Advanced Nanosystems for Clinical Translation

Abstract

This special issue is dedicated, but not limited to, the “1st International Northern-Southern Europe Workshop in Nanomedicine” held in the city of Chieti (Abruzzi, Italy) between January 15–17, 2020, before the COVID-19 pandemic lockdown. The workshop aimed to bring together a vast number of experts with extensive experience in the field of nanomedicine from the northern and southern parts of Europe, but also worldwide to discuss and network on how to foster basic science in translational and personalized nanomedicine for drug delivery applications, including anti-cancer research, regenerative medicine, cardiovascular diseases, polymer and supramolecular chemistry towards reliable pre-clinical and clinical assessment. The final goal of the workshop was to highlight the impact of nanomedicine in pharmaceutical companies and how to create bridges and connections between companies, academia, young and senior scientists. Nanomedicine is the medical application of nanotechnology in different fields of bio- and nano-technology, as well as drug delivery and involves areas related to applications, toxicity and environmental impact of nanoscale materials.[1, 2] Nanomaterials have sizes and structure similar to that of bio- and macro-molecules and their functionalization provides specific properties for tailoring precision medicine and application for many diseases, thus providing different therapeutic options for patients.[3] In particular, nanomedicine integrates different research areas, such as biology, physics, chemistry, materials sciences, nanotechnology and drug delivery in order to develop clinical tools and devices for advanced therapies to patients.[4, 5] In this scenario, nanosystems, having different compositions, combined with nanomaterial properties may foster the translation of basic science in personalized nanomedicines for anti-cancer research, regenerative medicine, cardiovascular diseases, polymer and supramolecular chemistry towards a reliable pre-clinical and clinical assessment.[6-9] Although transparency and reproducibility in nanomedicines is still under discussion,[10] there has been an extensive increase in the benefits of nanomedicine available to patients.[11] This special issue on “Advanced Nanosystems for Clinical Translation” addresses a cutting-edge and multidisciplinary field and emphasises the clinical translation of recently developed advanced nanosystems for a range of readers working both in the academic and industry worlds. Researchers, clinical doctors, related scientific and technical specialists working in chemistry, biomedical sciences, materials science, biology and medicine provide suitable scientific contribution in these fields. There is no doubt that nanomedicine is a cross-, multi-, inter- and trans-disciplinary field of research and the examples below, demonstrate exactly how nanoparticles and nanomedicines are revolutionizing and reshaping the pharmaceutical and biomedical fields. This special issue collects 19 amazing contributions, including eight review papers, nine full papers and two progress reports, which broadly cover the various important topics within the field of nanomedicine. Worldwide contributions are part of this special issue and address the impact of nanosystems in basic science, translational and personalized medicine for the treatment of various diseases. In the field of ultrathin fibers, Prof. Cui and co-workers. from Shanghai Jiao Tong University School of Medicine (article number 2000096) provided a novel analysis of the diverse roles of electrospun nanofibrous scaffolds and summarized recent advances in exploiting their binary attributes for applications in biomedicine. The authors firstly introduced the development of techniques for electrospinning, specifically the engineering of electrospun nanofibers, and then discussed the scaffold applications for cell migration, adhesion, proliferation, and accelerating regeneration in cardiac, nerve, skeletal muscle, bone tissue, and wound healing, as well as the scaffold inhibitory properties in cancer treatments, antibacterial applications, anti-adhesion, anti-scarring, and inhibition of thrombus formation. In the field of brain drug delivery, Prof. Merkel and co-workers from Ludwig-Maximilians-University of Munich (article number 2000092) discussed the impact and properties of apolipoprotein E (ApoE)-functionalized polymeric nanoparticles (NPs) for the transport of