Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
8.1
4.9
Journals
IJMS
Special Issues
Lipoprotein Nanoparticles for Diagnosis and Therapy
ijms-logo
Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

Lipoprotein Nanoparticles for Diagnosis and Therapy

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Materials Science".

Deadline for manuscript submissions: closed (31 December 2019) | Viewed by 42499

Special Issue Editors

Prof. Andras G. Lacko

E-Mail Website
Guest Editor
Departments of Physiology/Anatomy and Pediatrics, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX 76107, USA
Interests: lipoprotein (structure, function, and metabolism); drug delivery; optimization of therapeutic payload delivery; lipoprotein mimetics; apolipoprotein mimetics; anticancer drugs
Special Issues, Collections and Topics in MDPI journals
Dr. Sangram Raut

E-Mail Website
Guest Editor
Departments of Physiology/Anatomy and Pediatrics, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth Texas 76107, USA
Interests: HDL mimetic nanoparticles; HDL and Imaging; SR-B1 Receptors; LRP family receptors; cancer; neurodegenerative disorders

Special Issue Information

Dear Colleagues,

Lipoprotein-based drug delivery has been pursued by several research groups since the 1980s.  Nevertheless, despite many advantages over existing technologies, no lipoprotein-based formulation appears close to be tested in clinical trials. Significant research efforts on rHDL are involved in atherosclerosis treatment. Moreover,  synthetic lipoproteins (rHDL and rLDL) have been utilized in targeting various malignancies (e.g. cancer) of various tissues including but not limited to adrenal, testes, ovary, liver, pancreas, breast, prostate and brain in animal models. Moreover, owing to their inflammatory and antioxidant properties, these nanoparticles have become relevant in inflammatory and diseases originating due to oxidative stress. HDL and Apo-A1 is known to play critical role in immunity as well. Several reports have implicated rHDL nanoparticles for therapy of neurodegenerative diseases such as Alzheimer's. Considering the wide array of applications of these mimics of endogenous HDL,  this special edition titled “Lipoprotein Nanoparticles for Diagnosis and Therapy” of  the International Journal of Molecular Sciences is  intended to explore the paths for overcoming current barriers to the delivery of anti-cancer agents using reconstituted HDL or HDL mime tics by reporting on the latest developments on by the leading research groups in this area.

Prof. Dr. Andras G. Lacko
Dr. Sangram Raut
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • Recent advances HDL and HDL mimetic nanoparticles
  • Tumor selective delivery
  • Tumor imaging
  • Specific therapeutic applications
  • Challenges to overcome for translation
  • HDL and antioxidant properties
  • Apolipoproteins and inflammatory properties

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue policies can be found here.

Published Papers (7 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

18 pages, 5193 KiB  
Article
ABCA1/ApoE/HDL Signaling Pathway Facilitates Myelination and Oligodendrogenesis after Stroke
by Li Li, Rongwen Li, Alex Zacharek, Fengjie Wang, Julie Landschoot-Ward, Michael Chopp, Jieli Chen and Xu Cui
Int. J. Mol. Sci. 2020, 21(12), 4369; https://doi.org/10.3390/ijms21124369 - 19 Jun 2020
Cited by 35 | Viewed by 4691
Abstract
ATP-binding cassette transporter A1 (ABCA1) plays an important role in the regulation of apolipoprotein E (ApoE) and the biogenesis of high-density lipoprotein (HDL) cholesterol in the mammalian brain. Cholesterol is a major source for myelination. Here, we investigate whether ABCA1/ApoE/HDL contribute to myelin [...] Read more.
ATP-binding cassette transporter A1 (ABCA1) plays an important role in the regulation of apolipoprotein E (ApoE) and the biogenesis of high-density lipoprotein (HDL) cholesterol in the mammalian brain. Cholesterol is a major source for myelination. Here, we investigate whether ABCA1/ApoE/HDL contribute to myelin repair and oligodendrogenesis in the ischemic brain after stroke. Specific brain ABCA1-deficient (ABCA1-B/-B) and ABCA1-floxed (ABCA1fl/fl) control mice were subjected to permanent distal middle-cerebral-artery occlusion (dMCAo) and were intracerebrally administered (1) artificial mouse cerebrospinal fluid (CSF) as vehicle control, (2) human plasma HDL3, and (3) recombined human ApoE2 starting 24 h after dMCAo for 14 days. All stroke mice were sacrificed 21 days after dMCAo. The ABCA1-B/-B–dMCAo mice exhibit significantly reduced myelination and oligodendrogenesis in the ischemic brain as well as decreased functional outcome 21 days after stroke compared with ABCA1fl/fl mice; administration of human ApoE2 or HDL3 in the ischemic brain significantly attenuates the deficits in myelination and oligodendrogenesis in ABCA1-B/-B–dMCAo mice ( p < 0.05, n = 9/group). In vitro, ABCA1-B/-B reduces ApoE expression and decreases primary oligodendrocyte progenitor cell (OPC) migration and oligodendrocyte maturation; HDL3 and ApoE2 treatment significantly reverses ABCA1-B/-B-induced reduction in OPC migration and oligodendrocyte maturation. Our data indicate that the ABCA1/ApoE/HDL signaling pathway contributes to myelination and oligodendrogenesis in the ischemic brain after stroke. Full article
(This article belongs to the Special Issue Lipoprotein Nanoparticles for Diagnosis and Therapy)
►▼ Show Figures

