Light-sensitive lipid-based nanoparticles for drug delivery: design principles and future considerations for biological applications

Abstract

Radiation-based therapies aided by nanoparticles have been developed for decades, and can be primarily categorized into two main platforms. First, delivery of payload of photo-reactive drugs (photosensitizers) using the conventional nanoparticles, and second, design and development of photo-triggerable nanoparticles (primarily liposomes) to attain light-assisted on-demand drug delivery. The main focus of this review is to provide an update of the history, current status and future applications of photo-triggerable lipid-based nanoparticles (light-sensitive liposomes). We will begin with a brief overview on the applications of liposomes for delivery of photosensitizers, including the choice of photosensitizers for photodynamic therapy, as well as the currently available light sources (lasers) used for these applications. The main segment of this review will encompass the details of strategies used to develop photo-triggerable liposomes for their drug delivery function. The principles underlying the assembly of photoreactive lipids into nanoparticles (liposomes) and photo-triggering mechanisms will be presented. We will also discuss factors that limit the applications of these liposomes for in vivo triggered drug delivery and emerging concepts that may lead to the biologically viable photo-activation strategies. We will conclude with our view point on the future perspectives of light-sensitive liposomes in the clinic.     

Drug and gene delivery using gold nanoparticles

Monolayer-functionalized gold nanoparticles provide attractive vehicles for pharmaceutical delivery applications as a result of their size and the unique properties and release mechanisms imparted by their monolayer. This review provides examples of recent advances in the field of drug and gene delivery using gold nanoparticles.     

Nanoparticles and cancer therapy: Perspectives for application of nanoparticles in the treatment of cancers

Rapid growth in nanotechnology toward the development of nanomedicine agents holds massive promise to improve therapeutic approaches against cancer. Nanomedicine products represent an opportunity to achieve sophisticated targeting strategies and multifunctionality. Nowadays, nanoparticles (NPs) have multiple applications in different branches of science. In recent years, NPs have repetitively been reported to play a significant role in modern medicine. They have been analyzed for different clinical applications, such as drug carriers, gene delivery to tumors, and contrast agents in imaging. A wide range of nanomaterials based on organic, inorganic, lipid, or glycan compounds, as well as on synthetic polymers has been utilized for the development and improvement of new cancer therapeutics. In this study, we discuss the role of NPs in treating cancer among different drug delivery methods for cancer therapy.     

Biomedical applications of carbon nanomaterials: Drug and gene delivery potentials

One of the major components in the development of nanomedicines is the choice of the right biomaterial, which notably determines the subsequent biological responses. The popularity of carbon nanomaterials (CNMs) has been on the rise due to their numerous applications in the fields of drug delivery, bioimaging, tissue engineering, and biosensing. Owing to their considerably high surface area, multifunctional surface chemistry, and excellent optical activity, novel functionalized CNMs possess efficient drug-loading capacity, biocompatibility, and lack of immunogenicity. Over the past few decades, several advances have been made on the functionalization of CNMs to minimize their health concerns and enhance their biosafety. Recent evidence has also implied that CNMs can be functionalized with bioactive peptides, proteins, nucleic acids, and drugs to achieve composites with remarkably low toxicity and high pharmaceutical efficiency. This review focuses on the three main classes of CNMs, including fullerenes, graphenes, and carbon nanotubes, and their recent biomedical applications.     

核酸适配体在靶向药物传递中的研究进展

抗癌药物的毒副作用限制了其临床应用,纳米药物载体可实现药物在病灶部位的聚集而不影响正常组织,从而降低药物毒副作用.在药物载体表面修饰靶向配体,以提高药物载体主动靶向进入到细胞的能力,可有效地将药物释放到靶细胞,大大提高药效.核酸适配体(aptamer)作为一种新型的靶向分子,近几年已被运用到靶向药物传递的研究中.本文介绍了几种适配体靶向载药体系,如适配体-药物、适配体-脂质体、适配体-聚合物胶束、适配体-聚合物纳米颗粒、适配体-金属颗粒以及适配体-支化聚合物等载药体系,并对当前研究的热点以及存在的问题和不足进行了评述.     

