast cancer with nanocaged doxorubicin prevents drug resistance and circumvents cardiotoxicity.

Chemotherapeutic treatment of breast cancer is based on maximum tolerated dose (MTD) approach. However, advanced stage tumors are not effectively eradicated by MTD owing to suboptimal drug targeting, onset of therapeutic resistance and neoangiogenesis. In contrast, "metronomic" chemotherapy is based on frequent drug administrations at lower doses, resulting in neovascularization inhibition and induction of tumor dormancy.

Protein nanocages for self-triggered nuclear delivery of DNA-targeted chemotherapeutics in Cancer Cells.

A genetically engineered apoferritin variant consisting of 24 heavy-chain subunits (HFn) was produced to achieve a cumulative delivery of an antitumor drug, which exerts its cytotoxic action by targeting the DNA at the nucleus of human cancer cells with subcellular precision. The rationale of our approach is based on exploiting the natural arsenal of defense of cancer cells to stimulate them to recruit large amounts of HFn nanoparticles loaded with doxorubicin inside their nucleus in response to a DNA damage, which leads to a programmed cell death. After demonstrating the selectivity of HFn for representative cancer cells compared to healthy fibroblasts, doxorubicin-loaded HFn was used to treat the cancer cells.