Figure 1

11 pages, 3959 KiB  
Article
Synthetic HDL Nanoparticles Delivering Docetaxel and CpG for Chemoimmunotherapy of Colon Adenocarcinoma
by Lindsay M. Scheetz, Minzhi Yu, Dan Li, María G. Castro, James J. Moon and Anna Schwendeman
Int. J. Mol. Sci. 2020, 21(5), 1777; https://doi.org/10.3390/ijms21051777 - 5 Mar 2020
Cited by 27 | Viewed by 5509
Abstract
Colon carcinomas comprise over two-thirds of all colorectal cancers with an overall 5-year survival rate of 64%, which rapidly decreases to 14% when the cancer becomes metastatic. Depending on the stage of colon carcinoma at diagnosis, patients can undergo surgery to attempt complete [...] Read more.
Colon carcinomas comprise over two-thirds of all colorectal cancers with an overall 5-year survival rate of 64%, which rapidly decreases to 14% when the cancer becomes metastatic. Depending on the stage of colon carcinoma at diagnosis, patients can undergo surgery to attempt complete tumor resection or move directly to chemotherapy with one or a combination of drugs. As with most cancers, colon carcinomas do not always respond to chemotherapies, so targeted therapies and immunotherapies have been developed to aid chemotherapy. We report the development of a local combination therapy for colon carcinoma whereby chemo- and immunotherapeutic entities are delivered intratumorally to maximize efficacy and minimize off-target side effects. A hydrophobic chemotherapeutic agent, docetaxel (DTX), and cholesterol-modified Toll-like receptor 9 (TLR9) agonist CpG (cho-CpG) oligonucleotide are co-loaded in synthetic HDL (sHDL) nanodiscs. In vivo survival analysis of MC-38 tumor-bearing mice treated intratumorally with DTX-sHDL/CpG (median survival; MS = 43 days) showed significant improvement in overall survival compared to mice treated with single agents, free DTX (MS = 23 days, p < 0.0001) or DTX-sHDL (MS = 28 days, p < 0.0001). Two of seven mice treated with DTX-sHDL/CpG experienced complete tumor regression. None of the mice experienced any systemic toxicity as indicated by body weight maintenance and normal serum enzyme and protein levels. In summary, we have demonstrated that chemo- and immunotherapies can be co-loaded into sHDLs, delivered locally to the tumor, and can be used to improve survival outcomes significantly compared to chemotherapy alone. Full article
(This article belongs to the Special Issue Lipoprotein Nanoparticles for Diagnosis and Therapy)
►▼ Show Figures

