Serena Mazzucchelli

• Biology
• RTD-A at University of Milan

Triple-negative breast cancer is an aggressive breast cancer subtype characterized by the absence of human epidermal growth factor receptor 2, estrogen and progesterone receptors, limiting targeted therapy options. Cisplatin, a chemotherapeutic agent, induces DNA damage and exhibits some efficacy against triple-negative breast cancer, but its effec...

Background: Growing evidence shows that the reprogramming of fatty acid (FA) metabolism plays a key role in HER2-positive (HER2 +) breast cancer (BC) aggressiveness, therapy resistance and cancer stemness. In particular, HER2 + BC has been defined as a "lipogenic disease" due to the functional and bi-directional crosstalk occurring between HER2-me...

Background The global demographic shift towards an aging population is generating a rise in neurodegenerative conditions, with Alzheimer’s disease (AD) as the most prominent problem. In this landscape, the use of natural supplements has garnered attention for their potential in dementia prevention. Curcumin (Cur), derived from Curcuma longa, has de...

Colorectal cancer (CRC) remains challenging to diagnose, necessitating the identification of a noninvasive biomarker that can differentiate it from other conditions such as inflammatory bowel diseases (IBD) and diverticular disease (DD). Raman spectroscopy (RS) stands out as a promising technique for monitoring blood biochemical profiles, with the...

Extracellular vesicles (EVs) are a subgroup of the circulating particles, released by cells in both normal and diseased states, carrying active biomolecules. They have gained significant attention as potential cancer biomarkers, particularly in breast cancer (BC). Previous research showed variations in EVs content and quantity between BC patients a...

Background A reliable preclinical model of patient-derived organoids (PDOs) was developed in a case study of a 69-year-old woman diagnosed with breast cancer (BC) to investigate the tumour evolution before and after neoadjuvant chemotherapy and surgery. The results were achieved due to the development of PDOs from tissues collected before (O-PRE) a...

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 efficac...

Despite the advent of numerous targeted therapies in clinical practice, anthracyclines, including doxorubicin (DOX), continue to play a pivotal role in breast cancer (BC) treatment. DOX directly disrupts DNA replication, demonstrating remarkable efficacy against BC cells. However, its non-specificity toward cancer cells leads to significant side ef...

We investigated the relevance of encapsulation in H-ferritin nanocages (HFn) in determining an improved tumor-targeted delivery of indocyanine green (ICG). Since from previous experiments, the administration of HFn loaded with ICG (HFn-ICG) resulted in an increased fluorescence signal of ICG, our aim was to uncover if the nanoformulation could have...

Lipoproteins (LPs) are multimolecular complexes of lipids and proteins responsible for transporting fatty acids, cholesterol, and micronutrients (carotenoids) through the body. The quantification of triglycerides and cholesterol carried by lipoproteins is a leading clinical parameter to assess the increased risk of cardiovascular events. However, i...

Background Chemotherapy with anthracyclines, such as doxorubicin (DOX), still remains a mainstay in cancer treatment. DOX kills tumor cells by direct interference with DNA replication, thus it is very effective against highly proliferating cells. Since DOX is not cell-specific drug, it displays severe side effects that limit its clinical use. Besid...

Biological nanoparticles, such as proteins and extracellular vesicles, are rapidly growing as nanobased drug-delivery agents due to their biocompatibility, high loading efficiency, and bioavailability. However, most of the candidates emerging preclinically hardly confirm their potential when entering clinical trials. Among other reasons, this is du...

Due to its unique architecture and innate capability to specifically target cancer cells, ferritin has emerged as an attractive class of biomaterials for drug delivery. In many studies, various chemotherapeutics have been loaded into ferritin nanocages constituted by H-chains of ferritin (HFn), and their related anti-tumor efficacy has been explore...

Background: Bisdemethoxycurcumin (BDC) might be an inflammation inhibitor in Alzheimer’s Disease (AD). However, BDC is almost insoluble in water, poorly absorbed by the organism, and degrades rapidly. We thus developed a new nanoformulation of BDC based on H-Ferritin nanocages (BDC-HFn). Methods: We tested the BDC-HFn solubility, stability, and abi...

