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Advanced Drug Delivery Reviews (v.64, #13)
Interactions of nanomaterials and biological systems: Implications to personalized nanomedicine
by Xue-Qing Zhang; Xiaoyang Xu; Nicolas Bertrand; Eric Pridgen; Archana Swami; Omid C. Farokhzad (pp. 1363-1384).
The application of nanotechnology to personalized medicine provides an unprecedented opportunity to improve the treatment of many diseases. Nanomaterials offer several advantages as therapeutic and diagnostic tools due to design flexibility, small sizes, large surface-to-volume ratio, and ease of surface modification with multivalent ligands to increase avidity for target molecules. Nanomaterials can be engineered to interact with specific biological components, allowing them to benefit from the insights provided by personalized medicine techniques. To tailor these interactions, a comprehensive knowledge of how nanomaterials interact with biological systems is critical. Herein, we discuss how the interactions of nanomaterials with biological systems can guide their design for diagnostic, imaging and drug delivery purposes. A general overview of nanomaterials under investigation is provided with an emphasis on systems that have reached clinical trials. Finally, considerations for the development of personalized nanomedicines are summarized such as the potential toxicity, scientific and technical challenges in fabricating them, and regulatory and ethical issues raised by the utilization of nanomaterials.Display Omitted
Keywords: Nanomaterials; Nanoparticles; Targeted delivery; Personalized nanomedicine; Nanotechnology; Molecular diagnostic; In vivo; imaging; Protein binding; Receptor-mediated endocytosis
Genomic perspectives in inter-individual adverse responses following nanomedicine administration: The way forward
by S. Moein Moghimi; Peter P. Wibroe; Shen Y. Helvig; Z. Shadi Farhangrazi; A. Christy Hunter (pp. 1385-1393).
The underlying mechanism of intravenous infusion-related adverse reactions inherent to regulatory-approved nanomedicines still remains elusive. There are substantial inter-individual differences in observed adverse reactions, which may include cardiovascular, broncho-pulmonary, muco-cutaneous, neuro-psychosomatic and autonomic manifestations. Although nanomedicine-mediated triggering of complement activation has been suggested to be a significant contributing factor to these adverse events, complement activation may still proceed in non-responders. Whether these reactions share similar immunological mechanisms and underpinning genetic factors with drug hypersensitivity syndrome remains to be investigated. Genetic association studies could be a powerful tool to dissect causative factors and reveal the multiple molecular pathways that induce infusion related adverse reactions. It is envisaged that such research may lead to the design of reliable in vitro profiling tests for risk assessment and treatment decisions, thereby revolutionizing the practice of medicine with nanopharmaceuticals. Such procedures may further improve regulatory approval processes for nanomedicines currently in the pipeline and decrease the overall cost of health care. Here we discuss some key innate immunity genes and their polymorphisms in relation to nanomedicine infusion-mediated symptomatic responses.Display Omitted
Keywords: Acute allergic-like reactions; Anaphylatoxins; Complement system; C3a receptor; C5a receptor; Gene expression; Single nucleotide polymorphism
Nanotheranostics for personalized medicine
by Simona Mura; Patrick Couvreur (pp. 1394-1416).