Chitosan and lactic acid-grafted chitosan nanoparticles as carriers for prolonged drug delivery

Nanoparticles of approximately 10nm in diameter made with chitosan or lactic acid-grafted chitosan were developed for high drug loading and prolonged drug release. A drug encapsulation efficiency of 92% and a release rate of 28% from chitosan nanoparticles over a 4-week period were demonstrated with bovine serum protein. To further increase drug encapsulation, prolong drug release, and increase chitosan solubility in solution of neutral pH, chitosan was modified with lactic acid by grafting D,L-lactic acid onto amino groups in chitosan without using a catalyst. The lactic acid-grafted chitosan nanoparticles demonstrated a drug encapsulation efficiency of 96% and a protein release rate of 15% over 4 weeks. With increased protein concentration, the drug encapsulation efficiency decreased and drug release rate increased. Unlike chitosan, which is generally soluble only in acid solution, the chitosan modified with lactic acid can be prepared from solutions of neutral pH, offering an additional advantage of allowing proteins or drugs to be uniformly incorporated in the matrix structure with minimal or no denaturization.     

Controlling the thickness of polymeric shell on magnetic nanoparticles loaded with doxorubicin for targeted delivery and MRI contrast agent

The polymeric functionalization of superparamagnetic iron oxides nanoparticles is developed for cancer targeting capability and magnetic resonance imaging. Here the nanoparticles (NP) are decorated through the adsorption of a polymeric layer around the particle surface for the formation of core-shell. The synthesized magnetic nanoparticles (MNPs) are conjugated with fluorescent dye, targeting ligand, and drug molecules for improvement of target specific diagnostic and possible therapeutics applications. In this investigation doxorubicin was loaded into the shell of the MNPs and release study was carried out at different pH. The core-shell structure of magnetic NP coated chitosan matrix was visualized by TEM observation. The cytotoxicity of these magnetic NPs is investigated using MTT assay and receptor mediated internalization by HeLa and NIH3T3 cells are studied by fluorescence microscopy. Moreover, compared with T₂-weighted magnetic resonance imaging (MRI) in the above cells, the synthesized nanoparticles are showed stronger contrast enhancements towards cancer cells.     

介孔碳纳米材料的制备及其在药物传递方面的应用进展

新型功能性纳米材料在设计和制备技术方面的进步为纳米医学的发展提供了很大的机遇。在过去十年中,介孔碳纳米材料在制备和应用方面获得了巨大的进步。作为一种新型无机材料体系,介孔碳纳米材料结合了介孔的结构以及碳质组成的特点,显示出不同于传统介孔二氧化硅以及其它一些碳基材料体系(碳纳米管、石墨烯、富勒烯等)的优越特性。介孔碳纳米材料在药物的吸附与控释、光热治疗、协同治疗、肿瘤细胞的荧光标记、催化、生物传感、生物大分子的分离等诸多领域表现出其他多孔材料难以达到的优越性和应用潜力。本文对介孔碳纳米材料的制备和修饰技术进行介绍,重点关注介孔碳纳米颗粒在药物负载和光热控释方面的应用,最后对介孔碳纳米材料在生物医学领域的应用前景和所面临的关键问题进行讨论。     

Magnetic nanoparticles for gene and drug delivery

Investigations of magnetic micro- and nanoparticles for targeted drug delivery began over 30 years ago. Since that time, major progress has been made in particle design and synthesis techniques, however, very few clinical trials have taken place. Here we review advances in magnetic nanoparticle design, in vitro and animal experiments with magnetic nanoparticle-based drug and gene delivery, and clinical trials of drug targeting.     

Chitosan nanoparticles for oral drug and gene delivery

Chitosan is a widely available, mucoadhesive polymer that is able to increase cellular permeability and improve the bioavailability of orally administered protein drugs. It can also be readily formed into nanoparticles able to entrap drugs or condense plasmid DNA. Studies on the formulation and oral delivery of such chitosan nanoparticles have demonstrated their efficacy in enhancing drug uptake and promoting gene expression. This review summarizes some of these findings and highlights the potential of chitosan as a component of oral delivery systems.     

