Special Issue "Nanotechnology Advances in Cancer Treatment"

A special issue of Pharmaceutics (ISSN 1999-4923).

Deadline for manuscript submissions: closed (10 April 2018).

Special Issue Editors

Dr. Dimitrios A. Lamprou
E-Mail Website
Guest Editor
School of Pharmacy, Queen’s University Belfast, Belfast, UK
Interests: Additive Manufacturing; 3D printing & Bioprinting; Electrospinning (melt & solution); Microfluidics & Microfluidic Devices
Special Issues and Collections in MDPI journals
Prof. Dr. Dennis Douroumis
E-Mail Website
Guest Editor
Faculty of Engineering and Science, University of Greenwich, Chatham,Kent ME4 4TB, UK
Interests: 2D/3D printing and bioprinting for regeneretive medicine; medical devices; continuous manufacturing; nanotechnology
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

Over the course of the 20th century, formulations for drug delivery began to slowly move from traditional multicomponent microtechnology-based systems to multicomponent nanotechnology-based systems. Now, in the 21st century, multicomponent nanotechnology-based systems are firmly established as the future of drug delivery within pharmaceutical sciences for a number of reasons, including greater control of drug release rates, targeted drug delivery and greater ease at overcoming both physicochemical and physiological barriers to drug absorption compared with traditional systems.

Nanotechnologies offer potentially massive benefits to society, the environment and health, since they can help us improve our quality of life and have better diagnoses and treatment of diseases. Nanocarriers for drug delivery have been an active area of research, and formulation is a cross-discipline activity requiring multiple skills to ensure that the required product performance is achieved by the judicious combination and control of active ingredient, excipients and manufacturing process.

This Special Issue will address new developments in the area of nanotechnology for cancer drug delivery, covering recent advantages and future directions on nano-based systems targeting cancer.

Preference will be awarded to papers that demonstrate contributions from scientists that provide interdisciplinary approaches to understanding pharmaceutical processing and drug delivery for cancer treatment. Original research papers and review articles are welcomed.

Dr. Dimitrios A. Lamprou
Prof. Dr. Dennis Douroumis
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Active and passive targeting

  • Bioconjugation

  • Cancer treatment

  • Formulation

  • Encapsulation

  • High pressure homogenization

  • Liposomes

  • Nanoparticles

  • Nanomedicine

  • Solid solutions

  • Solid lipid nanoparticles

Published Papers (9 papers)

