Special Issue "Nanotechnology and Cancer Therapeutics"

Guest Editor
Dr. Shaker A. Mousa
Pharmaceutical Research Institute at Albany College of Pharmacy and Health Sciences, 1 Discovery Drive (Room 238), Rensselaer, New York 12144, USA
E-Mail:
Phone: +1 518 694 7397
Fax: +1 518-694 7567
Interests: Drug discovery and drug development utilizing key enabling technologies including nanotechnology; biotechnology, stem cell, and novel pharmacotherapy; cell adhesion molecules and extracellular matrix; treatment and prevention of ischemic and coronary artery diseases; angiogenesis modulation; vascular and tissue remodeling; novel anti-platelet, anti-thrombotic and early detection and treatment of diseases with unmet medical need ranging from oncology, ophthalmology, cardiovascular, and vascular disorders

Dear Colleagues,

I would like to take this opportunity in inviting review articles having key innovations that would help accelerate progress in the field of Nanotechnology in early cancer detection and treatment. It is becoming clear to all of us that the application of nanotechnology and biotechnology utilizing nanoparticles for combined targeting and delivery of diagnostic and therapeutic agents has tremendous potential for early detection and treatment of various disorders. Nanoparticles may be constructed from a wide range of organic and inorganic materials such as emulsions, micelles, liposomes, dendrimers, quantum dots, and other polymeric materials. These materials are being used to encapsulate or covalently bind to the surface of the nanoparticles site directed moiety (s). Several multifunctional nanoparticles are being evaluated in early detection and therapeutics.

The next generation of nanoparticles-based research is directed at the consolidation of functions into strategically engineered multifunctional devices, which may ultimately facilitate the realization of individual therapy. These nanoparticles may be capable of (a) improving delivery of hydrophobic compounds (water insoluble); (b) improving stability of unstable peptides or easily inactivated compounds such as polyphenols and others; (c) identifying malignant cells via molecular detection; (c) visualizing their location in the body by providing enhanced contrast in medical imaging techniques; (d) targeting and killing diseased cells with minimal side effects through selective cell or tissue targeting; (e) polyvalent antidote for reversal of intoxication or toxins; and (f) delivering multiple drug targets for combination therapy.

One of the best known examples for reformulated, nanoparticles-based drug delivery is Doxil. Doxil, approved in the U.S. in 1995, is the poly (ethylene glycol)-coated, liposome-encapsulated form of doxorubicin in cancer chemotherapy. A more recent commercial product Abraxane, consists of an albumin-based reformulation of paclitaxel, which was approved in the U.S. in 2005. Other examples are in preclinical and early clinical investigations.

Dr. Shaker A. Mousa
Guest Editor

Submission

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• early detection using in vivo imaging modalities
• biosensor
• site directed delivery of chemotherapy into different tumor types using specific directed targets metal nanoparticles such as gold nanoparticles in the detection and treatment of breast cancer, and other types of cancer
• use of nanotechnology with nutraceuticals for chemoprevention

Type of Paper: Review
Title: Nanotechnology Based Early Detection and Targeted Therapy in Cancer: Nano-Bio Paradigms and Applications
Author: Shaker A. Mousa
Affiliation: The Pharmaceutical Research Institute at Albany, Albany College of Pharmacy and Health Sciences, One Discovery Drive, Rensselaer, New York 12144, NY, USA; E-Mail: Shaker.Mousa@acphs.edu
Abstract: Nanotechnology is a field which has been at the forefront of research over the past decades and its full potential has yet to be fully realized. One subset of nanotechnology that has emerged is nanomedicine, which has been able to exploit the unique properties of nano-sized particles for therapeutics. This review aims to discuss the current state of nanomedicine in the field of early detection of cancer and the subsequent targeted treatment. Current cancer detection methods rely on the patient to contact their provider when they feel ill or rely on non-specific screening methods, which unfortunately results in cancers being detected only after they have become too expensive for effective treatment. Furthermore, current treatment paradigms of cancer include mainly whole body treatment with chemotherapy agents exposing the patient to medications which non-specifically kill rapidly dividing cells, leading to debilitating whole body side effects. Nanomedicine has the potential to increase the specific treatment of cancer cells while leaving healthy cells intact through the use of novel nanoparticles to seek and treat cancer in the human body. Co-polymer poly(lactic-co-glycolic acid) (PLGA) nanotechnology has been approved by the FDA for the use of drug delivery, diagnostics and other applications including cardiovascular disease, cancer, vaccine and tissue engineering. However, there are undoubtedly toxicities of nanomedicines which have not yet been fully elucidated. This review discusses nanoparticles for the early detection and treatment of cancer such as: nanoshells, nanocantilevers, nanoprobes, nanocrystals, nanopolymers, nanocells, quantum dots, viruses and dendrimers. Known toxicities and possible mechanisms for toxicities of nanomedicines are also discussed.
Keywords: nanopharmaceuticals; nanomedicine; nanoparticles; dendrimer; PLGA, quantum dots; liposome; oncology; site directed delivery; early detection; therapy

