Impact of PEGylated Nanoparticles on Tumor Targeted Drug Delivery

2018 ◽  
Vol 24 (28) ◽  
pp. 3283-3296 ◽  
Author(s):  
Fitya Syarifa Mozar ◽  
Ezharul Hoque Chowdhury
Keyword(s):  
Drug Delivery ◽  
Targeted Drug Delivery ◽  
Surface Characteristics ◽  
Protein Corona ◽  
Therapeutic Agents ◽  
Life Extension ◽  
Pegylated Nanoparticles ◽  
Dosing Frequency ◽  
Targeted Drug ◽  
Tumor Accumulation

PEG-functionalized nanoparticles as carriers of chemotherapeutics agents have been explored with notable successes in preclinical and clinical stages of cancer treatment, with some already approved by FDA, namely PEGylated liposomes and polymers. Half-life extension of therapeutic agents through PEGylation process improves their pharmacokinetic (PK) profiles, thereby reducing their dosing frequency. Protein corona composition of PEGylated nanoparticles (NPs) confers a tremendous influence on their surface characteristics which directly impact tumor accumulation and clearance properties of the drugs. By controlling the size and complexity of PEG molecules, as well as by attaching targeting moieties, the surface characteristics of NPs can be manipulated to improve their tumor uptake without sacrificing the circulation time. This review focuses on design and applications of PEGylated NPs for tumor targeted drug delivery in animal models and clinical setting.

scholarly journals iRGD-functionalized PEGylated nanoparticles for enhanced colon tumor accumulation and targeted drug delivery

Nanomedicine ◽  
2017 ◽  
Vol 12 (16) ◽  
pp. 1991-2006 ◽  
Author(s):  
Lijun Ma ◽  
Qiubing Chen ◽  
Panpan Ma ◽  
Moon Kwon Han ◽  
Zhigang Xu ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Targeted Drug Delivery ◽  
Colon Tumor ◽  
Pegylated Nanoparticles ◽  
Targeted Drug ◽  
Tumor Accumulation

Heat Stress and Pulsed Unfocused Ultrasound: The Viability of these Physical Approaches for Drug Delivery into Testicular Seminiferous Tubules

2020 ◽  
Vol 17 (5) ◽  
pp. 438-446 ◽  
Author(s):  
Yuanyuan Li ◽  
Mohammad Ishraq Zafar ◽  
Xiaotong Wang ◽  
Xiaofang Ding ◽  
Honggang Li
Keyword(s):  
Drug Delivery ◽  
Heat Stress ◽  
Targeted Drug Delivery ◽  
Therapeutic Agents ◽  
Seminiferous Tubules ◽  
Adult Mice ◽  
Targeted Drug ◽  
To Receive ◽  
Unfocused Ultrasound ◽  
Blood Testis Barrier

Aim: To investigate the application of Scrotal Heat Stress (SHS) and Pulsed Unfocused Ultrasound (PuFUS) to explore Blood-Testis Barrier (BTB) permeability in adult mice. Background: The BTB provides a stable microenvironment and a unique immune barrier for spermatogenesis. Meanwhile, it blocks macromolecular substances access, including therapeutic agents and antibodies, thereby it decreases the therapeutic or immunocontraception effects. Objectives: To determine the viability of these physical approaches in delivering macromolecular substances into seminiferous tubules. Material & Methods: Mice were subjected to receive single SHS intervention at 39°C, 41°C, or 43°C for 30 min. Whereas, mice received the PuFUS intervention at 1.75w/cm2, 1.25w/cm2, and 2.5w/cm2 for 2 min, 5 min, and 10 min, respectively. The Biotin and macromolecular substances (IgG, IgM, and exosomes) were separately injected into the testicular interstitium at different times following SHS or PuFUS interventions, to observe their penetration through BTB into seminiferous tubules. Results: As detected by Biotin tracer, the BTB opening started from day-2 following the SHS and lasted for more than three days, whereas the BTB opening started from 1.5h following PuFUS and lasted up to 24h. Apparent penetration of IgG, IgM, and exosomes into seminiferous tubules was observed after five days of the SHS at 43°C, but none at 39°C, or any conditions tested with PuFUS. Conclusion: The current results indicate that SHS at 43°C comparatively has the potential for delivering macromolecular substances into seminiferous tubules, whereas the PuFUS could be a novel, quick, and mild approach to open the BTB. These strategies might be useful for targeted drug delivery into testicular seminiferous tubules. However, further studies are warranted to validate our findings.