In the last couple of decades, nanoparticles have been extensively studied as carriers for cancer imaging agents and as drug delivery platforms, due to their ability to positively affect the distribution and tumor-targeting properties of delivered compounds [...]

Human epidermal growth factor receptor-2 (HER-2) overexpressing breast cancer is a breast cancer subtype characterized by high aggressiveness, high frequency of brain metastases and poor prognosis. HER-2, a glycoprotein belonging to the ErbB receptor family, is overexpressed on the outer membrane of cancer cells and has been an important therapeuti...

Loss of pancreatic beta cells is a central feature of type 1 (T1D) and type 2 (T2D) diabetes, but a therapeutic strategy to preserve beta cell mass remains to be established. Here we show that the death receptor TMEM219 is expressed on pancreatic beta cells and that signaling through its ligand insulin-like growth factor binding protein 3 (IGFBP3)...

Indocyanine green (ICG) is one of the most commonly used fluorophores in near-infrared fluorescence-guided techniques. However, the molecule is prone to form aggregates in saline solution with a limited photostability and a moderate fluorescence yield. ICG was thus formulated using protein-based nanoparticles of H-ferritin (HFn) in order to generat...

Protein nanocages have been studied extensively, due to their unique architecture, exceptional biocompatibility and highly customization capabilities. In particular, ferritin nanocages (FNs) have been employed for the delivery of a vast array of molecules, ranging from chemotherapeutics to imaging agents, among others. One of the main favorable cha...

Background: Bariatric surgery (BS) is an important procedure used for the treatment of morbid obesity and has been proven to improve, or even cure, type 2 diabetes mellitus (T2DM). However, of the patients with T2DM who initially go into remission, a proportion experience a relapse during the follow-up. In this context, Raman spectroscopy (RS) coul...

A major concern in the management of Inflammatory Bowel Disease (IBD) is the absence of accurate and specific biomarkers to drive diagnosis and monitor disease status timely and non-invasively. Fibroblast activation protein (FAP) represents a hallmark of IBD bowel strictures, being overexpressed in stenotic intestinal myofibroblasts. The present st...

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 personaliz...

High-density lipoproteins (HDLs) represent a class of lipoproteins very heterogeneous in structure, composition, and biological functions, which carry out reverse cholesterol transport, antioxidant, anti-inflammatory, antithrombotic, and vasodilator actions. Despite the evidence suggesting a clear inverse relationship between HDL cholesterol (HDL-c...

Background Currently, a major point of concern in the management of Inflammatory Bowel Diseases (IBD) is the absence of accurate and specific circulating biomarkers able to drive diagnosis in a timely and noninvasive manner. Aim of the present study was to explore blood biomarkers of IBD by coupling the targeted detection of circulating fibroblast...

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...

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...

Indocyanine green (ICG) is a near infrared fluorescent tracer used in image-guided surgery to assist surgeons during resection. Despite appearing as a very promising tool for surgical oncology, its employment in this area is limited to lymph node mapping or to laparoscopic surgery, as it lacks tumor targeting specificity. Recently, a nanoformulatio...

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. Here, with the aim of developing CAF-targeted drug delivery agents, we functionalized H-ferritin (HFn) nanocages wit...

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 p...

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 i...

Everolimus (Eve) is an immunosuppressive macrolide that is being analyzed in various biological matrices and fluids. Its antitumor activity makes this drug suitable not only for organ transplantation but also for breast cancer treatments. In the attempt to reduce the incidence and severity of its side effects, Eve was loaded in H-ferritin (HFn), a...

Indocyanine green (ICG) is a Food and Drug Administration–approved near-infrared fluorescent dye, employed as an imaging agent for different clinical applications due to its attractive physicochemical properties, high sensitivity, and safety. However, free ICG suffers from some drawbacks, such as relatively short circulation half-life, concentratio...

