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Book RNA Delivery Function for Anticancer Therapeutics

Download or read book RNA Delivery Function for Anticancer Therapeutics written by Loutfy H. Madkour and published by CRC Press. This book was released on 2022-01-25 with total page 424 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book presents an overview of the current status of translating the RNAi cancer therapeutics in the clinic, a brief description of the biological barriers in drug delivery, and the roles of imaging in aspects of administration route, systemic circulation, and cellular barriers for the clinical translation of RNAi cancer therapeutics, and with partial content for discussing the safety concerns. It then focuses on imaging-guided delivery of RNAi therapeutics in preclinical development, including the basic principles of different imaging modalities, and their advantages and limitations for biological imaging. With growing number of RNAi therapeutics entering the clinic, various imaging methods will play an important role in facilitating the translation of RNAi cancer therapeutics from bench to bedside. RNAi technique has become a powerful tool for basic research to selectively knock down gene expression in vitro and in vivo. Our scientific and industrial communities have started to develop RNAi therapeutics as the next class of drugs for treating a variety of genetic disorders, such as cancer and other diseases that are particularly hard to address with current treatment strategies. Key Features Provides insight into the current advances and hurdles of RNAi therapeutics. Accelerates RNAi, miRNAs, and siRNA drug development for cancer therapy from bench to bedside. Addresses various modifications and novel delivery strategies for miRNAs, piRNAs and siRNA delivery in anticancer therapeutics. Explores the need for the interaction of hematologists,cell biologists, immunologists, and material scientists in the development of novel cancer therapies. Describes the current status of clinical trials related to miRNA and siRNA-based cancer therapy Presents remaining issues that need to be overcome to establish successful therapies.

Book Nucleic Acids as Gene Anticancer Drug Delivery Therapy

Download or read book Nucleic Acids as Gene Anticancer Drug Delivery Therapy written by Loutfy H. Madkour and published by Academic Press. This book was released on 2019-08-27 with total page 650 pages. Available in PDF, EPUB and Kindle. Book excerpt: Nucleic Acids as Gene Anticancer Drug Delivery Therapy highlights the most recent developments in cancer treatment using nucleic acids, nanoparticles and polymer nanoparticles for genomic nanocarriers as drug delivery, including promising opportunities for targeted and combination therapy. The development of a wide spectrum of nanoscale technologies is beginning to change the scientific landscape in terms of disease diagnosis, treatment, and prevention. This book presents the use of nanotechnology for medical applications, focusing on its use for anticancer drug delivery. Various intelligent drug delivery systems such as inorganic nanoparticles and polymer-based drug delivery are discussed. The use of smart drug delivery systems seems to be a promising approach for developing intelligent therapeutic systems for cancer immunotherapies and is discussed in detail along with nucleic acid-targeted drug delivery combination therapy for cancer. Nucleic Acids as Gene Anticancer Drug Delivery Therapy will be a useful reference for pharmaceutical scientists, pharmacologiests, and those involved in nanotechnology and cancer research. Discusses intelligent drug delivery systems such as inorganic nanoparticles and polymer-based drug delivery Contains a comprehensive comparison of various delivery systems, listing their advantages and limitations Presents combination therapy as a new hope for enhancing current gene-based treatment efficacy

Book RNA Therapeutics

    Book Details:
  • Author : Paloma H. Giangrande
  • Publisher : Academic Press
  • Release : 2022-04-10
  • ISBN : 0128217391
  • Pages : 474 pages

Download or read book RNA Therapeutics written by Paloma H. Giangrande and published by Academic Press. This book was released on 2022-04-10 with total page 474 pages. Available in PDF, EPUB and Kindle. Book excerpt: RNA Therapeutics: The Evolving Landscape of RNA Therapeutics provides a comprehensive overview of RNA therapeutic modalities, from bench-to-bedside, with an emphasis on the increasingly impactful areas of gene therapy, oligonucleotide therapeutics, gene editing and delivery. International leaders in the field examine RNA-based therapeutics tools that have been developed to-date to modulate cellular processes such as transcription, translation and protein function. Approved RNA-based therapies and lessons learned from failed therapies are discussed in-depth, as are evolving advances in RNA biochemical analysis, and similar advances that are enabling clinical application of RNA-based therapies. Later sections discuss delivery technologies, remaining hurdles in research and translation, the therapy development process from the lab to the clinic, and novel RNA-based therapies currently in development. Features leading experts in the field of RNA therapeutics, spanning all classes of RNA therapies Provides a detailed examination of approved RNA therapies and lessons learned from failed therapeutics Covers all aspects of therapeutic discovery and preclinical development, as well as clinical translation, manufacturing and regulatory aspects

