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Nanomaterials
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Polymeric Micelles and Their Application in Nanomedicine
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Polymeric Micelles and Their Application in Nanomedicine

A special issue of Nanomaterials (ISSN 2079-4991).

Deadline for manuscript submissions: closed (20 April 2019) | Viewed by 20109

Special Issue Editors

Prof. Dr. Horacio Cabral

E-Mail Website
Guest Editor
Department of Bioengineering, The University of Tokyo, Tokyo, Japan
Interests: nanomedicine; mRNA delivery; immunotherapy; cancer; in vivo imaging
Special Issues, Collections and Topics in MDPI journals
Prof. Huabing Chen

E-Mail Website
Guest Editor
College of Pharmaceutical Sciences, Soochow University, Renai Road 199, Suzhou Industrial Park, Suzhou 215123, China
Interests: biomimetic synthesis of protein nanoparticles and their application in cancer theranostics; cancer-targeted polymeric nanoparticles

Special Issue Information

Dear Colleagues,

We are pleased to contact you regarding this forthcoming Special Issue in Nanomaterials, entitled “Polymeric Micelles and Their Application in Nanomedicine".

Polymeric micelles, i.e., self-assembled core-shell nanostructures of block copolymers, present outstanding features for delivering a wide range of bioactive molecules and spatiotemporally controlling their functions. The aim of this issue is to highlight advances in the development of polymeric micelles by featuring the newest trends in innovative strategies for nanomedicine applications. In this context, we would like to invite you to submit a manuscript for this Special Issue. Typically, the format of welcomed articles includes full papers, communications, and reviews. All papers will undergo regular refereeing procedures, managed by the in-house editors.

We would be delighted if you could contribute to this Special Issue.

Prof. Horacio Cabral
Prof. Huabing Chen
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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. Nanomaterials is an international peer-reviewed open access semimonthly 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 2900 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

  • block copolymers
  • drug delivery
  • gene delivery
  • imaging
  • theranostics
  • cancer therapy

Published Papers (5 papers)

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Research

10 pages, 3653 KiB  
Article
A Photocleavable Amphiphilic Prodrug Self-Assembled Nanoparticles with Effective Anticancer Activity In Vitro
by Ji Chen, Guotao Li, Qihong Liu, Yan Liang, Miaochang Liu, Huayue Wu and Wenxia Gao
Nanomaterials 2019, 9(6), 860; https://doi.org/10.3390/nano9060860 - 05 Jun 2019
Cited by 9 | Viewed by 3370
Abstract
Accelerating degradation of prodrug is an effective strategy for improving the pharmacological action. A photocleavable amphiphilic prodrug of methotrexate-coumarin derivative-PEG conjugates (MTX-AMC-PEG) with photo-triggered breakage to release clinical drug under laser irradiation was fabricated and self-assembled into nanoparticles for chemotherapy. The nanoparticles exhibited [...] Read more.
Accelerating degradation of prodrug is an effective strategy for improving the pharmacological action. A photocleavable amphiphilic prodrug of methotrexate-coumarin derivative-PEG conjugates (MTX-AMC-PEG) with photo-triggered breakage to release clinical drug under laser irradiation was fabricated and self-assembled into nanoparticles for chemotherapy. The nanoparticles exhibited good intracellular uptake and excellent photolysis release of MTX, which resulted in efficient anticancer activity in vitro with laser irradiation. This research provides a way to fabricate photocleavable prodrug nanoparticles with stimuli-triggered drug release behavior. Full article
(This article belongs to the Special Issue Polymeric Micelles and Their Application in Nanomedicine)
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18 pages, 2629 KiB  
Article
Cyclodextrin–Amphiphilic Copolymer Supramolecular Assemblies for the Ocular Delivery of Natamycin
by Blanca Lorenzo-Veiga, Hakon Hrafn Sigurdsson, Thorsteinn Loftsson and Carmen Alvarez-Lorenzo
Nanomaterials 2019, 9(5), 745; https://doi.org/10.3390/nano9050745 - 15 May 2019
Cited by 34 | Viewed by 4639
Abstract
Natamycin is the only drug approved for fungal keratitis treatment, but its low water solubility and low ocular penetration limit its efficacy. The purpose of this study was to overcome these limitations by encapsulating the drug in single or mixed micelles and poly(pseudo)rotaxanes. [...] Read more.
Natamycin is the only drug approved for fungal keratitis treatment, but its low water solubility and low ocular penetration limit its efficacy. The purpose of this study was to overcome these limitations by encapsulating the drug in single or mixed micelles and poly(pseudo)rotaxanes. Soluplus and Pluronic P103 dispersions were prepared in 0.9% NaCl and pH 6.4 buffer, with or without α-cyclodextrin (αCD; 10% w/v), and characterized through particle size, zeta potential, solubilization efficiency, rheological properties, ocular tolerance, in vitro drug diffusion, and ex vivo permeation studies. Soluplus micelles (90–103 nm) and mixed micelles (150–110 nm) were larger than Pluronic P103 ones (16–20 nm), but all showed zeta potentials close to zero. Soluplus, Pluronic P103, and their mixed micelles increased natamycin solubility up to 6.00-fold, 3.27-fold, and 2.77-fold, respectively. Soluplus dispersions and poly(pseudo)rotaxanes exhibited in situ gelling capability, and they transformed into weak gels above 30 °C. All the formulations were non-irritant according to Hen’s Egg Test on the Chorioallantoic Membrane (HET-CAM) assay. Poly(pseudo)rotaxanes facilitated drug accumulation into the cornea and sclera, but led to lower natamycin permeability through the sclera than the corresponding micelles. Poly(pseudo)rotaxanes made from mixed micelles showed intermediate natamycin diffusion coefficients and permeability values between those of Pluronic P103-based and Soluplus-based poly(pseudo)rotaxanes. Therefore, the preparation of mixed micelles may be a useful tool to regulate drug release and enhance ocular permeability. Full article
(This article belongs to the Special Issue Polymeric Micelles and Their Application in Nanomedicine)
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Graphical abstract