drugs, such as dalargin, loperamide, doxorubicin, and nerve growth factor across the brain-blood-barrier (BBB) via low density lipoprotein receptor. The authors also described the direct and indirect coating processes of Apo-E to NPs, their impact in transcytosis mediated transport across the BBB and in vivo models simulating the central nervous system-relevant diseases, such as Alzheimer's or Parkinson's diseases and cerebral cancer. In the field of anticancer therapy, Prof. Teesalu and co-workers from University of Tartu (article number 2000097) discussed the synthesis of silver nanoparticles (AgNP) coated with monomethyl auristatin E (MMAE), a lysosomal protease cathepsin B sensitive linker, and functionalized with a prototypic CendR peptide (RPARPAR), that targets neuropilin-1 (NRP-1), for the treatment of pancreatic and melanoma cells. The authors demonstrated, for example, that RPARPAR-MMAE-AgNPs are internalized and induced apoptotic cell death in NRP-1-positive PPC-1 prostate cancer cells, while sparing NRP-1-negative M21 melanoma cells. In the same field, Prof. Cameron and co-workers from University of Nottingham (article number 2000103) investigated the synthesis of amphiphilic block co-polymers composed of doxorubicin-loaded poly(ethylene glycol)-copoly(lactide)-copoly(2-((tert-butoxycarbonyl)amino)-3-propyl carbonate) and studied its anticancer property in 2D cell models and in 3D spheroids of triple negative breast cancer cells, as well as in an aggressive orthotopic triple negative breast cancer mouse model. In another study, Prof. Kostarelos and co-workers from University of Manchester (article number 2000109) investigated the interaction of graphene oxide (GO) sheets with in vitro (three-dimensional spheroids) and in vivo (orthotopic xenograft) models of glioblastoma (GB). In vitro experiments with spheroids, showed that GO flakes are passively translocated into the spheroids with little internalization in tumor cells, and did not cause cytotoxicity and only induced small changes in gene and protein expression. In vivo, the intracranially administered GO also showed extensive distribution throughout the tumor mass and had no impact on tumor growth and progression for the duration of the study. Furthermore, Prof. Fresta and co-workers from University of Catanzaro “Magna Graecia” (article number 2000121) studied the anticancer effect of multidrug liposomes in breast cancer cells. The co-delivery of anticancer drugs (gemcitabine hydrochloride and paclitaxel) increased the anticancer effect of both drugs in vitro, inhibiting the tumor growth in an in vivo model of metastatic murine breast cancer and improved the overall survival of murine breast cancer metastatic model. Prof. Satchi-Fainaro and co-workers from Tel Aviv University (article number 2000124) provided an overview of drug delivery and novel therapeutic approaches to target GB. The authors firstly discussed the conventional and gold-standard treatments in GB, including surgical resection followed by chemotherapy and radiotherapy, and then the limitations of conventional treatment to achieve complete resection of the tumor, in the majority of GB patients due to the invasiveness of GB and the limitations of drug penetration across the BBB. The authors also reported a detailed overview of novel nanomedicines that can cross the BBB and specifically target the cancer cells to achieve a targeted treatment of GB. Moreover, Prof. Vicent and co-workers from Centro de Investigación Príncipe Felipe (article number 202000136) provided a detailed revision of literature on the current options for prostate cancer (PCa) treatment. The authors reported discussions in hormonal therapy, chemotherapy, immunotherapy, and radiotherapy, the reformulation of existing therapeutics as nanomedicines, and described the nanomedicine approaches to advanced PCa treatment under evaluation in both preclinical and clinical studies. The opportunity to improve the design of novel therapeutic approaches, the identification of novel functional biomarkers to stratify patients, and finally the guidelines for nanomedicine design were also discussed. In the field of cancer nanomedicine, Prof. Florindo and co-workers from Universidade de Lisboa (article number 2000147) discussed the nanomedicines and their impact in melanoma therapy. The authors addressed the current knowledge on melanoma biology and immunology, focusing on the emerging role of nanotechnology in the development of combinatorial strategies