scholarly journals A pillar[5]arene-based [2]rotaxane lights up mitochondria

2016 ◽  
Vol 7 (5) ◽  
pp. 3017-3024 ◽  
Author(s):  
Guocan Yu ◽  
Dan Wu ◽  
Yang Li ◽  
Zhihua Zhang ◽  
Li Shao ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Anticancer Drugs ◽  
Targeted Drug Delivery ◽  
Therapeutic Agents ◽  
Delivery Platform ◽  
Targeted Drug ◽  
Mitochondria Targeting

Here we integrate diagnostic and therapeutic agents into a mitochondria-targeting [2]rotaxane, which can be utilized as a drug delivery platform to conjugate anticancer drugs to prepare prodrugs for efficient targeted drug delivery.

scholarly journals Recent trends on hydrogel based drug delivery systems for infectious diseases

2016 ◽  
Vol 4 (11) ◽  
pp. 1535-1553 ◽  
Author(s):  
Arti Vashist ◽  
Ajeet Kaushik ◽  
Atul Vashist ◽  
Rahul Dev Jayant ◽  
Asahi Tomitaka ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Infectious Diseases ◽  
Targeted Drug Delivery ◽  
Drug Delivery Systems ◽  
Therapeutic Agents ◽  
Delivery Systems ◽  
Recent Trends ◽  
Targeted Drug ◽  
Targeted Drug Delivery Systems

Hydrogel based drug delivery systems owe excellent potential as targeted drug delivery systems for the delivery of therapeutic agents and diagnostics for major infectious diseases.

scholarly journals Cloaking nanoparticles with protein corona shield for targeted drug delivery

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Jun Yong Oh ◽  
Han Sol Kim ◽  
L. Palanikumar ◽  
Eun Min Go ◽  
Batakrishna Jana ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Targeted Drug Delivery ◽  
Protein Corona ◽  
Targeted Drug

scholarly journals Understanding the Factors Influencing Chitosan-Based Nanoparticles-Protein Corona Interaction and Drug Delivery Applications

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4758
Author(s):  
Cristina Moraru ◽  
Manuela Mincea ◽  
Gheorghita Menghiu ◽  
Vasile Ostafe
Keyword(s):  
Drug Delivery ◽  
Targeted Drug Delivery ◽  
Biological Fluids ◽  
Chemical Properties ◽  
Protein Corona ◽  
Target Cells ◽  
Major Application ◽  
Targeted Drug ◽  
Drug Delivery Applications

Chitosan is a polymer that is extensively used to prepare nanoparticles (NPs) with tailored properties for applications in many fields of human activities. Among them, targeted drug delivery, especially when cancer therapy is the main interest, is a major application of chitosan-based NPs. Due to its positive charges, chitosan is used to produce the core of the NPs or to cover NPs made from other types of polymers, both strategies aiming to protect the carried drug until NPs reach the target sites and to facilitate the uptake and drug delivery into these cells. A major challenge in the design of these chitosan-based NPs is the formation of a protein corona (PC) upon contact with biological fluids. The composition of the PC can, to some extent, be modulated depending on the size, shape, electrical charge and hydrophobic/hydrophilic characteristics of the NPs. According to the composition of the biological fluids that have to be crossed during the journey of the drug-loaded NPs towards the target cells, the surface of these particles can be changed by covering their core with various types of polymers or with functionalized polymers carrying some special molecules, that will preferentially adsorb some proteins in their PC. The PC’s composition may change by continuous processes of adsorption and desorption, depending on the affinity of these proteins for the chemical structure of the surface of NPs. Beside these, in designing the targeted drug delivery NPs one can take into account their toxicity, initiation of an immune response, participation (enhancement or inhibition) in certain metabolic pathways or chemical processes like reactive oxygen species, type of endocytosis of target cells, and many others. There are cases in which these processes seem to require antagonistic properties of nanoparticles. Products that show good behavior in cell cultures may lead to poor in vivo results, when the composition of the formed PC is totally different. This paper reviews the physico-chemical properties, cellular uptake and drug delivery applications of chitosan-based nanoparticles, specifying the factors that contribute to the success of the targeted drug delivery. Furthermore, we highlight the role of the protein corona formed around the NP in its intercellular fate.