Book Advanced Delivery and Therapeutic Applications of RNAi

Download or read book Advanced Delivery and Therapeutic Applications of RNAi written by Kun Cheng and published by John Wiley & Sons. This book was released on 2013-04-19 with total page 660 pages. Available in PDF, EPUB and Kindle. Book excerpt: Commonly used by researchers to develop technologies for modifying and studying genetic process, RNA interference (RNAi) has many potential uses in medicine, biotechnology, and functional genomics. This book covers all essential aspects involved in the development of RNAi therapeutics, providing detailed guidance on the challenges and opportunities of bringing RNAi technologies from bench to clinic. It explores the design and mechanism of RNAi molecules, delivery strategies, and therapeutic applications in various diseases. Preclinical, regulatory, market, and intellectual aspects of RNAi technologies are also covered.

Book Advanced Drug Delivery Systems in the Management of Cancer

Download or read book Advanced Drug Delivery Systems in the Management of Cancer written by Kamal Dua and published by Elsevier. This book was released on 2021-06-24 with total page 572 pages. Available in PDF, EPUB and Kindle. Book excerpt: Advanced Drug Delivery Systems in the Management of Cancer discusses recent developments in nanomedicine and nano-based drug delivery systems used in the treatment of cancers affecting the blood, lungs, brain, and kidneys. The research presented in this book includes international collaborations in the area of novel drug delivery for the treatment of cancer. Cancer therapy remains one of the greatest challenges in modern medicine, as successful treatment requires the elimination of malignant cells that are closely related to normal cells within the body. Advanced drug delivery systems are carriers for a wide range of pharmacotherapies used in many applications, including cancer treatment. The use of such carrier systems in cancer treatment is growing rapidly as they help overcome the limitations associated with conventional drug delivery systems. Some of the conventional limitations that these advanced drug delivery systems help overcome include nonspecific targeting, systemic toxicity, poor oral bioavailability, reduced efficacy, and low therapeutic index. This book begins with a brief introduction to cancer biology. This is followed by an overview of the current landscape in pharmacotherapy for the cancer management. The need for advanced drug delivery systems in oncology and cancer treatment is established, and the systems that can be used for several specific cancers are discussed. Several chapters of the book are devoted to discussing the latest technologies and advances in nanotechnology. These include practical solutions on how to design a more effective nanocarrier for the drugs used in cancer therapeutics. Each chapter is written with the goal of informing readers about the latest advancements in drug delivery system technologies while reinforcing understanding through various detailed tables, figures, and illustrations. Advanced Drug Delivery Systems in the Management of Cancer is a valuable resource for anyone working in the fields of cancer biology and drug delivery, whether in academia, research, or industry. The book will be especially useful for researchers in drug formulation and drug delivery as well as for biological and translational researchers working in the field of cancer. Presents an overview of the recent perspectives and challenges within the management and diagnosis of cancer Provides insights into how advanced drug delivery systems can effectively be used in the management of a wide range of cancers Includes up-to-date information on diagnostic methods and treatment strategies using controlled drug delivery systems

Book RNA Therapeutics

    Book Details:
  • Author : Mouldy Sioud
  • Publisher : Humana
  • Release : 2016-08-23
  • ISBN : 9781493961511
  • Pages : 526 pages

