Special Issue "Nanotechnology and Cancer Therapeutics"

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A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (30 November 2010)

Special Issue Editor

Guest Editor
Prof. Dr. Shaker A. Mousa

The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, 1 Discovery Drive (Room 238), Rensselaer, NY 12144, USA
Website | E-Mail
Phone: +518-694-7397
Fax: +1 518-694 7567
Interests: pharmaceuticals, biopharmaceuticals, and diagnostics; nanomedicine; cardiovascular diseases; neurological disorders; hematology and oncology; biosimilar and nanosimilar; angiogenesis, inflammation, thrombosis, integrin and cell adhesion molecules; target identification, molecular mechanisms and signaling pathways; preclinical, clinical, marketing and post marketing studies; regulatory and ethical issues

Special Issue Information

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

Keywords

  • 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

Published Papers (10 papers)

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Research

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Open AccessArticle Plasmonic Nanobubbles as Tunable Cellular Probes for Cancer Theranostics
Cancers 2011, 3(1), 802-840; doi:10.3390/cancers3010802
Received: 19 January 2011 / Revised: 12 February 2011 / Accepted: 17 February 2011 / Published: 23 February 2011
Cited by 28 | PDF Full-text (1984 KB) | HTML Full-text | XML Full-text
Abstract
This review is focused on a novel cellular probe, the plasmonic nanobubble (PNB), which has the dynamically tunable and multiple functions of imaging, diagnosis, delivery, therapy and, ultimately, theranostics. The concept of theranostics was recently introduced in order to unite the clinically important
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This review is focused on a novel cellular probe, the plasmonic nanobubble (PNB), which has the dynamically tunable and multiple functions of imaging, diagnosis, delivery, therapy and, ultimately, theranostics. The concept of theranostics was recently introduced in order to unite the clinically important stages of treatment, namely diagnosis, therapy and therapy guidance, into one single, rapid and highly accurate procedure. Cell level theranostics will have far-reaching implications for the treatment of cancer and other diseases at their earliest stages. PNBs were developed to support cell level theranostics as a new generation of on-demand tunable cellular probes. A PNB is a transient vapor nanobubble that is generated within nanoseconds around an overheated plasmonic nanoparticle with a short laser pulse. In the short term, we expect that PNB technology will be rapidly adaptable to clinical medicine, where the single cell resolution it provides will be critical for diagnosing incipient or residual disease and eliminating cancer cells, while leaving healthy cells intact. This review discusses mechanisms of plasmonic nanobubbles and their biomedical applications with the focus on cancer cell theranostics. Full article
(This article belongs to the Special Issue Nanotechnology and Cancer Therapeutics)
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Open AccessArticle Anti-Neuroblastoma Activity of Gold Nanorods Bound with GD2 Monoclonal Antibody under Near-Infrared Laser Irradiation
Cancers 2011, 3(1), 227-240; doi:10.3390/cancers3010227
Received: 7 December 2010 / Revised: 26 December 2010 / Accepted: 4 January 2011 / Published: 6 January 2011
Cited by 9 | PDF Full-text (539 KB) | HTML Full-text | XML Full-text
Abstract
High-risk neuroblastoma is one of the most common deaths in pediatric oncology. Current treatment of this disease involves a coordinated sequence of chemotherapy, surgery, and radiation. Further advances in therapy will require the targeting of tumor cells in a more selective and efficient