Graphical abstract

20 pages, 2382 KiB  
Article
Role of Phagocytosis in the Pro-Inflammatory Response in LDL-Induced Foam Cell Formation; a Transcriptome Analysis
by Alexander N. Orekhov, Nikita G. Nikiforov, Vasily N. Sukhorukov, Marina V. Kubekina, Igor A. Sobenin, Wei-Kai Wu, Kathy K. Foxx, Sergey Pintus, Philip Stegmaier, Daria Stelmashenko, Alexander Kel, Alexei N. Gratchev, Alexandra A. Melnichenko, Reinhard Wetzker, Volha I. Summerhill, Ichiro Manabe and Yumiko Oishi
Int. J. Mol. Sci. 2020, 21(3), 817; https://doi.org/10.3390/ijms21030817 - 27 Jan 2020
Cited by 25 | Viewed by 5471
Abstract
Excessive accumulation of lipid inclusions in the arterial wall cells (foam cell formation) caused by modified low-density lipoprotein (LDL) is the earliest and most noticeable manifestation of atherosclerosis. The mechanisms of foam cell formation are not fully understood and can involve altered lipid [...] Read more.
Excessive accumulation of lipid inclusions in the arterial wall cells (foam cell formation) caused by modified low-density lipoprotein (LDL) is the earliest and most noticeable manifestation of atherosclerosis. The mechanisms of foam cell formation are not fully understood and can involve altered lipid uptake, impaired lipid metabolism, or both. Recently, we have identified the top 10 master regulators that were involved in the accumulation of cholesterol in cultured macrophages induced by the incubation with modified LDL. It was found that most of the identified master regulators were related to the regulation of the inflammatory immune response, but not to lipid metabolism. A possible explanation for this unexpected result is a stimulation of the phagocytic activity of macrophages by modified LDL particle associates that have a relatively large size. In the current study, we investigated gene regulation in macrophages using transcriptome analysis to test the hypothesis that the primary event occurring upon the interaction of modified LDL and macrophages is the stimulation of phagocytosis, which subsequently triggers the pro-inflammatory immune response. We identified genes that were up- or downregulated following the exposure of cultured cells to modified LDL or latex beads (inert phagocytosis stimulators). Most of the identified master regulators were involved in the innate immune response, and some of them were encoding major pro-inflammatory proteins. The obtained results indicated that pro-inflammatory response to phagocytosis stimulation precedes the accumulation of intracellular lipids and possibly contributes to the formation of foam cells. In this way, the currently recognized hypothesis that the accumulation of lipids triggers the pro-inflammatory response was not confirmed. Comparative analysis of master regulators revealed similarities in the genetic regulation of the interaction of macrophages with naturally occurring LDL and desialylated LDL. Oxidized and desialylated LDL affected a different spectrum of genes than naturally occurring LDL. These observations suggest that desialylation is the most important modification of LDL occurring in vivo. Thus, modified LDL caused the gene regulation characteristic of the stimulation of phagocytosis. Additionally, the knock-down effect of five master regulators, such as IL15, EIF2AK3, F2RL1, TSPYL2, and ANXA1, on intracellular lipid accumulation was tested. We knocked down these genes in primary macrophages derived from human monocytes. The addition of atherogenic naturally occurring LDL caused a significant accumulation of cholesterol in the control cells. The knock-down of the EIF2AK3 and IL15 genes completely prevented cholesterol accumulation in cultured macrophages. The knock-down of the ANXA1 gene caused a further decrease in cholesterol content in cultured macrophages. At the same time, knock-down of F2RL1 and TSPYL2 did not cause an effect. The results obtained allowed us to explain in which way the inflammatory response and the accumulation of cholesterol are related confirming our hypothesis of atherogenesis development based on the following viewpoints: LDL particles undergo atherogenic modifications that, in turn, accompanied by the formation of self-associates; large LDL associates stimulate phagocytosis; as a result of phagocytosis stimulation, pro-inflammatory molecules are secreted; these molecules cause or at least contribute to the accumulation of intracellular cholesterol. Therefore, it became obvious that the primary event in this sequence is not the accumulation of cholesterol but an inflammatory response. Full article
(This article belongs to the Special Issue Lipoprotein Nanoparticles for Diagnosis and Therapy)
►▼ Show Figures