Download or read book RNA Therapeutics written by Mouldy Sioud and published by Humana. This book was released on 2016-08-23 with total page 526 pages. Available in PDF, EPUB and Kindle. Book excerpt: Central to the synthesis of proteins, the performance of catalysis, and many other physiological processes, the aberrant expression of which can be linked to human diseases including cancers, RNA has proven to be key target for therapeutics as well as a tool for therapy. In RNA Therapeutics: Function, Design, and Delivery, expert contributors from a broad spectrum of scientific backgrounds highlight the roles that messenger RNAs and small RNAs can play in biology and medicine. While covering the five major RNA-based drugs, namely the use of ribozymes to cleave and/or correct mRNA transcript, the use of siRNA for targeted silencing of gene transcripts, the use of aptamers, like short RNA molecules, for neutralizing the protein functions, the use mRNA-transfected DCs to activate immune system against tumor cells, as well as the use of RNA to reprogram T and/or DC cell function, this extensive volume brings together the fields of coding (mRNA) and non-coding RNA such as ribozymes, RNAse P, siRNAs, and miRNAs into one convenient source. Written in the highly successful Methods in Molecular BiologyTM series format, the cutting-edge protocol chapters contain introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and practical tips on troubleshooting and avoiding known pitfalls. Also, the book contains several excellent reviews for teaching purposes. Authoritative and comprehensive, RNA Therapeutics: Function, Design, and Delivery provides key models and tools which will assist researchers in increasing our understanding of RNA functions, modifications, and their involvement in diseases in order to lead to the design of vital new RNA-based therapeutics.

Book Therapeutic Oligonucleotides

Download or read book Therapeutic Oligonucleotides written by Jens Kurreck and published by Royal Society of Chemistry. This book was released on 2008 with total page 362 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides a compelling overall update on current status of RNA interference

Book RNA Nanoparticle as a Safe and Effective Drug Delivery Platform for Cancer Therapy

Download or read book RNA Nanoparticle as a Safe and Effective Drug Delivery Platform for Cancer Therapy written by Sijin Guo and published by . This book was released on 2019 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Ribonucleic acid (RNA) nanotechnology is a rapidly emerging field that focuses on the nanostructure design, construction, and application in biotechnology and biomedicine. Unlike other biomacromolecules, RNA is more flexible in structure and more versatile in functionality. On the other hand, RNA is a naturally-occurring biopolymer, making them more biocompatible compared to other nanomaterials. Thus, RNA can serve as a building block to construct nanoparticles as drug delivery platform for cancer therapy. This dissertation primarily describes a fundamental study that explores the immune-compatibility of RNA nanoparticles, as well as the use of thermostable RNA nanoparticles to specifically deliver therapeutics for efficient cancer therapy without causing toxicity. Firstly, RNA polygons that have identical size but varying shapes, or same shape but with different sizes were constructed as study model. The RNA nanoparticles were found to be immunologically inert, indicating that RNA nanoparticles are safe drug carriers without triggering immune responses. On the other hand, they can elicit significant immunomodulation by extending the nanoparticles with special sequences. Specifically, this immunomodulation was found to be size, shape, sequence-dependent, demonstrating the potential of using RNA nanoparticles in immunotherapy. Secondly, the use of a thermostable RNA nanoparticle for solubilizing and high-density loading chemotherapeutic drugs for cancer inhibition is reported. Small chemotherapeutic drugs possess significant anti-cancer activity, but their clinical applications were greatly limited by the poor biocompatibility such as water-insolubility. By chemically conjugating water-insoluble drugs to RNA, the RNA nanoparticles dramatically improved drug water-solubility. An ultra-thermostable RNA four-way junction nanoparticle was able to covalently load twenty-four copies of paclitaxel without nanoparticle dissociation or unfolding. After intravenous administration, the resulting RNA-paclitaxel nanoparticles harboring specific cancer targeting ligand significantly inhibited breast cancer tumor in mice. The toxicity in organs and immune responses in mice were almost undetectable. Besides paclitaxel, this RNA-drug conjugation was applied to another anti-cancer drug, camptothecin, and showed significant inhibitory effect on tumor growth. Furthermore, an acid labile linker was developed within RNA-drug conjugates, aiming at controlling pH-responsive drug release in acidic tumor environment to improve drug efficacy. Thirdly, a three-dimensional RNA cube was constructed and explored as a multi-functional drug carrier by incorporation with different therapeutic modules. This multi-functional RNA cube is able to load chemotherapeutic drug, immunostimulatory molecule, or short-interfering RNA for enhanced cellular effects in vitro. What’s more, the RNA cube can be manipulated to become reconfigurable, suggesting the great potential of drug encapsulation and release for in vivo applications. Collectively, these findings demonstrate that RNA nanoparticles can serve as a biocompatible drug delivery platform for effective cancer therapy with favorable safety profile.