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Research

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Open AccessArticle
Designing of the Anticancer Nanocomposite with Sustained Release Properties by Using Graphene Oxide Nanocarrier with Phenethyl Isothiocyanate as Anticancer Agent
Pharmaceutics 2018, 10(3), 109; https://doi.org/10.3390/pharmaceutics10030109 - 01 Aug 2018
Cited by 4
Abstract
In this study anticancer nanocomposite was designed using graphene oxide (GO) as nanocarrier and Phenethyl isothiocyanate (PEITC) as anticancer agent. The designed formulation was characterized in detailed with XRD, Raman, UV/Vis, FTIR, DLS and TEM etc. The designed anticancer nanocomposite showed much better [...] Read more.
In this study anticancer nanocomposite was designed using graphene oxide (GO) as nanocarrier and Phenethyl isothiocyanate (PEITC) as anticancer agent. The designed formulation was characterized in detailed with XRD, Raman, UV/Vis, FTIR, DLS and TEM etc. The designed anticancer nanocomposite showed much better anticancer activity against liver cancer HepG2 cells compared to the free drug PEITC and was also found to be nontoxic to the normal 3T3 cells. In vitro release of the drug from the anticancer nanocomposite formulation was found to be sustained in human body simulated phosphate buffer saline (PBS) solution of pH 7.4 (blood pH) and pH 4.8 (intracellular lysosomal pH). This study suggests that GO could be developed as an efficient drug carrier to conjugate with PEITC for pharmaceutical applications in cancer chemotherapies. Full article
(This article belongs to the Special Issue Nanotechnology Advances in Cancer Treatment)
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Open AccessArticle
Dual Acting Polymeric Nano-Aggregates for Liver Cancer Therapy
Pharmaceutics 2018, 10(2), 63; https://doi.org/10.3390/pharmaceutics10020063 - 26 May 2018
Cited by 2
Abstract
Liver cancer treatments are often hindered by poor drug physicochemical properties, hence there is a need for improvement in order to increase patient survival and outlook. Combination therapies have been studied in order to evaluate whether increased overall efficacy can be achieved. This [...] Read more.
Liver cancer treatments are often hindered by poor drug physicochemical properties, hence there is a need for improvement in order to increase patient survival and outlook. Combination therapies have been studied in order to evaluate whether increased overall efficacy can be achieved. This study reports the combined treatment of liver cancer cells with a combination treatment of chemotherapeutic agent paclitaxel and pro-apoptotic protein cytochrome C. In order to administer both agents in a single formulation, a poly(allylamine)-based amphiphile has been fabricated with the incorporation of a hybrid iron oxide-gold nanoparticle into its structure. Here, the insoluble paclitaxel becomes incorporated into the hydrophobic core of the self-assemblies formed in an aqueous environment (256 nm), while the cytochrome C attaches irreversibly onto the hybrid nanoparticle surface via gold-thiol dative covalent binding. The self-assemblies were capable of solubilising up to 0.698 mg/mL of paclitaxel (700-fold improvement) with 0.012 mg/mL of cytochrome C also attached onto the hybrid iron oxide-gold nanoparticles (HNPs) within the hydrophobic core. The formulation was tested on a panel of liver cancer cells and cytotoxicity was measured. The findings suggested that indeed a significant improvement in combined therapy (33-fold) was observed when compared with free drug, which was double the enhancement observed after polymer encapsulation without the cytochrome C in hepatocellular carcinoma (Huh-7D12) cells. Most excitingly, the polymeric nanoparticles did result in improved cellular toxicity in human endothelian liver cancer (SK-hep1) cells, which proved completely resistant to the free drug. Full article
(This article belongs to the Special Issue Nanotechnology Advances in Cancer Treatment)
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Open AccessArticle
Combined Effect of Anticancer Agents and Cytochrome C Decorated Hybrid Nanoparticles for Liver Cancer Therapy
Pharmaceutics 2018, 10(2), 48; https://doi.org/10.3390/pharmaceutics10020048 - 12 Apr 2018
Cited by 4
Abstract