15 pages, 14463 KiB  
Article
PEG-Poly(1-Methyl-l-Tryptophan)-Based Polymeric Micelles as Enzymatically Activated Inhibitors of Indoleamine 2,3-Dioxygenase
by George Lo Huang, Anqi Tao, Takuya Miyazaki, Thahomina Khan, Taehun Hong, Yasuhiro Nakagawa and Horacio Cabral
Nanomaterials 2019, 9(5), 719; https://doi.org/10.3390/nano9050719 - 09 May 2019
Cited by 13 | Viewed by 4857
Abstract
Indoleamine 2,3-dioxygenase (IDO) is an immunomodulating enzyme that is overexpressed in many cancers with poor prognosis. IDO suppresses T cell immunity by catabolizing tryptophan into kynurenine (KYN), which induces apoptosis in T effector cells and enhances T regulatory cells, providing a powerful immunosuppressive [...] Read more.
Indoleamine 2,3-dioxygenase (IDO) is an immunomodulating enzyme that is overexpressed in many cancers with poor prognosis. IDO suppresses T cell immunity by catabolizing tryptophan into kynurenine (KYN), which induces apoptosis in T effector cells and enhances T regulatory cells, providing a powerful immunosuppressive mechanism in tumors. Thus, major efforts for developing IDO inhibitors have been undertaken. Among them, 1-Methyl-l-Tryptophan (MLT) and 1-Methyl-d-Tryptophan (MDT) effectively inhibit IDO in preclinical tumor models and the latter is under clinical evaluation. However, both MLT and MDT present poor pharmacokinetics, with the maximum serum concentration being below their 50% inhibitory concentration value. Herein, we have developed polymeric IDO inhibitors based on MLT, which can release active MLT after enzymatic degradation, toward establishing superior antitumor immunotherapies. These polymers were prepared by ring opening polymerization of an N-phenyl carbamate (NPC) derivative of MLT that was synthesized by carbamylation with diphenyl carbonate. By using ω-amino-poly(ethylene glycol) (PEG-NH2) as the macroinitiator, we prepared amphiphilic PEG-poly(MLT) block copolymers, which self-assembled into polymeric micelles in aqueous conditions. The PEG-poly(MLT) block copolymers could be readily degraded by chymotrypsin and the micelles were able to reduce the levels of KYN in activated macrophages. These results provide a strong rationale for pursuing MLT-based polymeric micelles as tumor-targeted prodrug systems. Full article
(This article belongs to the Special Issue Polymeric Micelles and Their Application in Nanomedicine)
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Graphical abstract