targeting and regulating the function of major players in melanoma progression and immune evasion. The impact of nanotechnology was also approached in cancer immunotherapy and the emergent-targeted nanomedicines for immunotherapy were also discussed for their relevance to melanoma genomics, predictive biomarkers, clinical trial design, and clinical regulation of nanomedicines. Furthermore, Prof. Cabral and co-workers from University of Tokyo (article number 2000159) provided an overview of clinical translation of self-assembled nanomedicines for anti-cancer therapy. In particular, the authors reported the process for designing nanomedicines to have a selective delivery of probes and anticancer agents to tumors, and thus, achieving an improved diagnostic or therapeutic efficacy, as well as relieving potential side effects. They also presented the current status of clinically used self-assembled nanomedicines, reviewing recent advances of nanomedicines in clinical trials, discussing the challenges and future perspectives of nanomedicines in the clinic. Prof. Sosnik and co-workers from Technion-Israel Institute of Technology (article number 2000010) investigated the potential of glycosylation to have an active targeting of nano-drug delivery systems for the treatment of solid tumors in patients overexpressing glucose transporters. Curcumin-loaded targeted micelles in the presence of glucose molecules on the surface of micelles lead to enhanced internalization of micelles inside breast cancer cells and increased the anticancer activity both in vitro and in vivo, in mice bearing 4T1-induced tumors. In the field of gene delivery, Prof. Shen and co-workers (article number 2000099) from Houston Methodist Research Institute provided an overview of mRNA-based therapeutics as platform for treatment of human diseases. Multiple nanotechnology-based delivery platforms for mRNA delivery were discussed, such as polymer-based polyplex, lipid-based lipoplex, and lipid-coated polymer-based lipopolyplex, and their applications in biotechnology, including cell reprogramming and gene editing, as well as the potential clinical translational in protein replacement therapy, infectious disease and anti-cancer therapy. Prof. Mitchell and co-workers from University of Pennsylvania (article number 2000111) discussed the potential use of nucleic acids, such as small interfering RNAs (siRNA) and antisense oligonucleotides, in gastrointestinal (GI) diseases. The authors described the use of lipid nanoparticles (LNPs) as an emerging delivery system that can protect nucleic acids from degradation, mediate their intracellular delivery and deliver intact siRNA and antisense oligonucleotides through the gastrointestinal barrier. Lipid compositions of LNPs enhance the delivery of nanosystems in the GI tract and improve the LNP-b-DNA delivery. Moreover, sequencing results and high-throughput in vivo screening indicated that LNPs accelerate the discovery of LNPs for GI tract nucleic acid delivery upon oral administration. In another work, Prof. Zhang and co-workers from Åbo Akademi University (article number 2000072) described the effective intracellular delivery of CRISPR/Cas9 plasmids for homology-directed repair by functionalization of mesoporous silica nanoparticles (MSNs). Functionalized MSNs, forming complexes with CRISPR/Cas9 plasmids, which can enhance the cellular internalization and endosomal escape, facilitating the nuclear transport of the CRISPR/Cas9 plasmids. CRISPR/Cas9 plasmids-functionalized MSNs were shown to aid the overcoming of physiological barriers, allowing the delivery through the GI tract and regulating the intracellular signaling of CRISPR/Cas9 plasmids. In the field of osteoarthritis, Prof. Duvall and co-workers from Vanderbilt University (article number 2000072) described an overview of the recent advances in clinical translation of intra-articular osteoarthritis (OA) and potential nanosystems that are currently used for its treatment. In particular, the authors reported the recent development of clinically tested therapies for OA, and highlighting the recent nanosystems, such as hydrogels, liposomes, polymeric microparticles and nanoparticles, drug conjugates, and combination systems that are currently in clinical trials and have had a significant impact in nanomedicine. In the topical drug delivery field, Prof. Chiappini and co-workers from King's College London (article number 2000160) provided an overview of nanodelivery systems to overcome