Graphical abstract

12 pages, 3054 KiB  
Article
Loss of SR-BI Down-Regulates MITF and Suppresses Extracellular Vesicle Release in Human Melanoma
by Katharina Kinslechner, Birgit Schütz, Martina Pistek, Philipp Rapolter, Hans P. Weitzenböck, Harald Hundsberger, Wolfgang Mikulits, Johannes Grillari, Clemens Röhrl, Markus Hengstschläger, Herbert Stangl and Mario Mikula
Int. J. Mol. Sci. 2019, 20(5), 1063; https://doi.org/10.3390/ijms20051063 - 1 Mar 2019
Cited by 11 | Viewed by 4273
Abstract
Melanoma is a skin tumor with a high tendency for metastasis and thus is one of the deadliest cancers worldwide. Here, we investigated the expression of the scavenger receptor class B type 1 (SR-BI), a high-density lipoprotein (HDL) receptor, and tested for its [...] Read more.
Melanoma is a skin tumor with a high tendency for metastasis and thus is one of the deadliest cancers worldwide. Here, we investigated the expression of the scavenger receptor class B type 1 (SR-BI), a high-density lipoprotein (HDL) receptor, and tested for its role in melanoma pigmentation as well as extracellular vesicle release. We first analyzed the expression of SR-BI in patient samples and found a strong correlation with MITF expression as well as with the melanin synthesis pathway. Hence, we asked whether SR-BI could also play a role for the secretory pathway in metastatic melanoma cells. Interestingly, gain- and loss-of-function of SR-BI revealed regulation of the proto-oncogene MET. In line, SR-BI knockdown reduced expression of the small GTPase RABB22A, the ESCRT-II protein VPS25, and SNAP25, a member of the SNARE complex. Accordingly, reduced overall extracellular vesicle generation was detected upon loss of SR-BI. In summary, SR-BI expression in human melanoma enhances the formation and transport of extracellular vesicles, thereby contributing to the metastatic phenotype. Therapeutic targeting of SR-BI would not only interfere with cholesterol uptake, but also with the secretory pathway, therefore suppressing a key hallmark of the metastatic program. Full article
(This article belongs to the Special Issue Lipoprotein Nanoparticles for Diagnosis and Therapy)
►▼ Show Figures

Graphical abstract

Review

Jump to: Research

16 pages, 1048 KiB  
Review
Roles of Reconstituted High-Density Lipoprotein Nanoparticles in Cardiovascular Disease: A New Paradigm for Drug Discovery
by Jiansheng Huang, Dongdong Wang, Li-Hao Huang and Hui Huang
Int. J. Mol. Sci. 2020, 21(3), 739; https://doi.org/10.3390/ijms21030739 - 23 Jan 2020
Cited by 33 | Viewed by 5453
Abstract
Epidemiological results revealed that there is an inverse correlation between high-density lipoprotein (HDL) cholesterol levels and risks of atherosclerotic cardiovascular disease (ASCVD). Mounting evidence supports that HDLs are atheroprotective, therefore, many therapeutic approaches have been developed to increase HDL cholesterol (HDL-C) levels. Nevertheless, [...] Read more.
Epidemiological results revealed that there is an inverse correlation between high-density lipoprotein (HDL) cholesterol levels and risks of atherosclerotic cardiovascular disease (ASCVD). Mounting evidence supports that HDLs are atheroprotective, therefore, many therapeutic approaches have been developed to increase HDL cholesterol (HDL-C) levels. Nevertheless, HDL-raising therapies, such as cholesteryl ester transfer protein (CETP) inhibitors, failed to ameliorate cardiovascular outcomes in clinical trials, thereby casting doubt on the treatment of cardiovascular disease (CVD) by increasing HDL-C levels. Therefore, HDL-targeted interventional studies were shifted to increasing the number of HDL particles capable of promoting ATP-binding cassette transporter A1 (ABCA1)-mediated cholesterol efflux. One such approach was the development of reconstituted HDL (rHDL) particles that promote ABCA1-mediated cholesterol efflux from lipid-enriched macrophages. Here, we explore the manipulation of rHDL nanoparticles as a strategy for the treatment of CVD. In addition, we discuss technological capabilities and the challenge of relating preclinical in vivo mice research to clinical studies. Finally, by drawing lessons from developing rHDL nanoparticles, we also incorporate the viabilities and advantages of the development of a molecular imaging probe with HDL nanoparticles when applied to ASCVD, as well as gaps in technology and knowledge required for putting the HDL-targeted therapeutics into full gear. Full article
(This article belongs to the Special Issue Lipoprotein Nanoparticles for Diagnosis and Therapy)
►▼ Show Figures

