Begell House Inc.
Critical Reviews™ in Oncogenesis
CRO
0893-9675
19
3-4
2014
Preface: Nanotechnology in Imaging and Cancer Therapy
v-vii
10.1615/CritRevOncog.2014011726
Adriana
Haimovitz-Friedman
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, 1275 York Ave,
New York, NY 10065, USA
Dawn of Advanced Molecular Medicine: Nanotechnological Advancements in Cancer Imaging and Therapy
143-176
10.1615/CritRevOncog.2014011601
Charalambos
Kaittanis
Molecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Center, New York, NY
Travis M.
Shaffer
Molecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Center, New York, NY
Daniel L. J.
Thorek
Molecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Center, New York, NY
Jan
Grimm
Molecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Center, New York, NY
nanoparticles
oncology
drug delivery
chemotherapy
targeted therapeutics
Nanotechnology plays an increasingly important role not only in our everyday life (with all its benefits and dangers) but also in medicine. Nanoparticles are to date the most intriguing option to deliver high concentrations of agents specifically and directly to cancer cells; therefore, a wide variety of these nanomaterials has been developed and explored. These span the range from simple nanoagents to sophisticated smart devices for drug delivery or imaging. Nanomaterials usually provide a large surface area, allowing for decoration with a large amount of moieties on the surface for either additional functionalities or targeting. Besides using particles solely for imaging purposes, they can also carry as a payload a therapeutic agent. If both are combined within the same particle, a theranostic agent is created. The sophistication of highly developed nanotechnology targeting approaches provides a promising means for many clinical implementations and can provide improved applications for otherwise suboptimal formulations. In this review we will explore nanotechnology both for imaging and therapy to provide a general overview of the field and its impact on cancer imaging and therapy.
Liposome-Based Approaches for Delivery of Mainstream Chemotherapeutics: Preparation Methods, Liposome Designs, Therapeutic Efficacy
177-221
10.1615/CritRevOncog.2014011533
Michelle
Sempkowski
Department of Biomedical Engineering, Rutgers University, Piscataway, NJ
Trevan
Locke
Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ
Sally
Stras
Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ
Charles
Zhu
Department of Biomedical Engineering, Rutgers University, Piscataway, NJ
Stavroula
Sofou
Department of Biomedical Engineering, Rutgers University, Piscataway, NJ; Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ
liposomes
chemotherapy
liposomal chemotherapy
We review liposome-based delivery approaches that aim to address toxicities and to improve the therapeutic efficacy of mainstream chemotherapeutics, namely, doxorubicin, paclitaxel, and cisplatin. A brief review of the biomolecular mechanism(s) of action of these agents is followed by a description of characteristic examples of therapeutic approaches and of liposome membrane designs. Short reports on clinical studies are also included when applicable. The technical issues of different loading/encapsulation methods of these agents into liposomes are also discussed in terms of the physicochemical properties of both the agents themselves and of the lipid-based self-assemblies.
Nanoparticle Drug Formulations for Cancer Diagnosis and Treatment
223-245
10.1615/CritRevOncog.2014011563
Wilson
Poon
Department of Biomedical Engineering, McGill University, Montreal, Canada
Xuan
Zhang
Department of Biomedical Engineering, McGill University, Montreal, Canada
Jay
Nadeau
Department of Biomedical Engineering, McGill University, Montreal, Canada
nanoparticles
theranostics
quantum dots
gold
cancer
targeting
Over the past ten years, more than a billion dollars in U.S. government funding has been awarded to the development of nanomaterials for clinical diagnosis and therapy. In this article we will focus on one subset of nanotechnology: nanoparticle formulations of drugs intended to diagnose or treat cancer. Several nanoparticle drug preparations are now in widespread clinical use, and dozens are in the pipeline. In some cases the nanoparticles are simply passive drug carriers or contrast agents; in others, the nanoparticles have active therapeutic properties. Cancer, particularly solid tumors, is one of nanotechnology's key targets. The specific challenges involved in cancer treatment are those addressed by multifunctional materials, in particular, inaccessibility, widespread metastasis, low oxygen concentrations, and resistance to drugs and radiation. Nonetheless, major barriers still remain to effective nanoparticle design and approval.
Progress in Lipid-Based Nanoparticles for Cancer Therapy
247-260
10.1615/CritRevOncog.2014011815
Sarina
Grinberg
Department of Chemistry, Ben-Gurion University of the Negev, Israel
Charles
Linder
Zuckerberg Water Institute and Department of Biotechnology Engineering, Ben-Gurion University of the Negev, Israel
Eliahu
Heldman
Department of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev, Israel
nanoparticles
drug delivery
vesicles
liposomes
targeting
controlled drug release
Most conventional cancer therapeutics gain limited access to many types of tumors while having considerable adverse effects, resulting in low therapeutic efficacy and high toxicity. Therefore, research has now focused on the development of novel drug delivery systems (DDS) with the goal of maintaining high therapeutic drug levels at malignant cells and as low as possible drug levels in other cells. The introduction of nanotechnology has addressed some of these problems and opened up new avenues for improved cancer therapy. The design of nanoparticles for DDS takes into consideration issues such as targeting, controlled drug release and enhanced penetration via biological barriers. In this review we describe the design principles of targeted DDS for cancer therapy and the types of nanoparticles that are under development. Emphasis is put on lipid-based nanoparticles, particularly bolaamphiphilic vesicles that have tremendous potential in delivering therapeutic and diagnostic agents to specific cells following systemic administration.