physiological barriers and to guarantee the passage through the skin, mucosae, eyes and ears for target diseases and accumulation of drugs in specific tissues. In the field of anti-bacterial drug delivery, Prof. Zhou and co-workers from Zhejiang University (article number 2000107) demonstrated that a hydrogel based on photosynthetic microorganisms can enhance wound healing by production and local delivery of oxygen that is carried out to alleviate acute and chronic tissue hypoxia. The authors demonstrated that chlorophyll was released from spirulina platensis coated with carboxymethyl after being irradiated with a 650-nm laser, generating reactive oxygen species (ROS) and leading to photodynamic destruction of bacteria in the infectious area. In another paper, Prof. de la Fuente and co-workers from Instituto de Nanociencia y Materiales de Aragón (article number 2000113) highlighted the importance and progress of pulmonary administration, via passive and active targeting strategies towards bacteria reservoirs to overcome the challenges in tuberculosis treatment. In the field of anti-inflammatory drug delivery, Prof. Santos and co-workers from University of Helsinki (article number 2000058) described a nanocomposite, polydopamine-based nanoparticle, for anti-inflammatory delivery of budesonide encapsulated in a pH-responsive endosomolytic polymer, in order to prevent ROS production and acting as scavenger for inflammation. The authors demonstrated such nanocomposite led to successfully macrophage phenotype and switch from pro-inflammatory M1 to anti-inflammatory M2 macrophages. Overall, this special issue is expected to provide important background and new knowledge on the latest advances of nanomaterials/nanomedicines and their biomedical applications. The guest editors of this special issue are very grateful to all authors who accepted our invitation and contributed with their amazing works to this exciting issue on advanced nanosystems for clinical translation. This Special Issue is dedicated to the “1st International Northern-Southern Europe Workshop in Nanomedicine” hold in the city of Chieti (Abruzzi, Italy) in January 15–17, 2020, and to all the scientists working in the field of nanomedicine and other related fields. Finally, our special thanks go also to the editors and staff of Advanced Therapeutics for their continuous support for this special issue and for making this possible. Christian Celia is an Associate Professor in Pharmaceutical Technology and Advanced Drug Delivery at the University of Chieti – Pescara “. Christian Celia got his PharmD with residence in Hospital Pharmacy in 2008 at the University of Catanzaro and the PhD in Pharmaceutical Science in 2012 in the same institution. He spent two years as a visiting scholar at Houston Methodist Research Institute, Houston, Texas, USA in the Department of Nanomedicine where he rose to the position of Affiliated Scientist in 2012. In 2012, he joined the Department of Pharmacy at the University of Chieti – Pescara as an Assistant Professor and was promoted to Associate Professor in 2017. The research activity of Prof. Celia is focused on advanced drug delivery for anticancer therapy, cutaneous diseases and regenerative medicine. Donatella Paolino is Full Professor in Pharmaceutical Technology and Advanced Drug Delivery at the University Magna Graecia of Catanzaro. She got her PhD in Technology of bioactive substances in 2004 at the University of Palermo, and PharmD in Hospital Pharmacy at the University of Catania. Her teaching responsibilities are in undergraduate and PhD programs. Her scientific interests are design, preparation, characterization and evaluation, both in vitro and in vivo, of innovative colloidal drug delivery systems for the topical administration, (ophthalmic, dermal, transdermal, mucosal and transmucosal) of drugs. Hélder A. Santos obtained his Doctor of Science in Technology (Chemical Engineering) in 2007 from the Helsinki University of Technology (now Aalto University) in Finland. Currently, he is a Full Professor in Pharmaceutical Nanotechnology at the Faculty of Pharmacy, University of Helsinki, and Head of the Nanomedicines and Biomedical Engineering research group. His scientific expertise lies in the development of nanoparticles/nanomedicines for biomedical applications, particularly porous silicon and polymeric-based nanomaterials, for simultaneous controlled drug delivery, diagnostic, and therapy for cancer, diabetes, and cardiovascular diseases.