Graphical abstract

22 pages, 1817 KiB  
Review
Lipoprotein Drug Delivery Vehicles for Cancer: Rationale and Reason
by Jaideep Chaudhary, Joseph Bower and Ian R. Corbin
Int. J. Mol. Sci. 2019, 20(24), 6327; https://doi.org/10.3390/ijms20246327 - 15 Dec 2019
Cited by 25 | Viewed by 8519
Abstract
Lipoproteins are a family of naturally occurring macromolecular complexes consisting amphiphilic apoproteins, phospholipids, and neutral lipids. The physiological role of mammalian plasma lipoproteins is to transport their apolar cargo (primarily cholesterol and triglyceride) to their respective destinations through a highly organized ligand-receptor recognition [...] Read more.
Lipoproteins are a family of naturally occurring macromolecular complexes consisting amphiphilic apoproteins, phospholipids, and neutral lipids. The physiological role of mammalian plasma lipoproteins is to transport their apolar cargo (primarily cholesterol and triglyceride) to their respective destinations through a highly organized ligand-receptor recognition system. Current day synthetic nanoparticle delivery systems attempt to accomplish this task; however, many only manage to achieve limited results. In recent years, many research labs have employed the use of lipoprotein or lipoprotein-like carriers to transport imaging agents or drugs to tumors. The purpose of this review is to highlight the pharmacologic, clinical, and molecular evidence for utilizing lipoprotein-based formulations and discuss their scientific rationale. To accomplish this task, evidence of dynamic drug interactions with circulating plasma lipoproteins are presented. This is followed by epidemiologic and molecular data describing the association between cholesterol and cancer. Full article
(This article belongs to the Special Issue Lipoprotein Nanoparticles for Diagnosis and Therapy)
►▼ Show Figures

Figure 1

14 pages, 659 KiB  
Review
The Atherogenic Role of Circulating Modified Lipids in Atherosclerosis
by Volha I. Summerhill, Andrey V. Grechko, Shaw-Fang Yet, Igor A. Sobenin and Alexander N. Orekhov
Int. J. Mol. Sci. 2019, 20(14), 3561; https://doi.org/10.3390/ijms20143561 - 20 Jul 2019
Cited by 119 | Viewed by 8017
Abstract
Lipid accumulation in the arterial wall is a crucial event in the development of atherosclerotic lesions. Circulating low-density lipoprotein (LDL) is the major source of lipids that accumulate in the atherosclerotic plaques. It was discovered that not all LDL is atherogenic. In the [...] Read more.
Lipid accumulation in the arterial wall is a crucial event in the development of atherosclerotic lesions. Circulating low-density lipoprotein (LDL) is the major source of lipids that accumulate in the atherosclerotic plaques. It was discovered that not all LDL is atherogenic. In the blood plasma of atherosclerotic patients, LDL particles are the subject of multiple enzymatic and non-enzymatic modifications that determine their atherogenicity. Desialylation is the primary and the most important atherogenic LDL modification followed by a cascade of other modifications that also increase blood atherogenicity. The enzyme trans-sialidase is responsible for the desialylation of LDL, therefore, its activity plays an important role in atherosclerosis development. Moreover, circulating modified LDL is associated with immune complexes that also have a strong atherogenic potential. Moreover, it was shown that antibodies to modified LDL are also atherogenic. The properties of modified LDL were described, and the strong evidence indicating that it is capable of inducing intracellular accumulation of lipids was presented. The accumulated evidence indicated that the molecular properties of modified LDL, including LDL-containing immune complexes can serve as the prognostic/diagnostic biomarkers and molecular targets for the development of anti-atherosclerotic drugs. Full article
(This article belongs to the Special Issue Lipoprotein Nanoparticles for Diagnosis and Therapy)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-7
Back to TopTop