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High-risk neuroblastoma is one of the most common deaths in pediatric oncology. Current treatment of this disease involves a coordinated sequence of chemotherapy, surgery, and radiation. Further advances in therapy will require the targeting of tumor cells in a more selective and efficient way so that survival can be improved without substantially increasing toxicity. To achieve tumor-selective delivery, disialoganglioside (GD2) expressed by almost all neuroblastoma tumors represents a potential molecular target that can be exploited for tumor-selective delivery. In this study, GD2 monoclonal antibody (anti-GD2) was conjugated to gold nanorods (GNRs) which are one of anisotropic nanomaterials that can absorb near-infrared (NIR) laser light and convert it to energy for photothermolysis of tumor cells. Thiolated chitosan, due to its biocompatibility, was used to replace cetyltrimethylammonium bromide (CTAB) originally used in the synthesis of gold nanorods. In order to specifically target GD2 overexpressed on the surface of neuroblastoma stNB-V1 cells, anti-GD2 was conjugated to chitosan modified GNRs (CGNRs). To examine the fate of CGNRs conjugated with anti-GD2 after incubation with neuroblastoma cells, rhadoamine B was labeled on CGNRs functionalized with anti-GD2. Our results illustrated that anti-GD2-conjugated CGNRs were extensively endocytosed by GD2+ stNB-V1 neuroblastoma cells via antibody-mediated endocytosis. In addition, we showed that anti-GD2 bound CGNRs were not internalized by GD2 SH-SY5Y neuroblastoma cells. After anti-GD2-linked CGNRs were incubated with neuroblatoma cells for six hours, the treated cells were further irradiated with 808 nm NIR laser. Post-NIR laser exposure, when examined by calcein-AM dye, stNB-V1 cells all underwent necrosis, while non-GD2 expressing SH-SY5Y cells all remained viable. Based on the in vitro study, CGNRs bound with anti-GD2 has the potential to be utilized as a therapeutic thermal coupling agent that generates heat sufficient to selectively kill neuroblastoma cells under NIR laser light exposure. Full article
(This article belongs to the Special Issue Nanotechnology and Cancer Therapeutics)
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Open AccessArticle Doxorubicin-Loaded PEG-PCL-PEG Micelle Using Xenograft Model of Nude Mice: Effect of Multiple Administration of Micelle on the Suppression of Human Breast Cancer
Cancers 2011, 3(1), 61-78; doi:10.3390/cancers3010061
Received: 11 November 2010 / Revised: 20 December 2010 / Accepted: 27 December 2010 / Published: 28 December 2010
Cited by 22 | PDF Full-text (1187 KB) | HTML Full-text | XML Full-text
Abstract
The triblock copolymer is composed of two identical hydrophilic segments: Monomethoxy poly(ethylene glycol) (mPEG) and one hydrophobic segment poly(ε‑caprolactone) (PCL); which is synthesized by coupling of mPEG-PCL-OH and mPEG‑COOH in a mild condition using dicyclohexylcarbodiimide and 4-dimethylamino pyridine. The amphiphilic block copolymer can
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The triblock copolymer is composed of two identical hydrophilic segments: Monomethoxy poly(ethylene glycol) (mPEG) and one hydrophobic segment poly(ε‑caprolactone) (PCL); which is synthesized by coupling of mPEG-PCL-OH and mPEG‑COOH in a mild condition using dicyclohexylcarbodiimide and 4-dimethylamino pyridine. The amphiphilic block copolymer can self-assemble into nanoscopic micelles to accommodate doxorubixin (DOX) in the hydrophobic core. The physicochemical properties and in vitro tests, including cytotoxicity of the micelles, have been characterized in our previous study. In this study, DOX was encapsulated into micelles with a drug loading content of 8.5%. Confocal microscopy indicated that DOX was internalized into the cytoplasm via endocystosis. A dose-finding scheme of the polymeric micelle (placebo) showed a safe dose of PEG-PCL-PEG micelles was 71.4 mg/kg in mice. Importantly, the circulation time of DOX-loaded micelles in the plasma significantly increased compared to that of free DOX in rats. A biodistribution study displayed that plasma extravasation of DOX in liver and spleen occurred in the first four hours. Lastly, the tumor growth of human breast cancer cells in nude mice was suppressed by multiple injections (5 mg/kg, three times daily on day 0, 7 and 14) of DOX-loaded micelles as compared to multiple administrations of free DOX. Full article
(This article belongs to the Special Issue Nanotechnology and Cancer Therapeutics)
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Review