Book RNA Nanotechnology and Therapeutics

Download or read book RNA Nanotechnology and Therapeutics written by Peixuan Guo and published by CRC Press. This book was released on 2022-07-18 with total page 644 pages. Available in PDF, EPUB and Kindle. Book excerpt: Interest in RNA nanotechnology has increased in recent years as recognition of its potential for applications in nanomedicine has grown. Edited by the world's foremost experts in nanomedicine, this comprehensive, state-of-the-art reference details the latest research developments and challenges in the biophysical and single molecule approaches in RNA nanotechnology. In addition, the text also provides in-depth discussions of RNA structure for nanoparticle construction, RNA computation and modeling, single molecule imaging of RNA, RNA nanoparticle assembly, RNA nanoparticles in therapeutics, immunorecognition of RNA nanomaterials, RNA chemistry for nanoparticle synthesis, and conjugation and labeling. Presents the latest research and discoveries in RNA nanotechnology Features contributions from world-class experts in the field Covers RNA nanoparticles in therapeutics Describes self-assembled RNA nanoparticles

Book Nanopharmaceuticals  Principles and Applications Vol  3

Download or read book Nanopharmaceuticals Principles and Applications Vol 3 written by Vinod Kumar Yata and published by Springer Nature. This book was released on 2020-08-19 with total page 340 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is the third volume on this subject and focuses on the recent advances of nanopharmaceuticals in cancer, dental, dermal and drug delivery applications and presents their safety, toxicity and therapeutic efficacy. The book also includes the transport phenomenon of nanomaterials and important pathways for drug delivery applications. It goes on to explain the toxicity of nanoparticles to different physiological systems and methods used to assess this for different organ systems using examples of in vivo systems.

Book Messenger RNA Therapeutics

Download or read book Messenger RNA Therapeutics written by Stefan Jurga and published by Springer Nature. This book was released on 2022-09-20 with total page 451 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book focuses on the fundamentals and applications of messenger RNA (mRNA)-based therapeutics and discusses the strengths and key challenges of this emerging class of drugs. In the past 30 years, extensive research and technological development in many areas have contributed to the emergence of in vitro transcribed mRNA as a therapeutic that has now reached clinical testing. Formulations that protect the mRNA from nucleases and accelerate its cellular uptake, combined with improvements to the mRNA molecules themselves, have been critical advancements for mRNAs to become viable therapeutics. Though once regarded as a serious impediment, the transient nature of mRNA technology is now considered a major advantage in making mRNA therapies safe and, ultimately, a potential game changer in the field of medicine. This new book in the RNA Technologies series provides a state-of-the-art overview on the emerging field of mRNA therapeutics covering essential strategies for formulation, delivery, and application. It also reviews the promising role in cancer immunotherapy, respiratory diseases, and chronic HBV infection and discusses RNA vaccines in light of the current COVID-19 pandemic. mRNA-based approaches have great potential to revolutionize molecular biology, cell biology, biomedical research, and medicine. Thus, this handbook is an essential resource for researchers in academia and industry contributing to the development of this new area of therapeutics.

Book Drug Delivery of SiRNA Therapeutics

Download or read book Drug Delivery of SiRNA Therapeutics written by Gaetano Lamberti and published by . This book was released on 2020-06-15 with total page 286 pages. Available in PDF, EPUB and Kindle. Book excerpt: The new frontier of pharmaceutical sciences is gene therapy, which is the use of molecules able to interact directly with the expression of the genetic material of the patient as well as of the disease-causing guest (bacteria, virus, parasites, and tumor cells). Among the molecules of interest for gene therapy, a relevant role is played by small interfering RNA (siRNA) molecules able to interfere with the expression of genes of interest for some diseases. However, siRNA molecules, even if they are powerful as drugs, are difficult to deliver since they are sensitive to enzymes present in plasma and they are large and negatively charged, so are difficult to administer into the cell nuclei, since the cell walls are scarcely permeable to large molecules and are also negatively charged. Therefore, the focus of research on siRNA-based therapies is their delivery, which can be performed by chemical modification, association with aptamers or polycations, or embedding them into properly designed liposomes. This book is centered on the more recent development in siRNA delivery techniques toward the clinical applications of this potent class of drugs.