Hepatocellular carcinoma is an aggressive form of liver cancer that displays minimal symptoms until its late stages. Unfortunately, patient prognosis still remains poor with only 10% of patients surviving more than five years after diagnosis. Current chemotherapies alone are not offering efficient treatment, [...] Read more.
Hepatocellular carcinoma is an aggressive form of liver cancer that displays minimal symptoms until its late stages. Unfortunately, patient prognosis still remains poor with only 10% of patients surviving more than five years after diagnosis. Current chemotherapies alone are not offering efficient treatment, hence alternative therapeutic approaches are urgently required. In this work, we highlight the potential of combination of treatment of hepatocellular carcinoma with existing chemotherapies in combination with pro-apoptotic factor cytochrome C. In order to allow cytochrome C to cross the cellular membrane and become internalized, it has been immobilised onto the surface of hybrid iron oxide-gold nanoparticles. This novel approach has been tested in vitro on HepG2, Huh-7D and SK-hep-1 cell lines in order to elucidate potential as a possible alternative therapy with greater efficacy. The data from our studies show consistently that combining treatment of clinically used anticancer agents (doxorubicin, paclitaxel, oxaliplatin, vinblastine and vincristine) significantly increases the levels of apoptosis within the cell lines, which leads to cellular death. Hence, this combined approach may hold promise for future treatment regimes. Full article
(This article belongs to the Special Issue Nanotechnology Advances in Cancer Treatment)
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Open AccessArticle
Hyaluronic Acid Decorated Naringenin Nanoparticles: Appraisal of Chemopreventive and Curative Potential for Lung Cancer
Pharmaceutics 2018, 10(1), 33; https://doi.org/10.3390/pharmaceutics10010033 - 12 Mar 2018
Cited by 19
Abstract
Lung carcinoma is the most common cancer in men and second in women (preceded by breast cancer) worldwide. Around 1 in 10 of all cancers diagnosed in men, lung cancer contributed to a total fraction of 20% cancer deaths. Naringenin (NAR) is well [...] Read more.
Lung carcinoma is the most common cancer in men and second in women (preceded by breast cancer) worldwide. Around 1 in 10 of all cancers diagnosed in men, lung cancer contributed to a total fraction of 20% cancer deaths. Naringenin (NAR) is well known for its chemopreventive properties since ancient times but lacks an appropriate delivery carrier. The objective of present study was to expand the functionality of naringenin loaded poly caprolactone (PCL) nanoparticles in terms of release, chemoprevention and therapeutics. Polymeric nanoparticles such as PCL lack target specificity; hence, surface modification was attempted using layer by layer technique (LBL) to achieve improved and desired delivery as well as target specificity. The designing of Hyaluronic acid (HA) decorated PCL nanoparticles were prepared by utilizing self-assembling LBL technique, where a polycationic layer of a polymer was used as a linker for modification between two polyanionic layers. Additionally, an attempt has been made to strengthen the therapeutic efficacy of PCL nanocarriers by active targeting and overcoming the extracellular matrix associated barriers of tumors using HA targeting cluster determinant 44 receptor (CD44). Cell cytotoxicity study on A549 cells and J774 macrophage cells depicted enhanced anticancer effect of [email protected] with safe profile on macrophages. Uptake study on A549 cells advocated enhanced drug uptake by cancer cells. Cell cycle arrest analysis (A549 cell lines) demonstrated the superior cytotoxic effect and active targeting of [email protected] Further chemopreventive treatment with [email protected] was found effective in tumor growth inhibitory effect against urethane-induced lung cancer in rat. In conclusion, developed formulation possesses a promising potential as a therapeutic and chemopreventive agent against urethane-induced lung carcinoma in albino wistar rats. Full article
(This article belongs to the Special Issue Nanotechnology Advances in Cancer Treatment)
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Open AccessArticle
Citrate- and Succinate-Modified Carbonate Apatite Nanoparticles with Loaded Doxorubicin Exhibit Potent Anticancer Activity against Breast Cancer Cells
Pharmaceutics 2018, 10(1), 32; https://doi.org/10.3390/pharmaceutics10010032 - 11 Mar 2018
Cited by 3
Abstract