Jump to: Research

Open AccessReview High Resolution Fluorescence Imaging of Cancers Using Lanthanide Ion-Doped Upconverting Nanocrystals
Cancers 2012, 4(4), 1067-1105; doi:10.3390/cancers4041067
Received: 13 August 2012 / Revised: 20 September 2012 / Accepted: 15 October 2012 / Published: 22 October 2012
Cited by 24 | PDF Full-text (2057 KB) | HTML Full-text | XML Full-text
Abstract
During the last decade inorganic luminescent nanoparticles that emit visible light under near infrared (NIR) excitation (in the biological window) have played a relevant role for high resolution imaging of cancer. Indeed, semiconductor quantum dots (QDs) and metal nanoparticles, mostly gold nanorods (GNRs),
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During the last decade inorganic luminescent nanoparticles that emit visible light under near infrared (NIR) excitation (in the biological window) have played a relevant role for high resolution imaging of cancer. 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 image cancer cells using upconversion fluorescence microscopy. These nanoparticles are insulating nanocrystals that are usually doped with small percentages of two different rare earth (lanthanide) ions: The excited donor ions (usually Yb3+ ion) that absorb the NIR excitation and the acceptor ions (usually Er3+, Ho3+ or Tm3+), that are responsible for the emitted visible (or also near infrared) radiation. The higher conversion efficiency of these nanoparticles in respect to those based on QDs and GNRs, as well as the almost independent excitation/emission properties from the particle size, make them particularly promising for fluorescence imaging. The different approaches of these novel nanoparticles devoted to "in vitro" and "in vivo" cancer imaging, selective targeting and treatment are examined in this review. Full article
(This article belongs to the Special Issue Nanotechnology and Cancer Therapeutics)
Open AccessReview Assessment of the Evolution of Cancer Treatment Therapies
Cancers 2011, 3(3), 3279-3330; doi:10.3390/cancers3033279
Received: 16 June 2011 / Revised: 7 July 2011 / Accepted: 8 August 2011 / Published: 12 August 2011
Cited by 5 | PDF Full-text (889 KB) | HTML Full-text | XML Full-text
Abstract
Cancer therapy has been characterized throughout history by ups and downs, not only due to the ineffectiveness of treatments and side effects, but also by hope and the reality of complete remission and cure in many cases. Within the therapeutic arsenal, alongside surgery
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Cancer therapy has been characterized throughout history by ups and downs, not only due to the ineffectiveness of treatments and side effects, but also by hope and the reality of complete remission and cure in many cases. Within the therapeutic arsenal, alongside surgery in the case of solid tumors, are the antitumor drugs and radiation that have been the treatment of choice in some instances. In recent years, immunotherapy has become an important therapeutic alternative, and is now the first choice in many cases. Nanotechnology has recently arrived on the scene, offering nanostructures as new therapeutic alternatives for controlled drug delivery, for combining imaging and treatment, applying hyperthermia, and providing directed target therapy, among others. These therapies can be applied either alone or in combination with other components (antibodies, peptides, folic acid, etc.). In addition, gene therapy is also offering promising new methods for treatment. Here, we present a review of the evolution of cancer treatments, starting with chemotherapy, surgery, radiation and immunotherapy, and moving on to the most promising cutting-edge therapies (gene therapy and nanomedicine). We offer an historical point of view that covers the arrival of these therapies to clinical practice and the market, and the promises and challenges they present. Full article
(This article belongs to the Special Issue Nanotechnology and Cancer Therapeutics)
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Open AccessReview Gold Nanostructures as a Platform for Combinational Therapy in Future Cancer Therapeutics
Cancers 2011, 3(1), 1081-1110; doi:10.3390/cancers3011081
Received: 17 December 2010 / Revised: 19 January 2011 / Accepted: 21 January 2011 / Published: 4 March 2011
Cited by 67 | PDF Full-text (1890 KB) | HTML Full-text | XML Full-text
Abstract
The field of nanotechnology is currently undergoing explosive development on many fronts. The technology is expected to generate innovations and play a critical role in cancer therapeutics. Among other nanoparticle (NP) systems, there has been tremendous progress made in the use of spherical
