Pharmacokinetics and pharmacodynamics of lipidic nano-particles in ...

Below, you will find a survey of recent articles related to
the field of NanoBioTechnology for Cancer.

Source: Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal
Chemistry - Anti-Cancer Agents), Volume 6, Number 6, November 2006, pp. 513-523(11)
Publisher: Bentham Science Publishers
Pharmacokinetics and pharmacodynamics of lipidic nano-particles in cancer.
• Allen TM,
• Cheng WW,
• Hare JI,
• Laginha KM.
Department of Pharmacology, University of Alberta, Edmonton, AB, Canada.
terry.allen@ualberta.ca
Nanoscale drug delivery systems (DDS) are used to circumvent some of the non-
ideal properties of conventional anticancer chemotherapy drugs. Manipulation of the
physical properties of DDS provides improved control over the pharmacokinetics (PK)
and pharmacodynamics (PD) of the encapsulated drugs relative to free drugs.
Liposomes are the archetypical nanoscale DDS and the first of these received clinical
approval in 1990. DOXIL, liposomal doxorubicin, was the first commercially available
liposomal anticancer drug (1995). It has an enhanced circulation half-life compared
to the free drug because of its surface-grafted polyethylene glycol coating. DOXIL
passively targets solid tumors, and once the liposomes localize in the tumor
interstitial space, the cytotoxic drug is slowly released within the tumor. Liposomes
can act as sustained release delivery system and manipulation of properties such as,
liposome diameter, drug release rate, bioavailability and dosing schedule can
significantly impact the therapeutic outcome of the liposomal drugs. This review will
focus on how alteration of these properties can impact the therapeutic efficacy and
side effect profiles of DDS.

1: Oncol Rep. 2005 Jun;13(6):1003-7. Links
Nanotechnology blooms, at last (Review).
• Gordon EM,
• Hall FL.
Department of Pediatrics, Children's Hospital of Los Angeles, University of Southern California
Keck School of Medicine, Los Angeles, CA 910027, USA. emgordon@epeiusbiotech.com
Clinical trials for deadly pancreatic cancer have recently opened on two continents to
evaluate the safety and efficacy of engineered nanoparticles guided by a targeted
delivery system (TDS) to overcome the daunting barriers of turbulence, dilution,

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filtration, and inactivation encountered in the human circulatory system to deliver a
killing designer gene to metastatic tumors that are refractory to conventional
chemotherapy. The first patients receiving multiple intravenous infusions of the TDS-
encapsulated genetic bullets have all responded favorably, prompting the FDA to
grant orphan drug status for the nanobiotic medicine, Rexin-G, to assist in the
development of this new cancer treatment. This review/commentary is an effort to
translate the arcane terminology of physiology, biochemistry, and molecular genetics
into the more generally accessible language of nanotechnology and medical delivery.
While the text is somewhat erudite and laden at times with inconspicuous literary
allusions, descriptions of the elegant bioengineering of nano-scale gene delivery
vehicles are clear and the numerous references to classical mechanics of the
Industrial Age are helpful.
PMID: 15870914 [PubMed - indexed for MEDLINE]
1: Technol Cancer Res Treat. 2005 Aug;4(4):407-16.
Links
Nanotechnology-based drug delivery for cancer.
• Jain KK.
Jain PharmaBiotech, Blaesiring 7, CH-4057 Basel, Switzerland. jain@pharmabiotech.ch
Nanobiotechnologies have been applied to improve drug delivery and to overcome
some of the problems of drug delivery in cancer. These can be classified into many
categories that include use of various nanoparticles, nanoencapsulation, targeted
delivery to tumors of various organs, and combination with other methods of
treatment of cancer such as radiotherapy. Nanoparticles are also used for gene
therapy for cancer. Some of the technologies enable combination of diagnostics with
therapeutics which will be important for the personalized management of cancer.
Some of the limitations of these technologies and prospects for future development
are discussed.
PMID: 16029059 [PubMed - indexed for MEDLINE]


1: Adv Drug Deliv Rev. 2004 Sep 22;56(11):1649-59.
Links
Nanoparticle and targeted systems for cancer therapy.
• Brannon-Peppas L,
• Blanchette JO.
Department of Biomedical Engineering, The University of Texas at Austin, 1 University Station,
C0800, Austin, TX 78712-0231, USA. peppas@mail.utexas.edu

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This review explores recent work directed towards more targeted treatment of
cancer, whether through more specific anti-cancer agents or through methods of
delivery. These areas include delivery by avoiding the reticuloendothelial system,
utilizing the enhanced permeability and retention effect and tumor-specific targeting.
Treatment opportunities using antibody-targeted therapies are summarized. The
ability to treat cancer by targeting delivery through angiogenesis is also discussed
and antiangiogenic drugs in clinical trials are presented. Delivery methods that
specifically use nanoparticles are also highlighted, including both degradable and
nondegradable polymers.
PMID: 15350294 [PubMed - indexed for MEDLINE]