The application of nanotechnology in the biomedical field, known as nanomedicine, has gained much interest in the recent past, as versatile strategy for selective drug delivery and diagnostic purposes. The already encouraging results obtained with monofunctional nanomedicines have directed the efforts of the scientists towards the creation of “nanotheranostics” ( i. e. theranostic nanomedicines) which integrate imaging and therapeutic functions in a single platform. Nanotheranostics hold great promises because they combine the simultaneous non-invasive diagnosis and treatment of diseases with the exciting possibility to monitor in real time drug release and distribution, thus predicting and validating the effectiveness of the therapy. Due to these features nanotheranostics are extremely attractive for optimizing treatment outcomes in cancer and other severe diseases. The following step is the attempt to use nanotheranostics for performing a real personalized medicine which will tailor optimized treatment to each patient, taking into account the individual variability. Clinical application of nanotheranostics would enable earlier detection and treatment of diseases and earlier assessment of the response, thus allowing screening for patients which would potentially respond to therapy and have higher possibilities of a favorable outcome. This concept makes nanotheranostics extremely appealing to elaborate personalized therapeutic protocols for achieving the maximal benefit along with a high safety profile. Among the several systems developed up to now, this review focuses on the nanotheranostics which, due to the promising results, show the highest potential of translation to clinical applications and may transform into concrete practice the concept of personalized nanomedicine.Display Omitted
Keywords: Theranostic; Nanomedicine; Drug delivery; Non invasive imaging; Cancer therapy; Cardiovascular disease; Personalized nanomedicine
Liposome imaging agents in personalized medicine
by Anncatrine L. Petersen; Anders E. Hansen; Alberto Gabizon; Thomas L. Andresen (pp. 1417-1435).
In recent years the importance of molecular and diagnostic imaging has increased dramatically in the treatment planning of many diseases and in particular in cancer therapy. Within nanomedicine there are particularly interesting possibilities for combining imaging and therapy. Engineered liposomes that selectively localize in tumor tissue can transport both drugs and imaging agents, which allows for a theranostic approach with great potential in personalized medicine. Radiolabeling of liposomes have for many years been used in preclinical studies for evaluating liposome in vivo performance and has been an important tool in the development of liposomal drugs. However, advanced imaging systems now provide new possibilities for non-invasive monitoring of liposome biodistribution in humans. Thus, advances in imaging and developments in liposome radiolabeling techniques allow us to enter a new arena where we start to consider how to use imaging for patient selection and treatment monitoring in connection to nanocarrier based medicines. Nanocarrier imaging agents could furthermore have interesting properties for disease diagnostics and staging. Here, we review the major advances in the development of radiolabeled liposomes for imaging as a tool in personalized medicine.Display Omitted
Keywords: Nanoparticles; Nanomedicine; Theranostics; Nanotheranostics; Nuclear imaging; Diagnostics; Radionuclides; SPECT; PET; Cancer
Immunomicelles for advancing personalized therapy
by Rupa R. Sawant; Aditi M. Jhaveri; Vladimir P. Torchilin (pp. 1436-1446).
Personalized medicine, which ultimately seeks to afford tailored therapeutic regimens for individual patients, is quickly emerging as a new paradigm in the diagnosis and treatment of diseases. The idea of casting aside generic treatments in favor of patient-centric therapies has become feasible owing to advances in nanotechnology and drug delivery coupled with an enhanced knowledge of genomics and an understanding of disease at the molecular level.This review highlights polymeric immunomicelles as a class of nanocarriers that have the potential to combine diagnosis, targeted drug therapy, as well as imaging and monitoring of therapeutic response, to render a personalized approach to the management of disease. Smart multi-functional immunomicelles, as the next generation of nanocarriers, are poised for facilitating personalized cancer treatment. This review provides an assessment of immunomicelles as tools for advancing personalized therapy of diseases, with cancer being the major focus.Display Omitted
Keywords: Personalized therapy; Targeted deliver; Polymeric micelles; Antibody-targeted; Immunomicelles; Imaging; Cancer; siRNA; Atherosclerotic plaques
Tumor-targeting multi-functional nanoparticles for theragnosis: New paradigm for cancer therapy
by Ju Hee Ryu; Heebeom Koo; In-Cheol Sun; Soon Hong Yuk; Kuiwon Choi; Kwangmeyung Kim; Ick Chan Kwon (pp. 1447-1458).