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The field of nanotechnology is currently undergoing explosive development on many fronts. The technology is expected to generate innovations and play a critical role in cancer therapeutics. Among other nanoparticle (NP) systems, there has been tremendous progress made in the use of spherical gold NPs (GNPs), gold nanorods (GNRs), gold nanoshells (GNSs) and gold nanocages (GNCs) in cancer therapeutics. In treating cancer, radiation therapy and chemotherapy remain the most widely used treatment options and recent developments in cancer research show that the incorporation of gold nanostructures into these protocols has enhanced tumor cell killing. These nanostructures further provide strategies for better loading, targeting, and controlling the release of drugs to minimize the side effects of highly toxic anticancer drugs used in chemotherapy and photodynamic therapy. In addition, the heat generation capability of gold nanostructures upon exposure to UV or near infrared light is being used to damage tumor cells locally in photothermal therapy. Hence, gold nanostructures provide a versatile platform to integrate many therapeutic options leading to effective combinational therapy in the fight against cancer. In this review article, the recent progress in the development of gold-based NPs towards improved therapeutics will be discussed. A multifunctional platform based on gold nanostructures with targeting ligands, therapeutic molecules, and imaging contrast agents, holds an array of promising directions for cancer research. Full article
(This article belongs to the Special Issue Nanotechnology and Cancer Therapeutics)
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Open AccessReview Progress in Nanotechnology Based Approaches to Enhance the Potential of Chemopreventive Agents
Cancers 2011, 3(1), 428-445; doi:10.3390/cancers3010428
Received: 14 December 2010 / Revised: 4 January 2011 / Accepted: 12 January 2011 / Published: 21 January 2011
Cited by 22 | PDF Full-text (291 KB) | HTML Full-text | XML Full-text
Abstract
Cancer chemoprevention is defined as the use of natural agents to suppress, reverse or prevent the carcinogenic process from turning into aggressive cancer. Over the last two decades, multiple natural dietary compounds with diverse chemical structures such flavonoids, tannins, curcumins and polyphenols have
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Cancer chemoprevention is defined as the use of natural agents to suppress, reverse or prevent the carcinogenic process from turning into aggressive cancer. Over the last two decades, multiple natural dietary compounds with diverse chemical structures such flavonoids, tannins, curcumins and polyphenols have been proposed as chemopreventive agents. These agents have proven excellent anticancer potential in the laboratory setting, however, the observed effects in vitro do not translate in clinic where they fail to live up to their expectations. Among the various reasons for this discrepancy include inefficient systemic delivery and robust bioavailability. To overcome this barrier, researchers have focused towards coupling these agents with nano based encapsulation technology that in principle will enhance bioavailability and ultimately benefit clinical outcome. The last decade has witnessed rapid advancement in the development of nanochemopreventive technology with emergence of many nano encapsulated formulations of different dietary anticancer agents. This review summarizes the most up-to-date knowledge on the studies performed in nanochemoprevention, their proposed use in the clinic and future directions in which this field is heading. As the knowledge of the dynamics of nano encapsulation evolves, it is expected that researchers will bring forward newer and far more superior nanochemopreventive agents that may become standard drugs for different cancers. Full article
(This article belongs to the Special Issue Nanotechnology and Cancer Therapeutics)
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Open AccessReview Clinically Relevant Anticancer Polymer Paclitaxel Therapeutics
Cancers 2011, 3(1), 17-42; doi:10.3390/cancers3010017
Received: 12 November 2010 / Revised: 10 December 2010 / Accepted: 22 December 2010 / Published: 23 December 2010
Cited by 14 | PDF Full-text (692 KB) | HTML Full-text | XML Full-text
Abstract
The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release