14 pages, 2351 KiB  
Article
Self-Assembling Hybrid Linear-Dendritic Block Copolymers: The Design of Nano-Carriers for Lipophilic Antitumoral Drugs
by Elisabetta Fedeli, Alexandre Lancelot, Juan Manuel Dominguez, José Luis Serrano, Pilar Calvo and Teresa Sierra
Nanomaterials 2019, 9(2), 161; https://doi.org/10.3390/nano9020161 - 29 Jan 2019
Cited by 15 | Viewed by 3666
Abstract
Two series of amphiphilic block copolymers with a hybrid linear-dendritic structure are presented. The compounds consisted of a hydrophilic poly (ethylene glycol) (PEG) block and a 2,2′-bis(hydroxymethyl)propionic acid (bis-MPA) dendron functionalized with stearic acid chains that impart a hydrophobic nature to the block. [...] Read more.
Two series of amphiphilic block copolymers with a hybrid linear-dendritic structure are presented. The compounds consisted of a hydrophilic poly (ethylene glycol) (PEG) block and a 2,2′-bis(hydroxymethyl)propionic acid (bis-MPA) dendron functionalized with stearic acid chains that impart a hydrophobic nature to the block. Different self-assembled nanostructures with a hydrophobic interior and a hydrophilic external part were obtained depending on the length of the PEG chain (Mn = 2000 and Mn = 5000) and the generation of the bis-MPA dendron. The materials were characterized by transmission electron microscopy (TEM). The shapes of the aggregates ranged from spherical or cylindrical micelles to flexible bilayers. The hydrophobic core enabled these nanostructures to encapsulate the water-insoluble drug plitidepsin. The efficacy of these new plitidepsin-containing carriers was evaluated in four cancer cell-lines and they showed similar anticancer activity to the current standard drug formulation. Full article
(This article belongs to the Special Issue Polymeric Micelles and Their Application in Nanomedicine)
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Graphical abstract

17 pages, 3363 KiB  
Article
Enhanced Anticancer Activity of 5’-DFUR-PCL-MPEG Polymeric Prodrug Micelles Encapsulating Chemotherapeutic Drugs
by Alicia J. Sawdon, Jun Zhang, Xutu Wang and Ching-An Peng
Nanomaterials 2018, 8(12), 1041; https://doi.org/10.3390/nano8121041 - 13 Dec 2018
Cited by 10 | Viewed by 3039
Abstract
The compound 5’-deoxy-5-fluorouridine (5’-DFUR) is a prodrug of the anti-tumor drug 5-fluorouracil (5-FU). Thymidine phosphorylase (TP) is an enzyme that can convert 5’-DFUR to its active form 5-FU and the expression of TP is upregulated in various cancer cells. In this study, 5’-DFUR [...] Read more.
The compound 5’-deoxy-5-fluorouridine (5’-DFUR) is a prodrug of the anti-tumor drug 5-fluorouracil (5-FU). Thymidine phosphorylase (TP) is an enzyme that can convert 5’-DFUR to its active form 5-FU and the expression of TP is upregulated in various cancer cells. In this study, 5’-DFUR associated with amphiphilic copolymer poly(ε-caprolactone)-methoxy poly(ethylene glycol) (5’-DFUR-PCL-MPEG) was synthesized, characterized, and self-assembled into functional polymeric micelles. To demonstrate that the prodrug 5’-DFUR could convert into cytotoxic 5-fluorouracil (5-FU) by endogenous TP, HT-29 colorectal cancer cells were treated with 5’-DFUR-PCL-MPEG polymeric micelles for various time periods. Chemotherapeutic drugs doxorubicin (DOX) and 7-ethyl-10-hydroxycamptothecin (SN-38) were also encapsulated separately into 5’-DFUR-PCL-MPEG polymeric micelles to create a dual drug-loaded system. HT-29 cells were treated with DOX or SN-38 encapsulated 5’-DFUR-PCL-MPEG polymeric micelles to examine the efficacy of dual drug-loaded micelles. As a result, HT-29 cells treated with 5’-DFUR-PCL-MPEG polymeric micelles showed up to 40% cell death rate after a 72-h treatment. In contrast, HT-29 cells challenged with DOX or SN-38 encapsulated 5’-DFUR-incorporated polymeric micelles showed 36% and 31% in cell viability after a 72-h treatment, respectively. Full article
(This article belongs to the Special Issue Polymeric Micelles and Their Application in Nanomedicine)
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