Neoadjuvant chemotherapy has been established as the standard of care for HER2-positive breast cancer since it allows cancer down-staging, up to pathological complete response. The standard of care in the neoadjuvant setting for HER2-positive breast cancer is a combination of highly cytotoxic drugs such as anthracyclines and the anti-HER2 monoclona...

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. Th...

Systemic chemotherapy has not significantly reduced clinical demand for triple negative breast cancer (TNBC) treatments. To address the need for more effective therapy, the use of nonviral nanoparticles is explored to deliver suicide gene therapy as valuable alternative to protect nucleic acids in the bloodstream and improve their tumor uptake. Bio...

Backgrounds & aims: There is no accurate and reliable circulating biomarker to diagnose Crohn's disease (CD). Raman spectroscopy is a relatively new approach that provides information on the biochemical composition of samples in minutes and virtually without any sample preparation. We aimed to test the use of Raman spectroscopy analysis of plasma...

Raman spectroscopy has been vastly employed for the characterization of different bio-molecular species spanning from single protein to the in-vivo analysis of tissues. However, despite the huge work done, a detailed description of the Raman spectra acquired from the main classes of plasma lipoproteins is still missing. In this work, we extracted,...

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. We...

Background: The oncologic benefit of upfront re-excision of involved margins after breast-conserving surgery in the context of current multimodal clinical management of breast cancer is unclear. The aim of the present study was to assess the 5-years locoregional recurrence (LRR)-free and distant metastases (DM)-free survival probabilities in patie...

LncRNAs play crucial roles in cellular processes and their regulatory effects in the adult brain and neural stem cells (NSCs) remain to be entirely characterized. We report that 10 lncRNAs (LincENC1, FABL, lincp21, HAUNT, PERIL, lincBRN1a, lincBRN1b, HOTTIP, TUG1 and FENDRR) are expressed during murine NSCs differentiation and interact with the RNA...

Background: Patient-derived organoids (PDO) technology represents an emerging tool for the study of tumor biology and drug responsiveness, thus being useful to design personalized medicine approaches. Despite several studies and clinical trials are ongoing using PDO from colorectal and pancreatic cancer, only few research papers have been publishe...

Introduction: Autologous fat transfer (AFT) is widely adopted for breast reconstruction, but its long-term oncologic safety is still not clearly established. The aim of the present study was to compare the 10-year loco-regional recurrence (LRR)-free and distant metastases (DM)-free survival probabilities in AFT vs. control patients, also evaluatin...

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 a...

This abstract was withdrawn by the authors. Citation Format: Corsi F, Andreata F, Truffi M, Sorrentino L, D'Addio F, Monieri M, Gambaro A, Bellini M, Prosperi D, Mazzucchelli S. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):A...

Background: HER2⁺ breast cancer (BC) accounts for 20-25 % of BCs and it is characterized by high aggressiveness.¹ Despite the anti-HER2 monoclonal antibody Trastuzumab (TZ) has improved BC clinical outcome, it could induce severe cardiac reversible dysfunction:² HER2 signaling is also essential for growth and survival of myocardiocytes.³ Therefore,...

Background and Objectives An accurate localization is mandatory to tailor breast lumpectomy in nonpalpable cancers. The aim of this study was to compare radio‐guided localization (ROLL) vs ultrasound localization of a titanium clip with collagen (TCC) in nonpalpable mass‐like breast cancers. Methods Two hundred seventy‐three consecutive patients w...

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 imp...

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...

Background: Intraoperative radiotherapy (IORT) could be not-inferior to external beam radiotherapy (EBRT) in selected patients, but toxicities, self-perception of body image, quality of life, and resumption of work or daily activities have been poorly explored. The aim of the present study was to compare these outcomes between EBRT, IORT full-dose...

Successful application of nanoconjugates either in vitro or in vivo does depend on the design strategy used for their development. In this chapter, we focus on the most important factors that need to be taken into account to optimize nanoparticle biofunctionalization and provide an overview of recent approaches yielding the efficient and orientatio...