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The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release of active drugs. Each polymer exhibits its own intrinsic issues providing the advantage of flexibility. However, none have as yet been approved by the U.S. Food and Drug Administration. General aspects of polymer and nano-particle therapeutics have been reviewed. Here we focus this review on specific clinically relevant anticancer polymer paclitaxel therapeutics. We emphasize their chemistry and formulation, in vitro activity on some human cancer cell lines, plasma pharmacokinetics and tumor accumulation, in vivo efficacy, and clinical outcomes. Furthermore, we include a short review of our recent developments of a novel poly(L-g-glutamylglutamine)-paclitaxel nano-conjugate (PGG-PTX). PGG-PTX has its own unique property of forming nano-particles. It has also been shown to possess a favorable profile of pharmacokinetics and to exhibit efficacious potency. This review might shed light on designing new and better polymer paclitaxel therapeutics for potential anticancer applications in the clinic. Full article
(This article belongs to the Special Issue Nanotechnology and Cancer Therapeutics)
Open AccessReview A Comparative Study of Two Folate-Conjugated Gold Nanoparticles for Cancer Nanotechnology Applications
Cancers 2010, 2(4), 1911-1928; doi:10.3390/cancers2041911
Received: 29 October 2010 / Revised: 10 November 2010 / Accepted: 11 November 2010 / Published: 18 November 2010
Cited by 41 | PDF Full-text (815 KB) | HTML Full-text | XML Full-text
Abstract
We report a comparative study of synthesis, characteristics and in vitro tests of two folate-conjugated gold nanoparticles (AuNP) differing in linkers and AuNP sizes for selective targeting of folate-receptor positive cancerous cells. The linkers chosen were 4-aminothiophenol (4Atp) and 6-mercapto-1-hexanol (
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We report a comparative study of synthesis, characteristics and in vitro tests of two folate-conjugated gold nanoparticles (AuNP) differing in linkers and AuNP sizes for selective targeting of folate-receptor positive cancerous cells. The linkers chosen were 4-aminothiophenol (4Atp) and 6-mercapto-1-hexanol (MH) with nanoconjugate products named Folate-4Atp-AuNP and Folate-MH-AuNP. We report the folate-receptor tissue distribution and its endocytosis for targeted nanotechnology. Comparison of the two nanoconjugates’ syntheses and characterization is also reported, including materials and methods of synthesis, UV-visible absorption spectroscopic measurements, Fourier Transform Infra Red (FTIR) measurements, Transmission electron microscopy (TEM) images and size distributions, X-ray diffraction data, elemental analyses and chemical stability comparison. In addition to the analytical characterization of the nanoconjugates, the cell lethality was measured in HeLa (high level of folate receptor expression) and MCF-7 (low level of folate receptor expression) cells. The nanoconjugates themselves, as well as the intense pulsed light (IPL) were not harmful to cell viability. However, upon stimulation of the folate targeted nanoconjugates with the IPL, ~98% cell killing was found in HeLa cells and only ~9% in MCF-7 cells after four hours incubation with the nanoconjugate. This demonstrates that folate targeting is effective in selecting for specific cell populations. Considering the various comparisons made, we conclude that Folate-4Atp-AuNP is superior to Folate-MH-AuNP for cancer therapy. Full article
(This article belongs to the Special Issue Nanotechnology and Cancer Therapeutics)
Open AccessReview Nanoparticles in Sentinel Lymph Node Assessment in Breast Cancer
Cancers 2010, 2(4), 1884-1894; doi:10.3390/cancers2041884
Received: 28 October 2010 / Revised: 2 November 2010 / Accepted: 9 November 2010 / Published: 17 November 2010
Cited by 5 | PDF Full-text (228 KB) | HTML Full-text | XML Full-text
Abstract
The modern management of the axilla in breast cancer relies on surgery for accurate staging of disease and identifying those patients at risk who would benefit from adjuvant chemotherapy. The introduction of sentinel lymph node biopsy has revolutionized axillary surgery, but still involves
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The modern management of the axilla in breast cancer relies on surgery for accurate staging of disease and identifying those patients at risk who would benefit from adjuvant chemotherapy. The introduction of sentinel lymph node biopsy has revolutionized axillary surgery, but still involves a surgical procedure with associated morbidity in many patients with no axillary involvement. Nanotechnology encompasses a broad spectrum of scientific specialities, of which nanomedicine is one. The potential use of dual-purpose nanoprobes could enable imaging the axilla simultaneous identification and treatment of metastatic disease. Whilst most applications of nanomedicine are still largely in the laboratory phase, some potential applications are currently undergoing clinical evaluation for translation from the bench to the bedside. This is an exciting new area of research where scientific research may become a reality. Full article
(This article belongs to the Special Issue Nanotechnology and Cancer Therapeutics)

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