Review Article
Emerging implications of nanotechnology on cancer diagnostics and therapeutics
Alex G. Cuenca, MD 1, Huabei Jiang, PhD 2, Steven N. Hochwald, MD 1, Matthew Delano, MD 1, William G. Cance, MD 1,
Stephen R. Grobmyer, MD 1 *
1Division of Surgical Oncology, Department of Surgery, University of Florida, Gainesville, Florida
2Department of Biomedical Engineering, University of Florida, Gainesville, Florida
email: Stephen R. Grobmyer (stephen.grobmyer@surgery.ufl.edu)
*Correspondence to Stephen R. Grobmyer, Division of Surgical Oncology, Department of Surgery, University of
Florida, 1600 SW Archer Road, P.O. Box 100286, Gainesville, FL 32610
Fax: (352) 265-0262

KEYWORDS
nanotechnology • review • cancer • quantum dots • nanoshells • gold nanoparticles • paramagnetic nanoparticles • carbon
nanotubes • photothermal ablation • liposomes
ABSTRACT
Nanotechnology is multidisciplinary field that involves the design and engineering of objects <500 nanometers (nm) in size.
The National Cancer Institute has recognized that nanotechnology offers an extraordinary, paradigm-changing opportunity to
make significant advances in cancer diagnosis and treatment. In the last several decades, nanotechnology has been studied
and developed primarily for use in novel drug-delivery systems (e.g. liposomes, gelatin nanoparticles, micelles). A recent
explosion in engineering and technology has led to 1) the development of many new nanoscale platforms, including quantum
dots, nanoshells, gold nanoparticles, paramagnetic nanoparticles, and carbon nanotubes, and 2) improvements in traditional,
lipid-based nanoscale platforms. The emerging implications of these platforms for advances in cancer diagnostics and
therapeutics form the basis of this review. A widespread understanding of these new technologies is important, because they
currently are being integrated into the clinical practice of oncology. Cancer 2006. © 2006 American Cancer Society.

Received: 3 February 2006; Revised: 28 March 2006; Accepted: 3 April 2006


1: Neurosurgery. 2006 Jun;58(6):1009-26; discussion 1009-26.
Links
Toward the emergence of nanoneurosurgery: part III--nanomedicine: targeted
nanotherapy, nanosurgery, and progress toward the realization of nanoneurosurgery.
• Leary SP,
• Liu CY,
• Apuzzo ML.

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Department of Neurological Surgery, Keck School of Medicine, University of Southern
California, Los Angeles, California, USA.
The notion of nanotechnology has evolved since its inception as a fantastic
conceptual idea to its current position as a mainstream research initiative with broad
applications among all divisions of science. In the first part of this series, we
reviewed the structures and principles that comprise the main body of knowledge of
nanoscience and nanotechnology. In the second part, we discussed applications of
nanotechnology to the emerging field of nanomedicine, with specific attention on
medical diagnostics and imaging. This article further explores the applications of
nanotechnology to nanomedicine. Specific attention is given to developments in
therapeutic modalities, including advanced drug delivery systems and targeted
nanotherapy, which will form the basis for the treatment arm of mature
nanomedicine. A variety of modalities are discussed, including polymeric
nanoparticles, micelles, liposomes, dendrimers, fullerenes, hydrogels, nanoshells,
and smart surfaces. Applications of nanotechnology to nanosurgery and
nanoneurosurgery are presented. Femtosecond laser systems, nanoneedles, and
nanotweezers are presented as technologies that are operational at the nanoscale
level and have the potential to revolutionize the practice of neurosurgery in a
profound and momentous way.
PMID: 16723880 [PubMed - indexed for MEDLINE]

1: Expert Rev Mol Diagn. 2006 May;6(3):307-18.
Links
Nanotechnology for cancer diagnostics: promises and challenges.
• Grodzinski P,
• Silver M,
• Molnar LK.
National Cancer Institute, 31 Center Drive, MSC 2580 Room 10A52, Bethesda, MD 20892, USA.
grodzinp@mail.nih.gov
Despite recent progress in the treatment of cancer, the majority of cases are still
diagnosed only after tumors have metastasized, leaving the patient with a grim
prognosis. However, there may be an opportunity to drastically reduce the burden of
cancer, if the disease can be detected early enough. Nanotechnology is in a unique
position to transform cancer diagnostics and to produce a new generation of
biosensors and medical imaging techniques with higher sensitivity and precision of
recognition. This review examines the in vitro and in vivo diagnostic applications of
nanoparticles, and other nanodevices that are likely to have an impact on the field in
the future. Future developments that may lead to the realization of multifunctional
detection and treatment nanoparticle platforms are also discussed.