Type of Paper: Review
Title: Virus-Based Nanotechnology for Cancer Therapeutics
Authors: Gopal Abbineni and Chuanbin Mao
Affiliation: Department of Chemistry & Biochemistry, University of Oklahoma, USA; E-Mail: cbmao@ou.edu (C.M.)
Abstract: Ever since the discovery of phage, commonly known as virus as an antibacterial agent in 1896 by prof. Hankin, research on viruses continues to receive great attention in this new era of nano-biotechnology. Viruses with its inherent nanosize architecture, genetic flexibility, stability to harsh conditions, circulatory behavior and targeting ability, in combination with nano science, are currently an excellent source for designing nano based therapeutics for cancer diagnosis and treatment. The current challenge in front of oncologists using viruses is to increase the therapeutic upload at the target site and selectively destroy the cancerous tissue with minimal adverse effects. In this review our focus is limited to engineered viruses including measles virus, herpes virus, pox viruses and filamentous viruses and their applications in oncology. At present some of these viruses represent a new class of therapeutic agents without any cross reactivity with current methods, thus can be used in combination with conventional treatment methods for effective cancer treatment.

Type of Paper: Article
Title: Nanoassembled Targeted Hybrid Magnetic Biocarriers for Combined Hyperthermic, Drug and Imaging Treatment: a Theranostic Approach to Cancer
Author: Giovanni Baldi
Affiliation: CE.RI.COL Research Center, Via Pietramarina, 129, 50059 Sovigliana, Vinci, Florence, Italy; E-Mail: baldig@colorobbia.it
Abstract: With over 10 million new cases per year world wide, cancer remains a difficult disease to treat and a significant cause of morbidity and mortality. In the last years there has been a variety of nanotechnology platform. Ideal nanomedicine platforms should be small in size (10–200 nm), provide high drug-loading densities, be efficient in targeting to the tumor tissues with minimal non specific uptake, provide responsive release mechanism to improve drug bioavailability and finally provide an imaging system to pre-validate and monitor therapy. The scientific community is seeking to exploit the intrinsic properties of magnetic nanoparticles (MNPs) to obtain medical breakthroughs in diagnosis and therapy. One of the main advantages of magnetic NPs is that they can be visualized acting as magnetic contrast agents (CA) for magnetic resonance imaging (MRI). Heated in a high-frequency magnetic field they trigger drug release or produce hyperthermia/ablation of tissues, currently reported as magnetic fluid hyperthermia (MFH). Accordingly, the term theranostic nanomedicine has been defined as an integrated nanotherapeutic system, which can diagnose, provide targeted therapy and monitor the response to therapy. In particular, oxide-based spinel ferrites are considered very promising for MRI and for hyperthermic treatment and iron oxides are good candidates thanks to their well-known biocompatibility. In this work, the development of an innovative system consisting of magnetite nanoparticles, showing high hyperthermic efficiency, embedded in PLGA-PEG polymeric matrix with the outer PEG surface functionalized with carboxylic group is reported. The binding with targeting units to the functionalized surface of nanobiocarriers (Anti hERG1 protein-human ether a gò gò related gene 1 and Epidermal Growth Factor (EGF)) is also reported to improve the targeting ability and the cellular uptake of the system. Paclitaxel and doxorubicin as drug model have been loaded during the nano engeneered assembly, the loading and drug loading efficiency has been evaluated as well as the release under EM field. In vitro hyperthermic experiments were performed on different cell cultures under electromagnetic field (100–200 KHz-20KA) and the cell viability has been detected as well. MRI test were also done, the magnetic core revealing a high transverse relaxivity acting as a negative contrast agent. According to preliminary in vitro toxicity, MRI and hyperthermic efficiency investigations the nanobiocarriers result greatly appealing to be simultaneously employed in both therapeutic and diagnostic applications. Development of a novel drug delivery device, being able to work in synergy with the hyperthermic effect under MRI monitoring, is the object of this scientific work.