Engineered nanoparticles as precise drug delivery systems

With the remarkable development of nanotechnology in recent years, new drug delivery approaches based on the state-of-the-art nanotechnology have been receiving significant attention. Nanoparticles, an evolvement of nanotechnology, are increasingly considered as a potential candidate to carry therapeutic agents safely into a targeted compartment in an organ, particular tissue or cell. These particles are colloidal structures with a diameter smaller than 1,000 nm, and therefore can penetrate through diminutive capillaries into the cell's internal machinery. This innovative delivery technique might be a promising technology to meet the current challenges in drug delivery. When loaded with a gene or drug agent, nanoparticles can become nanopills, which can effectively treat problematical diseases such as cancer. This article summarizes different types of nanoparticles drug delivery systems under investigation and their prospective therapeutic applications. Also, this article presents a closer look at the advances, current challenges, and future direction of nanoparticles drug delivery systems.     

Inorganic Porous Nanoparticles for Drug Delivery in Antitumoral Therapy

The use of nanoparticles in oncology to deliver chemotherapeutic agents has received considerable attention in the last decades due to their tendency to be passively accumulated in solid tumors. Besides this remarkable property, the surface of these nanocarriers can be decorated with targeting moieties capable to recognize malignant cells which lead to selective nanoparticle uptake mainly in the diseased cells, without affecting the healthy ones. Among the different nanocarriers which have been developed with this purpose, inorganic porous nanomaterials constitute some of the most interesting due to their unique properties such as excellent cargo capacity, high biocompatibility and chemical, thermal and mechanical robustness, among others. Additionally, these materials can be engineered to present an exquisite control in the drug release behavior placing stimuli-responsive pore-blockers or sensitive hybrid coats on their surface. Herein, the recent advances developed in the use of porous inorganic nanomedicines will be described in order to provide an overview of their huge potential in the look out of an efficient and safe therapy against this complex disease. Porous inorganic nanoparticles have been designed to be accumulated in tumoral tissues; once there to recognize the target cell and finally, to release their payload in a controlled manner.     

AS1411 aptamer tagged PLGA-lecithin-PEG nanoparticles for tumor cell targeting and drug delivery

Liposomes and polymers are widely used drug carriers for controlled release since they offer many advantages like increased treatment effectiveness, reduced toxicity and are of biodegradable nature. In this work, anticancer drug‐loaded PLGA‐lecithin‐PEG nanoparticles (NPs) were synthesized and were functionalized with AS1411 anti‐nucleolin aptamers for site‐specific targeting against tumor cells which over expresses nucleolin receptors. The particles were characterized by transmission electron microscope (TEM) and X‐ray photoelectron spectroscopy (XPS). The drug‐loading efficiency, encapsulation efficiency and in vitro drug release studies were conducted using UV spectroscopy. Cytotoxicity studies were carried out in two different cancer cell lines, MCF‐7 and GI‐1 cells and two different normal cells, L929 cells and HMEC cells. Confocal microscopy and flowcytometry confirmed the cellular uptake of particles and targeted drug delivery. The morphology analysis of the NPs proved that the particles were smooth and spherical in shape with a size ranging from 60 to 110 nm. Drug‐loading studies indicated that under the same drug loading, the aptamer‐targeted NPs show enhanced cancer killing effect compared to the corresponding non‐targeted NPs. In addition, the PLGA‐lecithin‐PEG NPs exhibited high encapsulation efficiency and superior sustained drug release than the drug loaded in plain PLGA NPs. The results confirmed that AS1411 aptamer‐PLGA‐lecithin‐PEG NPs are potential carrier candidates for differential targeted drug delivery. Biotechnol. Bioeng. 2012; 109: 2920–2931. © 2012 Wiley Periodicals, Inc.     