Book RNA Interference from Biology to Therapeutics

Download or read book RNA Interference from Biology to Therapeutics written by Kenneth A. Howard and published by Springer Science & Business Media. This book was released on 2012-10-19 with total page 348 pages. Available in PDF, EPUB and Kindle. Book excerpt: The enormous potential of siRNA as a therapeutic has led to an explosion of interest from the scientific community. There has been intense interest from Big Pharma to capitalise on this new technology but the fact remains that delivery is a key determinant in realizing the full clinical potential of RNA interference. There is an urgent need for better delivery methods to take this technology forward. This book addresses the role of different RNAi molecules in cellular processes as rational for diagnostic and therapeutic approaches. This book will cover RNAi therapeutic design to optimize siRNA potency and reduce off-target effects and current delivery technologies to overcome both intracellular and extracellular barriers. The reader will gain an insight into RNA interference from the cellular mechanisms to screening to siRNA design right through to diagnostic and therapeutic applications.

Book Nano Oncologicals

    Book Details:
  • Author : Maria José Alonso
  • Publisher : Springer
  • Release : 2014-10-15
  • ISBN : 3319080849
  • Pages : 478 pages

Download or read book Nano Oncologicals written by Maria José Alonso and published by Springer. This book was released on 2014-10-15 with total page 478 pages. Available in PDF, EPUB and Kindle. Book excerpt: This authoritative volume focuses on emerging technologies in cancer nano medicine, characterized by their multi-functionality and potential to address simultaneously diverse issues of clinical relevance in the treatment of cancer. The book consists of sixteen chapters divided into six sections: 1) Biological Barriers in Cancer; 2) Tumor Targeting; 3) Targeting the Immune System; 4) Gene Therapy; 5) Nano theranostics and 6) Translational Aspects of Nano-Oncologicals. The volume starts with an introduction describing the biological barriers associated with cancer therapy and highlighting ways to overcome such barriers through the use of nanotechnology. This is followed by an analysis of the two major targeting strategies currently under investigation in cancer therapy: namely, the targeting of cancer cells and the targeting of the immune system. In the first case, the book presents liposomal and polymer-based therapies, including photodynamic approaches. In the second case, it analyzes in detail the possibility of either improving the efficiency of the immune system toward preventing cancer progression (cancer immunomodulation) or generating responses against specific cancer antigens (cancer vaccines). Beyond these targeting options, Nano-Oncologicals: New Targeting and Delivery Approaches presents the most recent technological advances in the area of nucleic acid-based therapies, along with those in the area of theranostics, where the design of multifunctional nano carriers becomes vital. Following the study of the most promising nanotechnologies around the development of nano-oncologicals, the book ends with an overview of regulatory and toxicological issues, which are critical in their translational pathway, and the presentation of a nucleic acid-based therapy case-study. This book is an important resource for scientists interested in the design and development of anticancer nanotechnologies and also to those aiming to push their technology through clinical development.

Book Development of Thermostable RNA Nanoparticles as Drug Delivery Platform for Cancer Treatment