Biodegradable inorganic apatite-based particle complex is popular for its pH-sensitivity at the endosomal acidic environment to facilitate drug release following cellular uptake. Despite being a powerful anticancer drug, doxorubicin shows severe off-target effects and therefore would need a carrier for the highest effectiveness. [...] Read more.
Biodegradable inorganic apatite-based particle complex is popular for its pH-sensitivity at the endosomal acidic environment to facilitate drug release following cellular uptake. Despite being a powerful anticancer drug, doxorubicin shows severe off-target effects and therefore would need a carrier for the highest effectiveness. We aimed to chemically modify carbonate apatite (CA) with Krebs cycle intermediates, such as citrate and succinate in order to control the growth of the resultant particles to more efficiently carry and transport the anticancer drug into the cancer cells. Citrate- or succinate-modified CA particles were synthesized with different concentrations of sodium citrate or sodium succinate, respectively, in the absence or presence of doxorubicin. The drug loading efficiency of the particles and their cellular uptake were observed by quantifying fluorescence intensity. The average diameter and surface charge of the particles were determined using Zetasizer. Cell viability was assessed by MTT assay. Citrate-modified carbonate apatite (CMCA) exhibited the highest (31.38%) binding affinity for doxorubicin and promoted rapid cellular uptake of the drug, leading to the half-maximal inhibitory concentration 1000 times less than that of the free drug in MCF-7 cells. Hence, CMCA nanoparticles with greater surface area enhance cytotoxicity in different breast cancer cells by enabling higher loading and more efficient cellular uptake of the drug. Full article
(This article belongs to the Special Issue Nanotechnology Advances in Cancer Treatment)
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Open AccessArticle
Folate Decorated Nanomicelles Loaded with a Potent Curcumin Analogue for Targeting Retinoblastoma
Pharmaceutics 2017, 9(2), 15; https://doi.org/10.3390/pharmaceutics9020015 - 18 Apr 2017
Cited by 15
Abstract
The aim of this study was to develop a novel folate receptor-targeted drug delivery system for retinoblastoma cells using a promising anticancer agent, curcumin-difluorinated (CDF), loaded in polymeric micelles. Folic acid was used as a targeting moiety to enhance the targeting and bioavailability [...] Read more.
The aim of this study was to develop a novel folate receptor-targeted drug delivery system for retinoblastoma cells using a promising anticancer agent, curcumin-difluorinated (CDF), loaded in polymeric micelles. Folic acid was used as a targeting moiety to enhance the targeting and bioavailability of CDF. For this purpose, amphiphilic poly(styrene-co-maleic acid)-conjugated-folic acid (SMA-FA) was synthesized and utilized to improve the aqueous solubility of a highly hydrophobic, but very potent anticancer compound, CDF, and its targeted delivery to folate overexpressing cancers. The SMA-FA conjugate was first synthesized and characterized by 1H NMR, FTIR and DSC. Furthermore, the chromatographic condition (HPLC) for estimating CDF was determined and validated. The formulation was optimized to achieve maximum entrapment of CDF. The particle size of the micelles was measured and confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Cytotoxicity studies were conducted on (Y-79 and WERI-RB) retinoblastoma cells. Results showed that the solubility of CDF could be increased with the newly-synthesized polymer, and the entrapment efficiency was >85%. The drug-loaded nanomicelles exhibited an appropriate size of <200 nm and a narrow size distribution. The formulation did not show any adverse cytotoxicity on a human retinal pigment epithelial cell (ARPE-19), indicating its safety. However, it showed significant cell killing activity in both Y-79 and WERI-RB retinoblastoma cell lines, indicating its potency in killing cancer cells. In conclusion, the folic acid-conjugated SMA loaded with CDF showed promising potential with high safety and pronounced anticancer activity on the tested retinoblastoma cell lines. The newly-formulated targeted nanomicelles thus could be a viable option as an alternative approach to current retinoblastoma therapies. Full article
(This article belongs to the Special Issue Nanotechnology Advances in Cancer Treatment)
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Review