1: Technol Cancer Res Treat. 2005 Dec;4(6):645-50.
Links

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Role of nanobiotechnology in developing personalized medicine for cancer.
• Jain KK.
Jain PharmaBiotech, Blaesiring, Basel, Switzerland. jain@pharmabiotech.ch
Personalized medicine simply means the prescription of specific therapeutics best
suited for an individual. Personalization of cancer therapies is based on a better
understanding of the disease at the molecular level. Nanotechnology will play an
important role in this area. Nanobiotechnology is being used to refine discovery of
biomarkers, molecular diagnostics, drug discovery and drug delivery, which are
important basic components of personalized medicine and are applicable to
management of cancer as well. Examples are given of the application of quantum
dots, gold nanoparticles, and molecular imaging in diagnostics and combination with
therapeutics -- another important feature of personalized medicine. Personalized
medicine is beginning to be recognized and is expected to become a part of medical
practice within the next decade. Personalized management of cancer, facilitated by
nanobiotechnology, is expected to enable early detection of cancer, more effective
and less toxic treatment increasing the chances of cure.
PMID: 16292884 [PubMed - indexed for MEDLINE]
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J Photochem Photobiol B. 2005 Nov 1;81(2):67-75. Epub 2005 Aug 19. Links
Electroporation of transplantable tumour for the enhanced accumulation of
photosensitizers.Tamosiunas M, Bagdonas S, Didziapetriene J, Rotomskis R.
Vilnius University, Laser Research Center, 10222 Vilnius, Lithuania.

The aim of this study was to verify whether electroporation could increase the accumulation of the
hydrophilic photosensitizers: aluminium phthalocyanine tetrasulphonate (AlPcS(4)) and chlorin e(6) (C
e(6)) in tumour tissue. The experiment was performed in vivo using hybrid mice (C57Bl/CBA) bearing
hepatoma A22 (MH-A22) tumours transplanted in the right haunch. The time dependence of the
fluorescence intensity of administered photosensitizers was measured after the ordinary and
electrically stimulated delivery. The obtained fluorescence spectroscopy results implied the tumour
being affected by an electrical field in a way, which led to a higher accumulation of both
photosensitizers (AlPcS(4) and C e(6)) in the periphery of the tumour and it superficial layer. Our pilot
study suggests that electroporation could be considered as a useful procedure seeking for the more
effective application of photodynamic tumour treatment.

1: Medicina (Kaunas). 2006;42(7):542-58. Links
[Nanoparticles in diagnostics and therapy: towards nanomedicine][Article in Lithuanian]
Rotomskis R, Streckyte G, Karabanovas V.
Laser Research Center, Vilnius University, Vilnius, Lithuania. ricardas.rotomskis@ff.vu.lt

Nanotechnology is an area of scientific research and technology development dealing with the
structures and devices with length scales in the 1- to 100-nanometer range. Multifunctional
nanoparticles that can target, diagnose, and treat diseases such as cancer are designed and
developed. Numerous studies have shown that anticancer drugs encapsulated into nanoparticles can
be delivered to target tumor cells and tissue. This would increase antitumor efficacy and reduce
systemic side effects. Quantum dots are kind of nanoparticles with unique photochemical and
photophysical properties. They are several orders of magnitude brighter than conventional
fluorophores, and their emission spectra are very narrow and can be tuned by adjusting the size of the
dots. Quantum dots are a new class of fluorescent labels with improved brightness and resistance
against photobleaching. These properties could improve the sensitivity of biological detection and
imaging by at least 10- to 100-fold. In this review, data of tumor targeting with conventional and long-

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circulating nanoparticles as well as applications of semiconductor quantum dots for in vivo imaging are
discussed.
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Cancer Invest. 2005;23(1):36-46.
Pathology of the future: molecular profiling for targeted therapy.
• Espina V,
• Geho D,
• Mehta AI,
• Petricoin EF 3rd,
• Liotta LA,
• Rosenblatt KP.
National Cancer Institute, Laboratory of Pathology, Bethesda, Maryland, USA.
Recent evidence suggests that each patient's cancer has a unique subset of molecular pathogenetic
derangements. These derangements may both genetic and proteomic alterations. Genomic and
proteomic research tools enable genome-wide assessment of gene expression as well as kinase driven
cell signaling events. These tools are illuminating the molecular derangements of individual tumors,
even if these tumors have similar morphological characteristics. A combination of laser capture
microdissection with multiplexed phosphoproteomic analysis using reverse phase protein microarray
technology is being used to identify protein molecular signatures of individual tumors. The in vivo
state of multiple kinase driven signal pathways may be evaluated by reverse phase protein microarray
with a panel of specific antibodies developed based upon our knowledge of biological processes.
Molecular profiling of individual patient's tumors is currently being evaluated in clinical trials at the
National Institutes of Health, National Cancer Institute for monitoring Epidermal Growth Factor (EGF)
cell signaling events for patients with breast and ovarian cancer.

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