Download or read book Development of Thermostable RNA Nanoparticles as Drug Delivery Platform for Cancer Treatment written by Xin Li (Pharmaceutical scientist) and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Ribonucleic acid (RNA) nanotechnology is the development and application of nanoparticles whose main component is RNA. Due to the unique advantages of RNA nanoparticles, they have been used as drug delivery platforms of small molecule drugs and therapeutic oligos for various types of cancer treatment. This dissertation mainly describes the construction, characterization, and application of thermostable RNA nanoparticles with various size and shape to deliver different types of small molecule anticancer drugs. Firstly, a series of RNA dendrimers was constructed using 3WJs with different thermostability as the building block, which demonstrated temperature triggered layer-by-layer release property. RNA dendrimer was then functionalized with paclitaxel as anticancer drug and folate as targeting ligand, which showed cancer targeting and inhibition effect. Furthermore, due to the branched structure and negative charge, RNA dendrimer has a unique shielding effect which prevents the interaction between its loaded cargos with surrounding proteins or cell membranes. Secondly, 4WJ RNA nanoparticle with high thermostability and drug loading capacity has been constructed to solubilize and deliver SN38, which is a highly potent anticancer drug whose clinical application is limited by its low stability and solubility. Conjugation of SN38 to RNA strands significantly increased its water solubility and enables it to be dissolved in aqueous solution. 4WJ RNA nanoparticles functionalized with SN38 and RNA aptamer showed promising tumor inhibition effect in both colorectal cancer cell line and xenograft mouse model. Thirdly, 4WJ RNA nanoparticles were incorporated with another type of anticancer drug, nucleoside analogue, through one step RNA synthesis without further conjugation and purification. RNA nanoparticles incorporated with floxuridine and gemcitabine demonstrated tumor suppression effect in colorectal cancer and breast cancer, respectively. Moreover, the multivalency and programmability enables the combinational chemotherapy with precise control over the quantity and ratio of combined drugs to achieve synergistic effect and overcome drug resistance. RNA nanoparticles loaded with gemcitabine together with floxuridine, paclitaxel, and SN38, respectively, has been constructed and demonstrated improved cytotoxicity to cancer cells comparing with monotherapy. Lastly, globular RNA nanoparticles with the shape of 4WJ – 8WJ were constructed which demonstrated high thermostability. Collectively, RNA nanoparticles are a highly stable and programmable platform which show great potential to targeted deliver various kinds of small molecule drugs with distinct physicochemical, pharmacological, and pharmacokinetic properties for cancer treatment.

Book RNA Nanotechnology

    Book Details:
  • Author : Bin Wang
  • Publisher : CRC Press
  • Release : 2014-04-02
  • ISBN : 9814411647
  • Pages : 468 pages

Download or read book RNA Nanotechnology written by Bin Wang and published by CRC Press. This book was released on 2014-04-02 with total page 468 pages. Available in PDF, EPUB and Kindle. Book excerpt: In the past few decades there has been incredible growth in "bionano"-related research, which has been accompanied by numerous publications in this field. Although various compilations address topics related to deoxyribonucleic acid (DNA) and protein, there are few books that focus on determining the structure of ribonucleic acid (RNA) and using RNA as building blocks to construct nanoarchitectures for biomedical and healthcare applications. RNA Nanotechnology is a comprehensive volume that details both the traditional approaches and the latest developments in the field of RNA-related technology. This book targets a wide audience: a broad introduction provides a solid academic background for students, researchers, and scientists who are unfamiliar with the subject, while the in-depth descriptions and discussions are useful for advanced professionals. The book opens with reviews on the basic aspects of RNA biology, computational approaches for predicting RNA structures, and traditional and emerging experimental approaches for probing RNA structures. This section is followed by explorations of the latest research and discoveries in RNA nanotechnology, including the design and construction of RNA-based nanostructures. The final segment of the book includes descriptions and discussions of the potential biological and therapeutic applications of small RNA molecules, such as small/short interfering RNAs (siRNAs), microRNAs (miRNAs), RNA aptamers, and ribozymes.

Book Novel Approaches for Targeted Delivery of Cancer Therapeutics to Nuclei of Malignant Cells

