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Pharmaceutics
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Self-Assembling Smart Nanoparticles for Drug Delivery
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Self-Assembling Smart Nanoparticles for Drug Delivery

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 20513

Special Issue Editor

Dr. Manuela Curcio

E-Mail Website
Guest Editor
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy
Interests: design, synthesis and characterization of polymer nanoparticles and hydrogels; synthesis and characterization of stimuli-responsive micro- and nanoparticle systems for controlled drug release
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Supramolecular self-assembled structures based on lipids, proteins, and nucleic acids are involved in a variety of cell functions, such as the compartmentalization of environments, the transport of molecules, and interactions of cells with extracellular compartments. With the attempt to mimic these natural systems, a variety of self-assembling biomaterials, such as micelles, liposomes, polymeric vesicles, and dendrimers have been developed for the diagnosis and treatment of several diseases, first of all for cancer therapy. The size and shape of these systems, as well as their physic-chemical properties, can be finely tuned to optimize their performances as drug delivery vehicles. Moreover, by virtue of the better understanding of the physio-pathological pathways of cancer cells, and with the aim to improve the pharmacokinetic profile of the loaded drug, nanoparticles that able to modulate the release of the payload in response to exogenous stimuli (i.e., variations of pH, temperature, redox potential, and enzymes), or decorated with ligands of specific membrane receptors, have been proposed.

This Special Issue is devoted to the most recent developments in the synthesis and characterization of self-assembled nanoparticles that are able to program the drug release in response to external signals for cancer treatment.

Original research papers, communications, or review articles are welcome for this Special Issue.

Dr. Manuela Curcio
Guest Editor

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. 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 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

  • nanotechnology
  • self-assembled nanoparticles
  • stimuli-responsive delivery
  • targeted delivery
  • cancer therapy

Published Papers (6 papers)