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Open AccessReview
GE11 Peptide as an Active Targeting Agent in Antitumor Therapy: A Minireview
Pharmaceutics 2018, 10(1), 2; https://doi.org/10.3390/pharmaceutics10010002 - 22 Dec 2017
Cited by 9
Abstract
A lot of solid tumors are characterized by uncontrolled signal transduction triggered by receptors related to cellular growth. The targeting of these cell receptors with antitumor drugs is essential to improve chemotherapy efficacy. This can be achieved by conjugation of an active targeting [...] Read more.
A lot of solid tumors are characterized by uncontrolled signal transduction triggered by receptors related to cellular growth. The targeting of these cell receptors with antitumor drugs is essential to improve chemotherapy efficacy. This can be achieved by conjugation of an active targeting agent to the polymer portion of a colloidal drug delivery system loaded with an antitumor drug. The goal of this minireview is to report and discuss some recent results in epidermal growth factor receptor targeting by the GE11 peptide combined with colloidal drug delivery systems as smart carriers for antitumor drugs. The minireview chapters will focus on explaining and discussing: (i) Epidermal growth factor receptor (EGFR) structures and functions; (ii) GE11 structure and biologic activity; (iii) examples of GE11 conjugation and GE11-conjugated drug delivery systems. The rationale is to contribute in gathering information on the topic of active targeting to tumors. A case study is introduced, involving research on tumor cell targeting by the GE11 peptide combined with polymer nanoparticles. Full article
(This article belongs to the Special Issue Nanotechnology Advances in Cancer Treatment)
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Open AccessReview
Targeting Strategies for the Combination Treatment of Cancer Using Drug Delivery Systems
Pharmaceutics 2017, 9(4), 46; https://doi.org/10.3390/pharmaceutics9040046 - 14 Oct 2017
Cited by 36
Abstract
Cancer cells have characteristics of acquired and intrinsic resistances to chemotherapy treatment—due to the hostile tumor microenvironment—that create a significant challenge for effective therapeutic regimens. Multidrug resistance, collateral toxicity to normal cells, and detrimental systemic side effects present significant obstacles, necessitating alternative and [...] Read more.
Cancer cells have characteristics of acquired and intrinsic resistances to chemotherapy treatment—due to the hostile tumor microenvironment—that create a significant challenge for effective therapeutic regimens. Multidrug resistance, collateral toxicity to normal cells, and detrimental systemic side effects present significant obstacles, necessitating alternative and safer treatment strategies. Traditional administration of chemotherapeutics has demonstrated minimal success due to the non-specificity of action, uptake and rapid clearance by the immune system, and subsequent metabolic alteration and poor tumor penetration. Nanomedicine can provide a more effective approach to targeting cancer by focusing on the vascular, tissue, and cellular characteristics that are unique to solid tumors. Targeted methods of treatment using nanoparticles can decrease the likelihood of resistant clonal populations of cancerous cells. Dual encapsulation of chemotherapeutic drug allows simultaneous targeting of more than one characteristic of the tumor. Several first-generation, non-targeted nanomedicines have received clinical approval starting with Doxil® in 1995. However, more than two decades later, second-generation or targeted nanomedicines have yet to be approved for treatment despite promising results in pre-clinical studies. This review highlights recent studies using targeted nanoparticles for cancer treatment focusing on approaches that target either the tumor vasculature (referred to as ‘vascular targeting’), the tumor microenvironment (‘tissue targeting’) or the individual cancer cells (‘cellular targeting’). Recent studies combining these different targeting methods are also discussed in this review. Finally, this review summarizes some of the reasons for the lack of clinical success in the field of targeted nanomedicines. Full article
(This article belongs to the Special Issue Nanotechnology Advances in Cancer Treatment)
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Open AccessFeature PaperReview
Nanotechnologies in Pancreatic Cancer Therapy
Pharmaceutics 2017, 9(4), 39; https://doi.org/10.3390/pharmaceutics9040039 - 25 Sep 2017
Cited by 9
Abstract
Pancreatic cancer has been classified as a cancer of unmet need. After diagnosis the patient prognosis is dismal with few surviving over 5 years. Treatment regimes are highly patient variable and often the patients are too sick to undergo surgical resection or chemotherapy. [...] Read more.
Pancreatic cancer has been classified as a cancer of unmet need. After diagnosis the patient prognosis is dismal with few surviving over 5 years. Treatment regimes are highly patient variable and often the patients are too sick to undergo surgical resection or chemotherapy. These chemotherapies are not effective often because patients are diagnosed at late stages and tumour metastasis has occurred. Nanotechnology can be used in order to formulate potent anticancer agents to improve their physicochemical properties such as poor aqueous solubility or prolong circulation times after administration resulting in improved efficacy. Studies have reported the use of nanotechnologies to improve the efficacy of gemcitabine (the current first line treatment) as well as investigating the potential of using other drug molecules which have previously shown promise but were unable to be utilised due to the inability to administer through appropriate routes—often related to solubility. Of the nanotechnologies reported, many can offer site specific targeting to the site of action as well as a plethora of other multifunctional properties such as image guidance and controlled release. This review focuses on the use of the major nanotechnologies both under pre-clinical development and those which have recently been approved for use in pancreatic cancer therapy. Full article
(This article belongs to the Special Issue Nanotechnology Advances in Cancer Treatment)
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