Type of Paper: Review
Title: Phytochemicals Encapsulated in Nanoparticles in the Prevention and Treatment of Various Disorders: Special Emphasis on Cancer
Authors: Hasan Mukhtar, Imtiaz A. Siddiqui, Dhruba J. Bharali and Shaker A. Mousa
Affiliation: The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, 1 Discovery Drive, Rensselaer, NY, USA;
E-Mail: shaker.mousa@acphs.edu (S.A.M.)
Abstract: Several of the existing successful therapeutic drugs such as aspirin, warfarin, heparin, taxol, digoxin, and statins are derived from natural sources. Similarly, many successful health promoting substances such as green tea, resveratrol and curcumin are derived from plants. Despite the remarkable record of use of herbal medicine, natural extracts, supplements and other bioactive food components they often meet with skepticism as they exhibit only limited clinical success despite promising results in preclinical settings. Among many reasons considered responsible for the disappointment in human clinical trials, inefficient systemic delivery, limited bioavailability, and reduced half life are thought to play the major roles. Thus novel strategies are urgently required to achieve maximum benefit from phytochemicals by enhancing the bioavailability and improving efficacy via combinations of different effectively naturally-derived ingredients. Soy, red clover, pomegranate, green tea extracts, curcumin and others- derived products containing flavones and isoflavaones might have effective anti-oxidant and anti-inflammatory characteristics when used in combination.  We have recently demonstrated superior anti-angiogenesis and anti-cancer efficacy of chitosan and other compatible and bio-degradable nanoparticles encapsulating Green Tea Polyphenol Epigallocatechin-3-Gallate (ECGC) when compared to native EGCG in prostate cancer cell culture and xenograft models (Cancer Research. 2009, 69(5):1712-6). This review will highlight the potential of nanotechnology in improving the pharmacokinetic and pharmacodynamic profiles of phytochemicals for chemoprevention and treatment of various disorders including cancer.

Type of Paper: Review
Title: Two-Photon Fluorescence Imaging of Cancer Cells by Up-Converting Lanthanide Ion Doped Nanocrystals
Author: José García Solé
Affiliation: GIEL, Departamento de Física de Materiales, C-IV, Universidad Autónoma de Madrid, C/Francisco Tomás y Valiente 7, 28049 Madrid, Spain; E-Mail: jose.garcia_sole@uam.es
Abstract: During the last decade inorganic luminescent nanoparticles that emit visible light under near infrared (NIR) excitation are playing a relevant role for “in vitro” high resolution imaging of cancer cells by means of the novel multi-photon fluorescence microscopy. Indeed, semiconductor quantum dots (QDs) and metal nanoparticles, mostly gold nanorods (GNRs), are already commercially available for this purpose. In this work we review the role which is being played by a relatively new class of nanoparticles, based on lanthanide ion doped nanocrystals, to target and imaging cancer cells by means of two-photon fluorescence microscopy. These nanoparticles consist in fluoride nanocrystals co-activated with two different lanthanide ions; the excited donor ions (usually Yb3+) and the emitting acceptor ions (usually Er3+, Ho3+ or Tm3+), so that they can convert the NIR excitation radiation into emitted visible radiation by means of two-excitation-photons assisted energy transfer process. The higher conversion efficiency of these nanoparticles in respect to those of the QDs and GNRs, as well as the almost independence excitation/emission properties on the particle size, make them particularly promising for fluorescence imaging. We will show how these nanocrystals, when properly surface coated (functionalized), can be used to selective target of cancer cells. In addition these novel fluorescence nanocrystalline probes provide the possibility of intracellular imaging and thermometry of individual cancer cells.

Type of Paper: Review
Title: Multiple Targeting as a Clue for Nanoparticle-Based Cancer Therapy
Authors: Magali Gary-Bobo; Marie Maynadier, Ilaria Basile, Philippe Nirde and Marcel Garcia
Affiliations: UMR5247 CNRS, Universite Montpellier 1 et 2, 15 avenue Charles Flahault, 34000 Montpellier, France; E-Mail: marcel.garcia@inserm.fr (M.G.)
Abstract: Tumor targeting remains a major challenge in cancer therapy together with the early diagnosis and the therapeutic efficiency control. The emergence of nanotechnologies in medicine and the better knowledge of the tumoral environment (overexpressed biomarkers, microenvironment acidification, neovascularization) have encouraged the development of nanoparticles for medical applications. A variety of multifunctional nano-objects will be created in the near future as theranostics for a personalized and comprehensive cancer therapy. The review discusses the multiple targeting of nanoparticles based on tumoral and molecular characteristics, and on physical parameters. Tumor targeting of mesoporous nanoparticles could be improved by the enhanced penetrating retention effect due to tumor vasculature but also by covering their surface using tumor-selective ligands, such as oligosaccharides, peptides or antibodies. Moreover, these nanoparticules could take advantage of a spatio-temporal activation of their incorporated therapeutic agents triggered by methods such as light irradiation, magnetism or ultrasounds. These focal and non-invasive approaches are urgently expected in response to the ever-increasing number of small solid tumors detected from the cancer screening campaigns.
Keywords: tumor targeting, multifunctional nanoparticles, focal therapy, nanomedicine.