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Research

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16 pages, 3339 KiB  
Article
Dual-Targeted Hyaluronic Acid/Albumin Micelle-Like Nanoparticles for the Vectorization of Doxorubicin
by Manuela Curcio, Luis Diaz-Gomez, Giuseppe Cirillo, Fiore Pasquale Nicoletta, Antonella Leggio and Francesca Iemma
Pharmaceutics 2021, 13(3), 304; https://doi.org/10.3390/pharmaceutics13030304 - 26 Feb 2021
Cited by 27 | Viewed by 2738
Abstract
Drug targeting of tumor cells is one of the great challenges in cancer therapy; nanoparticles based on natural polymers represent valuable tools to achieve this aim. The ability to respond to environmental signals from the pathological site (e.g., altered redox potential), together with [...] Read more.
Drug targeting of tumor cells is one of the great challenges in cancer therapy; nanoparticles based on natural polymers represent valuable tools to achieve this aim. The ability to respond to environmental signals from the pathological site (e.g., altered redox potential), together with the specific interaction with membrane receptors overexpressed on cancer cells membrane (e.g., CD44 receptors), represent the main features of actively targeted nanoparticles. In this work, redox-responsive micelle-like nanoparticles were prepared by self-assembling of a hyaluronic acid–human serum albumin conjugate containing cystamine moieties acting as a functional spacer. The conjugation procedure consisted of a reductive amination step of hyaluronic acid followed by condensation with albumin. After self-assembling, nanoparticles with a mean size of 70 nm and able to be destabilized in reducing media were obtained. Doxorubicin-loaded nanoparticles modulated drug release rate in response to different redox conditions. Finally, the viability and uptake experiments on healthy (BALB-3T3) and metastatic cancer (MDA-MB-231) cells proved the potential applicability of the proposed system as a drug vector in cancer therapy. Full article
(This article belongs to the Special Issue Self-Assembling Smart Nanoparticles for Drug Delivery)
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10 pages, 2451 KiB  
Article
Glucose-Responsive Gene Delivery at Physiological pH through Tertiary-Amine Stabilized Boronate-PVA Particles Synthesized by One-Pot Reaction
by Mangesh Morey, Akshay Srivastava and Abhay Pandit
Pharmaceutics 2021, 13(1), 62; https://doi.org/10.3390/pharmaceutics13010062 - 06 Jan 2021
Cited by 4 | Viewed by 2020
Abstract
We report a physiologically stable and cytocompatible glucose-responsive nonviral gene delivery system made up of boronate functionalized polymeric material. Herein, we utilize boronate cis-diol interactions to develop a glucose-responsive submicron particle (SMP) system. The stability of the boronate interaction at a physiological [...] Read more.
We report a physiologically stable and cytocompatible glucose-responsive nonviral gene delivery system made up of boronate functionalized polymeric material. Herein, we utilize boronate cis-diol interactions to develop a glucose-responsive submicron particle (SMP) system. The stability of the boronate interaction at a physiological pH was achieved by copolymerization of dimethyl aminoethyl methacrylate (DMAEMA) with acrylamidophenylboronic acid (AAPBA) and the formation of a complex with polyvinylalcohol (PVA) which is governed by cis-diol interactions. The shift in hydrodynamic diameter of SMPs was observed and correlated with increasing glucose concentrations at a physiological pH. Optimal transfection was observed for a 5 µg dose of the gaussia luciferase reporter gene in NIH3T3 cells without any adverse effect on cellular viability. The destabilization of the AAPBA–PVA complex by interacting with glucose allowed the release of encapsulated bovine serum albumin (BSA) in a glucose-responsive manner. In total, 95% of BSA was released from SMPs at a 50 mM glucose concentration after 72 h. A two-fold increase in transfection was observed in 50 mM glucose compared to that of 10 mM glucose. Full article
(This article belongs to the Special Issue Self-Assembling Smart Nanoparticles for Drug Delivery)
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18 pages, 2634 KiB  
Article
Fluorescent Dye Labeling Changes the Biodistribution of Tumor-Targeted Nanoparticles
by Patricia Álamo, Victor Pallarès, María Virtudes Céspedes, Aïda Falgàs, Julieta M. Sanchez, Naroa Serna, Laura Sánchez-García, Eric Voltà-Duràn, Gordon A. Morris, Alejandro Sánchez-Chardi, Isolda Casanova, Ramón Mangues, Esther Vazquez, Antonio Villaverde and Ugutz Unzueta
Pharmaceutics 2020, 12(11), 1004; https://doi.org/10.3390/pharmaceutics12111004 - 22 Oct 2020
Cited by 22 | Viewed by 4150
Abstract
Fluorescent dye labeling is a common strategy to analyze the fate of administered nanoparticles in living organisms. However, to which extent the labeling processes can alter the original nanoparticle biodistribution has been so far neglected. In this work, two widely used fluorescent dye [...] Read more.
Fluorescent dye labeling is a common strategy to analyze the fate of administered nanoparticles in living organisms. However, to which extent the labeling processes can alter the original nanoparticle biodistribution has been so far neglected. In this work, two widely used fluorescent dye molecules, namely, ATTO488 (ATTO) and Sulfo-Cy5 (S-Cy5), have been covalently attached to a well-characterized CXCR4-targeted self-assembling protein nanoparticle (known as T22-GFP-H6). The biodistribution of labeled T22-GFP-H6-ATTO and T22-GFP-H6-S-Cy5 nanoparticles has been then compared to that of the non-labeled nanoparticle in different CXCR4+ tumor mouse models. We observed that while parental T22-GFP-H6 nanoparticles accumulated mostly and specifically in CXCR4+ tumor cells, labeled T22-GFP-H6-ATTO and T22-GFP-H6-S-Cy5 nanoparticles showed a dramatic change in the biodistribution pattern, accumulating in non-target organs such as liver or kidney while reducing tumor targeting capacity. Therefore, the use of such labeling molecules should be avoided in target and non-target tissue uptake studies during the design and development of targeted nanoscale drug delivery systems, since their effect over the fate of the nanomaterial can lead to considerable miss-interpretations of the actual nanoparticle biodistribution. Full article
(This article belongs to the Special Issue Self-Assembling Smart Nanoparticles for Drug Delivery)
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11 pages, 2300 KiB  
Article
Engineered Human Nanoferritin Bearing the Drug Genz-644282 for Cancer Therapy
by Elisabetta Falvo, Alessandro Arcovito, Giamaica Conti, Giuseppe Cipolla, Martina Pitea, Veronica Morea, Verena Damiani, Gianluca Sala, Giulio Fracasso and Pierpaolo Ceci
Pharmaceutics 2020, 12(10), 992; https://doi.org/10.3390/pharmaceutics12100992 - 20 Oct 2020
Cited by 12 | Viewed by 2807
Abstract
Gastrointestinal tumors, including pancreatic and colorectal cancers, represent one of the greatest public health issues worldwide, leading to a million global deaths. Recent research demonstrated that the human heavy chain ferritin (HFt) can encapsulate different types of drugs in its cavity and can [...] Read more.
Gastrointestinal tumors, including pancreatic and colorectal cancers, represent one of the greatest public health issues worldwide, leading to a million global deaths. Recent research demonstrated that the human heavy chain ferritin (HFt) can encapsulate different types of drugs in its cavity and can bind to its receptor, CD71, in several solid and hematological tumors, thus highlighting the potential use of ferritin for tumor-targeting therapies. Here, we describe the development and characterization of a novel nanomedicine based on the HFt that is named The-0504. In particular, this novel system is a nano-assembly comprising an engineered version of HFt that entraps about 80 molecules of a potent, wide-spectrum, non-camptothecin topoisomerase I inhibitor (Genz-644282). The-0504 can be produced by a standardized pre-industrial process as a pure and homogeneously formulated product with favourable lyophilization properties. The preliminary anticancer activity was evaluated in cultured cancer cells and in a mouse model of pancreatic cancer. Overall results reported here make The-0504 a candidate for further preclinical development against CD-71 expressing deadly tumors. Full article
(This article belongs to the Special Issue Self-Assembling Smart Nanoparticles for Drug Delivery)
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Review