Download or read book Novel Approaches for Targeted Delivery of Cancer Therapeutics to Nuclei of Malignant Cells written by Animikh Ray and published by . This book was released on 2016 with total page 190 pages. Available in PDF, EPUB and Kindle. Book excerpt: The primary goal of this project is to increase specific uptake of anti-cancer therapeutics by nuclei of cancer cells. A lot of research has been done to target therapeutics specifically across plasma membrane of malignant cells. However not much research has been done to deliver them to their target cellular compartment where the drug elicits its pharmacological response. In case of majority of anti-cancer drugs the target is usually nuclei of cancer cells. Hence nuclear delivery of therapeutics is the next frontier of pharmaceutics. In this dissertation work this issue has been investigated. Initially in the first strategy adopted, novel peptide prodrug of doxorubicin was developed which may evade over-expressed efflux pumps on breast cancer cells. This approach may lead to increased uptake and higher drug accumulation in nuclei of cancer cells. L-val-L-val doxorubicin prodrug was synthesized following standard f-moc chemistry. The prodrug was analyzed for stability, cellular and nuclear uptake and interaction with efflux and peptide transporters. Breast cancer cells (T-47D) were grown on polystyrene 12-well plates. The prodrug Val-Val-doxorubicin was found to be very stable in breast cancer cell homogenate. It was able to evade efflux pumps. The prodrug penetrated cytoplasm and nuclei of cancer cells by interacting with peptide transporters over-expressed on plasma and nuclear membrane of T-47D.Uptake of prodrug was found to be 10 fold higher than parent drug. Peptide prodrug derivatization of doxorubicin has potential to evade efflux pumps and increase availability and nuclear accumulation of doxorubcin in breast cancer cells. However due to its stability the prodrug did not biorevert to its parent drug in therapeutic concentration. Hence alternative approaches were investigated. As part of this alternate approach novel nuclear localization signal (NLS) peptide analogues have been designed that can carry therapeutic molecules specifically into nuclei of cancer cells. This strategy might be able to reduce toxicity to non-malignant cells by delivering anticancer drugs to subcellular organelle i.e. nucleus of cancer cells preferentially. Native NLS peptide-conjugated drugs can reach nucleus of any cell non-specifically. However the overarching challenge is to enhance drug uptake across plasma and nuclear membranes to enhance anticancer drug delivery in drug resistant cancer cells. Adenoviral fiber protein (AFP) that encodes for NLS has been known to penetrate both plasma and nuclear membrane nonspecifically. Therefore novel NLS peptide analogues have been synthesized by substitutions of NLS sequence specific amino acids for targeting cancer cells primarily. Specific amino acids of native NLS have been substituted based on hydrophobic interactions between the peptides with plasma membrane and nucleo pore complex (NPC) that can influence cytoplasmic and nuclear transport. These peptides can carry therapeutics selectively to nuclei of cancer cells simultaneously evading normal cells. Five NLS peptides have been synthesized. These peptides were synthesized by AAPtech automated peptide synthesizer. Following synthesis, the peptides were purified by a shimadzu Preparative HPLC which was confirmed by HPLC-MSMS. Confocal and quantitative uptake studies with various cancer and corresponding non-cancerous human cell lines were performed. It was observed that two (NLS3 and NLS5) peptides are specific for targeting cancer cell nucleus. It has led to an unequivocal conclusion that these novel peptide analogues can selectively bind to plasma membranes of cancer cells and target NPC simultaneously. Following screening of peptides which can function as targeting moieties, nanoparticle formulation was developed to deliver anti-cancer drugs. One of the important parameters for nuclear drug delivery is size. The nucleopore complex has a diameter of 30 nm. Cargo with 30-40 nm can enter the NPC passively. However particles higher than 40 nm need to be actively transported across NPC. It has been reported that particles with 60-70 nm with anti cancer drugs can be delivered into nucleus with localization signals. This is the target size which has been achieved for doxorubicin loaded nanoparticle. PLGA-PEG-NH2 was used as polymer for preparation of doxorubicin loaded nanoparticles. This is because of availability of NH2 group at the end of PEG group for conjugation of peptide moiety for targeted delivery following optimization of size. Nanoparticles were prepared by nanoprecipitation method. Parameters like effect of solvent, polymer concentration, effect of aqueous phase volume, drug concentration were optimized to yield a nanoparticle of size range 60-70 nm as this size can be taken up by nucleus if actively aided by nuclear localization signal. Following preparation of nanoparticle of optimized size, screened peptides (NLS3 and NLS5) with maximum affinity for cancer cell nuclei with minimal entry into corresponding non-malignant cells were conjugated to nanoparticles. Targeted nanoparticles were investigated for its active targeting property in a 3D model of breast cancer. It was observed that nanoparticle with NLS conjugated to its surface delivered higher concentration of doxorubicin compared to unconjugated nanoparticle or free doxorubicin.