Theragnostic nanoparticles (NPs) contain diagnostic and therapeutic functions in one integrated system, enabling diagnosis, therapy, and monitoring of therapeutic response at the same time. For diagnostic function, theragnostic NPs require the inclusion of noninvasive imaging modalities. Among them, optical imaging has various advantages including sensitivity, real-time and convenient use, and non-ionization safety, which make it the leading technique for theragnostic NPs. For therapeutic function, theragnostic NPs have been applied to chemotherapy, photodynamic therapy, siRNA therapy and photothermal therapy. In this review, we present a recent progress reported in the development and applications of theragnostic NPs for cancer therapy. More specifically, we will focus on theragnostic NPs related with optical imaging, highlighting promising strategies based on optical imaging techniques.Display Omitted
Keywords: Theragnosis; Chemotherapy; Photodynamic therapy; siRNA therapy; Photothermal therapy; Optical imaging; Personalized medicine; Molecular imaging; Cancer; Nanomedicine
Molecular fabrications of smart nanobiomaterials and applications in personalized medicine
by Sotirios Koutsopoulos (pp. 1459-1476).
Recent advances in nanotechnology adequately address many of the current challenges in biomedicine. However, to advance medicine we need personalized treatments which require the combination of nanotechnological progress with genetics, molecular biology, gene sequencing, and computational design. This paper reviews the literature of nanoscale biomaterials described to be totally biocompatible, non-toxic, non-immunogenic, and biodegradable and furthermore, have been used or have the potential to be used in personalized biomedical applications such as drug delivery, tissue regeneration, and diagnostics. The nanobiomaterial architecture is discussed as basis for fabrication of novel integrated systems involving cells, growth factors, proteins, cytokines, drug molecules, and other biomolecules with the purpose of creating a universal, all purpose nanobiomedical device for personalized therapies. Nanofabrication strategies toward the development of a platform for the implementation of nanotechnology in personalized medicine are also presented. In addition, there is a discussion on the challenges faced for designing versatile, smart nanobiomaterials and the requirements for choosing a material with tailor made specifications to address the needs of a specific patient.Display Omitted
Keywords: Abbreviations; PLGA; Poly(lactic–co-glycolic acid); PEG; poly(ethylene glycol); ECM; extracellular matrix; RES; reticuloendothelial system; MMP; matrix metallo-proteinase; BBB; blood–brain-barrier; MRI; magnetic resonance imaging; PLA; poly(lactic acid); MSCs; mesenchymal stem cells; IGF-1; insulin-like growth factor-1; bFGF; basic fibroblast growth factorDrug delivery; Drug targeting; Pharmaceutical carriers; Tissue engineering; Tissue regeneration; Self assembly; Stimuli responsive materials
Reprogrammed cell delivery for personalized medicine
by Markus Wieland; Martin Fussenegger (pp. 1477-1487).
In most approaches, personalized medicine requires time- and cost-intensive characterization of an individual's genetic background in order to achieve the best-adapted therapy. For this purpose, cell-based drug delivery offers a promising alternative. In particular, synthetic biology has introduced the vision of cells being programmable therapeutic production facilities that can be introduced into patients. This review highlights the progress made in synthetic biology-based cell engineering toward advanced drug delivery entities. Starting from basic one-input responsive transcriptional or post-transcriptional gene control systems, the field has reached a level on which cells can be engineered to detect cancer cells, to obtain control over T-cell proliferation, and to restore blood glucose homeostasis upon blue light illumination. Furthermore, a cellular implant was developed that detects blood urate level disorders and acts accordingly to restore homeostasis while another cellular implant was engineered as an artificial insemination device that releases bull sperm into bovine ovarian only during ovulation time by recording endogenous luteinizing hormone levels. Soon, the field will reach a stage at which cells can be reprogrammed to detect multiple metabolic parameters and self-sufficiently treat any disorder connected to them.Display Omitted
Keywords: Synthetic biology; Gene circuit; Microencapsulation; Prosthetic network; Genetic switch
Personalized nanomedicine advancements for stem cell tracking
by Miroslaw Janowski; Jeff W.M. Bulte; Piotr Walczak (pp. 1488-1507).