Fibrillous Carbon Nanotube: An Unexpected Journey
261-268
10.1615/CritRevOncog.2014011442
Michael R.
McDevitt
Department of Radiology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065
David A.
Scheinberg
Department of Molecular Pharmacology and Chemistry, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065
carbon nanotube
fibrillar
pharmacokinetics
pharmacology
nanomaterial
The emergence of nanomedicine, a discipline at the nexus of materials engineering, chemistry, biology, and pharmacology, has generated much excitement in the field of translational medical research and provided some unexpected results. Nanomedicine seeks to introduce nanoscale technology to the practice of medicine via the design and development of nanomaterials possessing therapeutic or diagnostic functions. However, as expected, any modification of the base nanomaterial platform to decorate it with solublizing, targeting, therapeutic, or diagnostic modalities yields a material with a very different pharmacological profile than the original platform. Clearly, the goal of nanotechnology is to put into practice a novel synthetic substance in which the function of the complex is greater than the sum of its components. These new compositions must be thoroughly evaluated in vivo. Therefore, reliance on pharmacokinetic predictions based solely on the baseline profile of the original platform can confuse the field and delay progress. Carbon nanotube pharmacokinetic profiles provide an interesting example of this situation. Covalently functionalized nanotubes exhibit fibrillar pharmacology while those nanotubes that are not covalently functionalized transiently behave as fibers and then tend toward an overall colloidal profile in vivo.
Exploiting the Tumor Phenotype Using Biodegradable Submicron Carriers of Chemotherapeutic Drugs
269-280
10.1615/CritRevOncog.2014011518
Sean M.
Geary
Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, Iowa City, Iowa
Aliasger K.
Salem
Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, Iowa City, Iowa
submicron carriers
PLGA
liposomes
chemotherapy
tumor targeting
enhanced permeation and retention
effect
EPR
nanoparticles
Tumor tissues possess characteristics that distinguish them from healthy tissues and make them attractive targets for submicron carriers of chemotherapeutic drugs (CTX). CTX are generally administered systemically in free form to cancer patients resulting in unwanted cytotoxic effects and placing limitations on the deliverable CTX dose. In an effort to raise the therapeutic index of CTX there are now liposome-based CTX formulations in clinical use that are more tumor specific than the free form of CTX. However, progression to liposome-based chemotherapy in the clinic has been slow and there have been no approved formulations introduced in the last decade. Alternative carrier systems such as those made from the biodegradable polymer poly(lactic-co-glycolic) acid (PLGA) have been investigated in preclinical settings with promising outcomes. Here we review the principle behind biodegradable submicron carriers as CTX delivery vehicles for solid tumors with a specific focUS on liposomes and PLGA-based carriers, highlighting the strengths and weaknesses of each system
Development of Nanoscale Approaches for Ovarian Cancer Therapeutics and Diagnostics
281-315
10.1615/CritRevOncog.2014011455
Sarah A.
Engelberth
SUNY College of Nanoscale Science and Engineering, Albany NY 12203
Nadine
Hempel
SUNY College of Nanoscale Science and Engineering, Albany NY 12203
Magnus
Bergkvist
SUNY College of Nanoscale Science and Engineering, Albany NY 12203
clinical trials
photodynamic therapy
gene therapy
Ovarian cancer is the deadliest of all gynecological cancers and the fifth leading cause of death due to cancer in women. This is largely due to late-stage diagnosis, poor prognosis related to advanced-stage disease, and the high recurrence rate associated with development of chemoresistance. Survival statistics have not improved significantly over the last three decades, highlighting the fact that improved therapeutic strategies and early detection require substantial improvements. Here, we review and highlight nanotechnology-based approaches that seek to address this need. The success of Doxil, a PEGylated liposomal nanoencapsulation of doxorubicin, which was approved by the FDA for use on recurrent ovarian cancer, has paved the way for the current wave of nanoparticle formulations in drug discovery and clinical trials. We discuss and summarize new nanoformulations that are currently moving into clinical trials and highlight novel nanotherapeutic strategies that have shown promising results in preclinical in vivo studies. Further, the potential for nanomaterials in diagnostic imaging techniques and the ability to leverage nanotechnology for early detection of ovarian cancer are also discussed.