There is an increasing interest in the scientific international community to exploit nanodevices for the delivery of drugs. Indeed, it is now generally accepted that nanomedicine may significantly improve the therapeutic index of many drugs by: (1) protecting the drug from the dcgradation/metabolization; (2) promoting drug transport through biological barriers (i.e., endothclia and epithelia); (3) increasing the intracellular diffusion of many drugs with poor intracellular penetration; (4) controlling the drug release; and (5) targeting the diseased area, therefore increasing the pharmacological activity and decreasing the drug's side effects and toxicity.
Since the toxicological issue represents the major limitation of most of the anti-cancer drugs, it is not surprising that many nanomedicines currently on the market are related to the oncology field (i.e., Doxil~®, Abraxane~®, etc.). To deliver therapeutic agents to tumor cells in vivo, one must overcome the problems of drug resistance at the tumor level because of physiological barriers (noncellular-based mechanisms), drug resistance at the cellular level (cellular mechanisms), and distribution, biotransformation, and clearance of anticancer drugs in the body. The academic research has highlighted that some nanomedicine formulations may overcome various anticancer drug resistance mechanisms (i.e., multidrug resistance, inhibition of nucleoside transporters, etc.) which represent an important medical need. In this view, some nanodrugs have actually reached the phase III clinical trials, like Livatag~® for treatment of the resistant hepatocarcinoma. Other approaches, albeit less advanced, include the development of multifunctional nanoparticles combining both therapeutic and imaging functionalities or even nanodevices containing two or more drugs oriented toward different cancer targets (i.e., tumor vasculature and cancer cells). The above considerations illustrate the important contribution of nanomedicines in oncology.
Nano-Oncologicals: New Targeting and Delivery Approaches, edited by Professor Maria Jose Alonso and Professor Marcos Garcia-Fuentes, represents an important and complete piece of information on the more advanced research and applications in the nano-oncological field. Overcoming the biological barriers for optimizing anticanccr drug delivery in tumors is an important challenge that can be addressed by taking advantage of the enhanced permeability and retention (EPR) effect. But inside of the tumor tissue, nano-sized exosome vesicles that are capable of transferring intracellular proteins or nucleic acids contents to the tumoral micro-environment may also represent a promising strategy to deliver antitumor agents to target cancer cells. This is explained in the first part of the book, "Biological Barriers in Cancer." The second part answers the major question of how to efficiently target the tumor tissue by using either polymer nanoparticles, liposomes or micelles, whereas a special chapter deals with the use of nanocarriers for photodynamic therapy. Apart from the use of conventional chemotherapy, researchers have also studied new strategies to enhance the immune response against cancer, including antigen-pulsed dendritic cells, recombinant DNA and viral vaccines, and a number of novel immune adjuvants targeting immune competent cells. In this view, the application of nanotechnology to immunosuppression or immunomodulation also represents a powerful tool to improve cancer immunotherapy and is discussed in detail in the third part of this book.
The following part deals with the use of small interfering RNA (siRNA) or microRNA (miRNA) as a tumor suppressor, when deletions or mutations occur in diverse human malignancies. However, since the delivery of these small therapeutic nucleic acids remains a major challenge because of enzymatic degradation and poor intracellular penetration, the use of polymeric micelles, liposomes, or nanoparticles provides a decisive advantage over the administration of those biomacromolecules in an aqueous solution. The efficient combination of a therapeutic agent with an imaging molecule in a single nanomedicine and the extreme versatility of the nano-theranostic platform could contribute to the development of individualized treatment protocols offering the opportunity for personalized nanomedicine. This is nicely addressed in the fifth part of the book, with a complete overview on the impressive progresses of nano-based approaches for diagnosis, imaging, and therapy of cancers with many illustrative examples arising from recent literature. Two other chapters are focused on more specific nanotheranostic systems made of multifunctional gold nanoparticles or microbubbles. The last part of the book discusses the conditions for the translation of anticancer nanomedicines into the clinic, including the toxicologi-cal issues and other important regulatory aspects. Finally, a case study is given concerning a new double-strand RNA-based nanocomplex with potent anticancer activity.
This book assembles the major aspects of nano-oncology. It represents an essential reference to a broad scientific community, including physico-chemists, pharmaceutical technologists, pharmacologists, oncologists, and biomedical scientists in general. I hope that this contribution to the drug delivery field will give rise to positive discussions between all scientists, regardless of their age, position, or experience. Villebon-sur-Yvette, France Patrick Couvreur

Part I Biological Barriers in Cancer

1 Passive vs. Active Targeting: An Update of the EPR Role in Drug Delivery to Tumors 3

2 The "EX" and the "SOMA": How They Communicate 47

Part II Tumor Targeting

3 Polymeric Nanocarriers for Cancer Therapy 67

4 Targeted Liposomes and Micelles as Carriers for Cancer Therapy 95

5 Photodynamic Therapy for Cancer: Principles, Clinical Applications, and Nanotechnological Approaches 123

Part III Targeting the Immune System

6 Cancer Vaccines: Fundamentals and Strategies 163

7 Cancer Immune Modulation and Immunosuppressive Cells: Current and Future Therapeutic Approaches 187

8 Nanotechnology Approaches for Cancer Immunotherapy and Immunomodulation 215

Part IV Gene Therapy

9 RNAi-Based Nano-Oncologicals: Delivery and Clinical Applications 245

10 Nano-Platforms for Tumor-Targeted Delivery of Nucleic Acid Therapies 269

Part V Nanotheranostics

11 Multifunctional Gold Nanocarriers for Cancer Theranostics: From Bench to Bedside and Back Again? 295

12 Microbubbles as Theranostics Agents 329

13 Multimodal Nano-Systems for Cancer Diagnosis, Imaging, and Therapy 351

Part VI Translational Aspects of Nano-Oncologicals

14 Nanotoxicology: Towards Safety by Design 391

15 Regulatory Aspects of Oncologicals: Nanosystems Main Challenges 425

16 BO-110, a dsRNA-Based Anticancer Agent 453

Index 471

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