Recent technological developments in biomedicine have facilitated the generation of data on the anatomical, physiological and molecular level for individual patients and thus introduces opportunity for therapy to be personalized in an unprecedented fashion. Generation of patient-specific stem cells exemplifies the efforts toward this new approach. Cell-based therapy is a highly promising treatment paradigm; however, due to the lack of consistent and unbiased data about the fate of stem cells in vivo, interpretation of therapeutic effects remains challenging hampering the progress in this field. The advent of nanotechnology with a wide palette of inorganic and organic nanostructures has expanded the arsenal of methods for tracking transplanted stem cells. The diversity of nanomaterials has revolutionized personalized nanomedicine and enables individualized tailoring of stem cell labeling materials for the specific needs of each patient. The successful implementation of stem cell tracking will likely be a significant driving force that will contribute to the further development of nanotheranostics. The purpose of this review is to emphasize the role of cell tracking using currently available nanoparticles.Display Omitted
Keywords: Nanoparticles; Transplantation; Stem cells; Imaging; Theranostics
RNAi-based nanomedicines for targeted personalized therapy
by Ala Daka; Dan Peer (pp. 1508-1521).
RNA interference (RNAi) has just made it through the pipeline to clinical trials. However, in order for RNAi to serve as an ideal personalized therapeutics and be clinically approved—safe, specific, and potent strategies must be devised for efficient delivery of RNAi payloads to specific cell types, which despite the immense potential, remains a challenge. Through evaluating the recent reported studies in this field, we introduce the progress in designing targeted nano-scaled strategies that are anticipated to overcome the delivery drawbacks and along with the exciting “omics” discipline to personalize RNAi-based therapeutics.Display Omitted
Keywords: Abbreviations; mAb; monoclonal antibody; ApoB; apolipoprotein B; BD; biodistribution; CME; clathrin-mediated endocytosis; CNT; carbon-nanotubes; DC-6-14; O; ,; O; ′-ditetradecanoyl-; N; -(α-trimethylammonioacetyl) diethanolamine chloride; DOPE; dioleoylphosphatidylethanolamine; DOTAP; N-[1-(2,3-dioleoyloxy)-propyl]-N,N,N-trimethylammonium methylsulfate; DOTMA; N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride; dsRNA; double stranded ribonucleic acid; EPR; enhanced permeability and retention; I.V.; intravenous; miRNA; micro ribonucleic acid; MPS; mononuclear phagocytic system; MW; molecular weight; NP; nanoparticle; nt; nucleotide; PEG; polyethylenglycol; PEI; Polyethyleneimine; PC; phosphatidylcholine; P.I.; post injection; PK; pharmacokinetics; RES; reticuloendothelial system; RISC; RNA-induced silencing complex; RNA; ribonucleic acid; shRNA; short hairpin ribonucleic acid; SNALP; stable lipid-nucleic acid particle; T; 1/2; half time; TLR; Toll-like receptorShort interfering RNA (siRNA); In vivo; Systemic delivery; Nanoparticles; Clinical trials; Personalized medicine
Nanoproteomics enabling personalized nanomedicine
by Claudio Nicolini; Nicola Bragazzi; Eugenia Pechkova (pp. 1522-1531).
Nucleic Acid Programmable Protein Arrays utilize a complex mammalian cell free expression system to produce proteins in situ. In alternative to fluorescent-labeled approaches a new label free method, emerging from the combined utilization of three independent and complementary nanotechnological approaches, appears capable to analyze protein function and protein–protein interaction in studies promising for personalized medicine. Quartz Micro Circuit nanogravimetry, based on frequency and dissipation factor, mass spectrometry and anodic porous alumina overcomes indeed the limits of correlated fluorescence detection plagued by the background still present after extensive washes. This could be further optimized by a homogeneous and well defined bacterial cell free expression system capable to realize the ambitious objective to quantify the regulatory protein networks in humans. Implications for personalized medicine of the above label free protein array using different test genes proteins are reported.Display Omitted
Keywords: QMC_F; QMC_D; MS; APA; Leader Genes; NAPPA
Epigenetics advancing personalized nanomedicine in cancer therapy
by Shujun Liu (pp. 1532-1543).