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23 pages, 3055 KiB  
Review
Nanomaterials for Protein Delivery in Anticancer Applications
by Anne Yau, Jinhyung Lee and Yupeng Chen
Pharmaceutics 2021, 13(2), 155; https://doi.org/10.3390/pharmaceutics13020155 - 25 Jan 2021
Cited by 29 | Viewed by 5148
Abstract
Nanotechnology platforms, such as nanoparticles, liposomes, dendrimers, and micelles have been studied extensively for various drug deliveries, to treat or prevent diseases by modulating physiological or pathological processes. The delivery drug molecules range from traditional small molecules to recently developed biologics, such as [...] Read more.
Nanotechnology platforms, such as nanoparticles, liposomes, dendrimers, and micelles have been studied extensively for various drug deliveries, to treat or prevent diseases by modulating physiological or pathological processes. The delivery drug molecules range from traditional small molecules to recently developed biologics, such as proteins, peptides, and nucleic acids. Among them, proteins have shown a series of advantages and potential in various therapeutic applications, such as introducing therapeutic proteins due to genetic defects, or used as nanocarriers for anticancer agents to decelerate tumor growth or control metastasis. This review discusses the existing nanoparticle delivery systems, introducing design strategies, advantages of using each system, and possible limitations. Moreover, we will examine the intracellular delivery of different protein therapeutics, such as antibodies, antigens, and gene editing proteins into the host cells to achieve anticancer effects and cancer vaccines. Finally, we explore the current applications of protein delivery in anticancer treatments. Full article
(This article belongs to the Special Issue Self-Assembling Smart Nanoparticles for Drug Delivery)
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28 pages, 4141 KiB  
Review
Molecular Modelling Guided Modulation of Molecular Shape and Charge for Design of Smart Self-Assembled Polymeric Drug Transporters
by Sousa Javan Nikkhah and Damien Thompson
Pharmaceutics 2021, 13(2), 141; https://doi.org/10.3390/pharmaceutics13020141 - 22 Jan 2021
Cited by 8 | Viewed by 2935
Abstract
Nanomedicine employs molecular materials for prevention and treatment of disease. Recently, smart nanoparticle (NP)-based drug delivery systems were developed for the advanced transport of drug molecules. Rationally engineered organic and inorganic NP platforms hold the promise of improving drug targeting, solubility, prolonged circulation, [...] Read more.
Nanomedicine employs molecular materials for prevention and treatment of disease. Recently, smart nanoparticle (NP)-based drug delivery systems were developed for the advanced transport of drug molecules. Rationally engineered organic and inorganic NP platforms hold the promise of improving drug targeting, solubility, prolonged circulation, and tissue penetration. However, despite great progress in the synthesis of NP building blocks, more interdisciplinary research is needed to understand their self-assembly and optimize their performance as smart nanocarriers. Multi-scale modeling and simulations provide a valuable ally to experiment by mapping the potential energy landscape of self-assembly, translocation, and delivery of smart drug-loaded NPs. Here, we highlight key recent advances to illustrate the concepts, methods, and applications of smart polymer-based NP drug delivery. We summarize the key design principles emerging for advanced multifunctional polymer topologies, illustrating how the unusual architecture and chemistry of dendritic polymers, self-assembling polyelectrolytes and cyclic polymers can provide exceptional drug delivery platforms. We provide a roadmap outlining the opportunities and challenges for the effective use of predictive multiscale molecular modeling techniques to accelerate the development of smart polymer-based drug delivery systems. Full article
(This article belongs to the Special Issue Self-Assembling Smart Nanoparticles for Drug Delivery)
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