Background: The identification of new strategies aimed to optimize the treatment of breast cancer and its metastases represents a great technical and medical challenge. Target-specific therapies, such as Trastuzumab (TZ), have revolutionized the clinical scenario in certain subsets of cancer. However, the huge variability in response to therapy and...

Background: Currently the standard techniques for sentinel node (SLN) detection in breast cancer are radioisotope (RI) and blue dye, but both methods present some drawbacks. Indocyanine green (ICG) fluorescence has been recently proposed as an alternative technique. However, the equipment to detect ICG fluorescence is not widely accessible, limitin...

Background: PolyADP-ribose polymerase (PARP) inhibitors are a novel promising strategy toward triple-negative breast cancer (TNBC), which often shows genomic instability or BRCA mutations. However, clinical results are controversial, and no benefits were demonstrated in case of wild type BRCA, possibly due to poor bioavailability, and inadequate nu...

Background: The equipment to detect indocyanine green (ICG) fluorescence for sentinel lymph node (SLN) biopsy in breast cancer is not widely accessible nor optimal. The fluorescence appears as a poorly defined white shine on a black background, and dimmed lighting is required. The aim of this study was to assess the feasibility, accuracy and healt...

Background Crohn’s disease (CD) is a chronic bowel inflammation that ultimately leads to fibrosis, for which medical therapy is currently unavailable. Fibrotic strictures in CD are characterized by excessive extracellular matrix (ECM) deposition, altered balance between matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), and overe...

Background Bowel fibrosis is a chronic and progressive process characterised by excessive deposition of extracellular matrix (ECM) and imbalance between matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). This phenomenon represents a severe end-stage of some chronic inflammatory disorders such as Crohn’s disease (CD), for which ef...

Poly(ADP-ribose) polymerase (PARP) inhibitors represent a promising strategy toward the treatment of triple-negative breast cancer (TNBC), which is often associated to genomic instability and/or BRCA mutations. However, clinical outcome is controversial and no benefits have been demonstrated in wild type BRCA cancers, possibly due to poor drug bioa...

Chemotherapeutic treatment of breast cancer is based on maximum tolerated dose (MTD) approach.1 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 administrationsat lower doses,...

Background Currently, reinterventions for involved margins after breast-conserving surgery remain common. The aim of this study was to assess the capability of the cavity shave margins (CSM) technique to reduce positive margin rates and reoperations compared with simple lumpectomy (SL). The impact of CSM on the various biological portraits of breas...

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,...

Supplementary Figures, Supplementary Tables.

Active targeting of nanoparticles to tumours can be achieved by conjugation with specific antibodies. Specific active targeting of the HER2 receptor is demonstrated in vitro and in vivo with a subcutaneous MCF-7 breast cancer mouse model with trastuzumab-functionalized gold nanoparticles. The number of attached antibodies per nanoparticle was preci...

This study describes the development of simple, rapid and sensitive liquid chromatography tandem mass spectrometry method for the simultaneous analysis of doxorubicin and its major metabolite, doxorubicinol, in mouse plasma, urine and tissues. The calibration curves were linear over the range 5-250 ng/ml for doxorubicin and 1.25-25 ng/ml for doxoru...

logo Search In Vitro Permeation of FITC-loaded Ferritins Across a Rat Blood-brain Barrier: a Model to Study the Delivery of Nanoformulated Molecules SUMMARY ABSTRACT Brain microvascular endothelial cells, supported by pericytes and astrocytes endfeet, are responsible for the low permeation of large hydrosoluble drugs through the blood-brain ba...

In HIV-1 management, eradication of the virus from sanctuaries represents a major and challenging goal. The genital tract, gut associated lymphoid tissue, lymph nodes, central nervous system, macrophages and latently infected CD4+ T lymphocytes are typical sites where HIV-1 compartmentalizes. To circumvent this problem, a consistent number of studi...

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 gastroresista...

Metastatic breast cancer represents a diagnostic and therapeutic challenge due to tumor heterogeneity and to various physiological barriers that hinder drug delivery to the metastatic sites. To overcome these limitations, nanoformulated drugs have been developed and tested in preclinical studies, and few of them have been successfully translated in...