Personalized medicine aims to deliver the right drug to a right patient at the right time. It offers unique opportunities to integrate new technologies and concepts to disease prognosis, diagnosis and therapeutics. While selective personalized therapies are conceptually impressive, the majority of cancer therapies have dismal outcome. Such therapeutic failure could result from no response, drug resistance, disease relapse or severe side effect from improper drug delivery. Nanomedicine, the application of nanotechnology in medicine, has a potential to advance the identification of diagnostic and prognostic biomarkers and the delivery of right drug to disease sites. Epigenetic aberrations dynamically contribute to cancer pathogenesis. Given the individualized traits of epigenetic biomarkers, epigenetic considerations would significantly refine personalized nanomedicine. This review aims to dissect the interface of personalized medicine with nanomedicine and epigenetics. I will outline the progress and highlight challenges and areas that can be further explored perfecting the personalized health care.True sense of personalized nanomedicine. The uniqueness of patients' environmental and intrinsic stimuli makes individualized epigenetic signatures, which reciprocally determine the pattern of epigenetic and genetic alterations. The combination of both epigenetic and genetic attributes provides individual diagnostic and prognostic biomarkers informing the treatment plans. Nanotechnology can advance the identification of biomarkers and deliver the drug to the disease sites, whose application will increase the therapeutic window of personalized medicine. The coalition of personalized nanomedicine with individualized epigenetic information will accomplish the best health care.Display Omitted
Keywords: Abbreviations; 5mC; 5-methylcytosine; 5hmC; 5-hydroxymethylcytosine; ABC; adenosine 5′-triphosphate-binding cassette; AML; acute myeloid leukemia; ATP; adenosine 5′-triphosphate; BCR; breakpoint cluster region; BRCA1; breast cancer type 1; CBFβ; core binding factor β; CBP; CREB binding protein; CML; chronic myelogenous leukemia; CREB; cAMP response element-binding; DNMT; DNA methyltransferase; DOX; doxorubicin; EGFR; epidermal growth factor receptor; ER; estrogen receptor; ErbB2; v-erb-b2 erythroblastic leukemia viral oncogene homolog 2; ETO; eight-twenty-one; FHIT; fragile histidine triad; FLT3; fms-like tyrosine kinase receptor-3; GSTP1; glutathione S-transferase gene; HAT; histone acetylase; HDAC; histone deacetylase; HDMT; histone demethyltransferase; HER2; human epidermal growth factor receptor 2; HGP; Human Genome Project; HMT; histone methyltransferase; IDH; isocitrate dehydrogenase; IL-3; interleukin 3; MDS; myelodysplastic syndrome; miRs; microRNAs; MOZ; monocytic leukemia zinc finger; MRI; magnetic resonance imaging; MZ; monozygotic; PI3K; phosphatidylinositol 3-kinase; PZLF; promyelocytic leukemia zinc-finger protein; RAR-α; retinoic acid receptor alpha; RASSF1A; Ras-association domain family 1A gene; SAM; S-adenosyl-methionine; SMMHC; smooth muscle myosin heavy chain; SNPs; single-nucleotide polymorphisms; TET; ten-eleven-translocation; TSGs; tumor suppressor genes; UTRs; untranslated regions; VMRs; variably methylated regions; WWOX; WW-domain containing oxidoreductaseEpigenetics; Biomarkers; Targeted therapy; Nanotechnology; Nanoparticles; Drug delivery; Personalized medicine; Nanomedicine; Personalized nanomedicine
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