Chitosan magnetic nanoparticles for drug delivery systems

The potential of magnetic nanoparticles (MNPs) in drug delivery systems (DDSs) is mainly related to its magnetic core and surface coating. These coatings can eliminate or minimize their aggregation under physiological conditions. Also, they can provide functional groups for bioconjugation to anticancer drugs and/or targeted ligands. Chitosan, as a derivative of chitin, is an attractive natural biopolymer from renewable resources with the presence of reactive amino and hydroxyl functional groups in its structure. Chitosan nanoparticles (NPs), due to their huge surface to volume ratio as compared to the chitosan in its bulk form, have outstanding physico-chemical, antimicrobial and biological properties. These unique properties make chitosan NPs a promising biopolymer for the application of DDSs. In this review, the current state and challenges for the application magnetic chitosan NPs in drug delivery systems were investigated. The present review also revisits the limitations and commercial impediments to provide insight for future works.     

层层自组装纳米粒作为非病毒基因载体

基因治疗的效果严重依赖于基因载体。与传统包封技术相比,在自组装技术基础上发展起来的以DNA为聚阴离子,与荷正电的高分子材料在溶液中形成纳米粒的方法,已成为目前最重要的非病毒基因载体制备手段,具有良好的应用前景。采用层层自组装(layer-by-layer assembly,LbL)技术可提高基因装载率,其优势还在于纳米粒表面性质的可控性:在温和的条件下实现多种材料在载体表面的固定,实现载体多功能化等。本文将对近年来国内外有关层层自组装纳米粒作为非病毒基因载体的研究进展以及本课题组在此方向的研究进行简要综述。     

Circulation and distribution of gold nanoparticles and induced alterations of tissue morphology at intravenous particle delivery

Kinetics, biodistribution, and histological studies were performed to evaluate the particle‐size effects on the distribution of 15 nm and 50 nm PEG‐coated colloidal gold (CG) particles and 160 nm silica/gold nanoshells (NSs) in rats and rabbits. The above nanoparticles (NPs) were used as a model because of their importance for current biomedical applications such as photothermal therapy, optical coherence tomography, and resonance‐scattering imaging. The dynamics of NPs circulation in vivo was evaluated after intravenous administration of 15 nm CG NPs to rabbit, and the maximal concentrations of gold were observed 15–30 min after injection. Rats were injected in the tail vein with PEG‐coated NPs (about 0.3 mg Au/kg rats). 24 h after injection, the accumulation of gold in different organs and blood was determined by atomic absorption spectroscopy. In accordance with the published reports, we observed 15 nm particles in all organs with rather smooth distribution over liver, spleen and blood. By contrast, the larger NSs were accumulated mainly in the liver and spleen. For rabbits, the biodistribution was similar (72 h after intravenous injection). We report also preliminary data on the light microscopy and TEM histological examination that allows evaluation of the changes in biotissues after gold NPs treatment. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Adriamycin release from poly(lactide-coglycolide)-polyethylene glycol nanoparticles: synthesis, and in vitro characterization

The preparation, properties, and application in adriamycin delivery ofbiocompatible and biodegradable poly(lactide-co-glycolide)-polyethylene glycol (PLGA-PEG) nanoparticles are discussed. PLGA-PEG copolymers were synthesized by ring opening polymerization of the dl-lactide and glycolide in the presence of PEG1000. 1H-NMR and FT-IR spectrum were consistent with the structure of PLGA-PEG copolymers. The adriamycin-loaded nanoparticles could be prepared using a precipitation-solvent evaporation technique. The nanoparticles have been produced by a precipitation-solvent evaporation technique. The physical characteristics and drug loading efficiency of the PLGA-PEG nanoparticles were influenced by the composition of the PLGA-PEG copolymers used to prepare the nanoparticles. Particle sizes were between 65 and 100 nm for different compositions of PLGA-PEG copolymers. PLGA-PEG nanoparticles prepared from copolymers having relatively high PLGA/PEG ratios were smaller. Entrapment efficiency was 25%-33%. Adriamycin release from the nanoparticles at pH 7.4 showed an initial burst release and then sustained release phase. These results showed that PLGA-PEG nanoparticles could be an effective carrier for cancer therapy.