Time Evolution of Nanoparticle–Protein Corona in Human Plasma: Relevance for Targeted Drug Delivery

Langmuir ◽  
2013 ◽  
Vol 29 (21) ◽  
pp. 6485-6494 ◽  
Author(s):  
Ana Lilia Barrán-Berdón ◽  
Daniela Pozzi ◽  
Giulio Caracciolo ◽  
Anna Laura Capriotti ◽  
Giuseppe Caruso ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Human Plasma ◽  
Time Evolution ◽  
Targeted Drug Delivery ◽  
Protein Corona ◽  
Targeted Drug

scholarly journals Brain-targeted drug delivery by manipulating protein corona functions

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Zui Zhang ◽  
Juan Guan ◽  
Zhuxuan Jiang ◽  
Yang Yang ◽  
Jican Liu ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Targeted Drug Delivery ◽  
Protein Corona ◽  
Targeted Drug

scholarly journals Novel brain-targeted nanomicelles for anti-glioma therapy mediated by the ApoE-enriched protein corona in vivo

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhe-Ao Zhang ◽  
Xin Xin ◽  
Chao Liu ◽  
Yan-hong Liu ◽  
Hong-Xia Duan ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Targeted Drug Delivery ◽  
Protein Corona ◽  
Lipid Binding ◽  
Binding Domain ◽  
Amyloid Β Protein ◽  
Blood Brain ◽  
Targeted Drug

Abstract Background The interactions between nanoparticles (NPs) and plasma proteins form a protein corona around NPs after entering the biological environment, which provides new biological properties to NPs and mediates their interactions with cells and biological barriers. Given the inevitable interactions, we regard nanoparticle‒protein interactions as a tool for designing protein corona-mediated drug delivery systems. Herein, we demonstrate the successful application of protein corona-mediated brain-targeted nanomicelles in the treatment of glioma, loading them with paclitaxel (PTX), and decorating them with amyloid β-protein (Aβ)-CN peptide (PTX/Aβ-CN-PMs). Aβ-CN peptide, like the Aβ1–42 peptide, specifically binds to the lipid-binding domain of apolipoprotein E (ApoE) in vivo to form the ApoE-enriched protein corona surrounding Aβ-CN-PMs (ApoE/PTX/Aβ-CN-PMs). The receptor-binding domain of the ApoE then combines with low-density lipoprotein receptor (LDLr) and LDLr-related protein 1 receptor (LRP1r) expressed in the blood–brain barrier and glioma, effectively mediating brain-targeted delivery. Methods PTX/Aβ-CN-PMs were prepared using a film hydration method with sonication, which was simple and feasible. The specific formation of the ApoE-enriched protein corona around nanoparticles was characterized by Western blotting analysis and LC–MS/MS. The in vitro physicochemical properties and in vivo anti-glioma effects of PTX/Aβ-CN-PMs were also well studied. Results The average size and zeta potential of PTX/Aβ-CN-PMs and ApoE/PTX/Aβ-CN-PMs were 103.1 nm, 172.3 nm, 7.23 mV, and 0.715 mV, respectively. PTX was efficiently loaded into PTX/Aβ-CN-PMs, and the PTX release from rhApoE/PTX/Aβ-CN-PMs exhibited a sustained-release pattern in vitro. The formation of the ApoE-enriched protein corona significantly improved the cellular uptake of Aβ-CN-PMs on C6 cells and human umbilical vein endothelial cells (HUVECs) and enhanced permeability to the blood–brain tumor barrier in vitro. Meanwhile, PTX/Aβ-CN-PMs with ApoE-enriched protein corona had a greater ability to inhibit cell proliferation and induce cell apoptosis than taxol. Importantly, PTX/Aβ-CN-PMs exhibited better anti-glioma effects and tissue distribution profile with rapid accumulation in glioma tissues in vivo and prolonged median survival of glioma-bearing mice compared to those associated with PMs without the ApoE protein corona. Conclusions The designed PTX/Aβ-CN-PMs exhibited significantly enhanced anti-glioma efficacy. Importantly, this study provided a strategy for the rational design of a protein corona-based brain-targeted drug delivery system. More crucially, we utilized the unfavorable side of the protein corona and converted it into an advantage to achieve brain-targeted drug delivery. Graphical Abstract

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