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

Deadline for manuscript submissions: closed (18 August 2023) | Viewed by 32565

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Special Issue Editors

Dr. Nagavendra Kommineni

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Guest Editor

Center for Biomedical Research (CBR) Population Council, The Rockefeller University, New York, NY 10065, USA
Interests: nanomedicine; drug delivery; cancer, HIV and contraception; pharmaceutical product development; nanotoxicology; pharmacokinetics; topical and transdermal delivery; sterile injectable formulations; targeted delivery for cancer

Dr. Veera Ganesh Yerra

E-Mail Website
Guest Editor

Department of Pharmacology and Systems Physiology, Cardiovascular Research Centre, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267, USA
Interests: diabetic complications; diabetic neuropathy; heart failure; cardiomyopathy; inflammatory diseases; oxidative stress; autopahgy; mitochondrial dysfunction; nanomedicine; targeted drug delivery for diabetic and cardiovascular complications

Special Issue Information

Dear Colleagues,

Nanomedicine is an emerging platform used to tackle different diseases in the world. The emergence of nanomedicine has improved patient life expectancy and eradicated drug-resistant diseases. The advantages of a nanomedicine platform includes improvements in the pharmacokinetics of therapeutic molecules, improving their solubility as well as bioavailability. A nanomedicine platform not only provides new therapies but also improves the targetability of diseases. Several nanomedicines exist in the market, such as liposomes, lipid particles, dendrimers, polymeric nanoparticles, protein nanoparticles, etc. Nanocarriers help in delivering small molecules, proteins and peptides, and genes to the target site of action. Some COVID-19 vaccines also fall under the nanomedicine platform for delivering target-specific miRNA. Several research communities focus on therapeutic strategies using nanomedicine to manage cancer, diabetes, viral infections, HIV, HSV, and other rare diseases. The limitations of nanomedicine platforms such as the toxicity of some nanomedicines as well as the long-term complications need to be thoroughly investigated. Recent advances in this area of research have shown the potential application of nanodelivery systems in delivering a variety of biopharmaceuticals. This Special Issue is focused on the recent advances, methods, and approaches in preparing nanocarriers and their characterization techniques.

In this Special Issue of IJMS, the focus will be on nanomedicine platforms for cancer, viral infections, diabetes, HIV, and other rare diseases with new treatment options.

Suitable topics include, but are not limited to, the following:

Nanomedicine for cancer therapy;
Nanomedicine platform for viral infections;
Nanomedicine strategies for vaccine delivery;
Nanomedicine for immune engineering;
Pros and cons of nanomedicine and its toxicology;
Nanomedicine for topical and transdermal delivery;
Nanomedicine for oral delivery;
Nanomedicine for parenteral delivery;
Nanomedicine for lung infections;
Nanomedicine for ocular diseases;
Nanomedicine for diabetes and its complications;
Nanomedicine for inflammatory diseases;
Nanotherapeutic approaches targeting mitochondria.

Dr. Nagavendra Kommineni
Dr. Veera Ganesh Yerra
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

nanomedicine
nanotoxicology
cancer
viral infections
gene delivery
vaccines
drug delivery

Published Papers (6 papers)

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Research

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13 pages, 2787 KiB

Open AccessArticle

Pegylated Gold Nanoparticles Conjugated with siRNA: Complexes Formation and Cytotoxicity

by Elżbieta Okła, Piotr Białecki, Marta Kędzierska, Elżbieta Pędziwiatr-Werbicka, Katarzyna Miłowska, Samuel Takvor, Rafael Gómez, Francisco Javier de la Mata, Maria Bryszewska and Maksim Ionov

Int. J. Mol. Sci. 2023, 24(7), 6638; https://doi.org/10.3390/ijms24076638 - 02 Apr 2023

Cited by 1 | Viewed by 1691

Abstract

Drug delivery systems such as dendrimers, liposomes, polymers or gold/silver nanoparticles could be used to advance modern medicine. One significant pharmacological problem is crossing biological barriers by commonly used drugs, e.g., in the treatment of neurodegenerative diseases, which have a problem of the blood-brain barrier (BBB) restricting drug delivery. Numerous studies have been conducted to find appropriate drug carriers that are safe, biocompatible and efficient. In this work, we evaluate pegylated gold nanoparticles AuNP14a and AuNP14b after their conjugation with therapeutic siRNA directed against APOE4. This genetic risk factor remains the strongest predictor for late-onset Alzheimer’s disease. The study aimed to assess the biophysical properties of AuNPs/siAPOE complexes and to check their biological safety on healthy cells using human brain endothelial cells (HBEC-5i). Techniques such as fluorescence polarization, circular dichroism, dynamic light scattering, ζ-potential measurements and gel retardation assay showed that AuNPs form stable complexes with siRNA. Subsequently, cytotoxicity assays proved the biological safety of formed conjugates. Obtained results enabled us to find effective concentrations of AuNPs when complexes are formed and non-toxic for healthy cells. One of the studied nanoparticles, AuNP14b complexed with siRNA, displayed lower cytotoxicity (MTT assay, cells viability −74.8 ± 3.1%) than free nanoparticles (44.7 ± 3.6%). This may be promising for further investigations in nucleic acid delivery and could have practical use in treating neurodegenerative diseases. Full article

(This article belongs to the Special Issue Latest Advances in Nanomedicine Strategies for Different Diseases)

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18 pages, 6871 KiB

Open AccessArticle

Evaluation of Anticancer Activity of Zhubech, a New 5-FU Analog Liposomal Formulation, against Pancreatic Cancer

by Nkafu Bechem Ndemazie, Raviteja Bulusu, Xue You Zhu, Esther Kesewaah Frimpong, Andriana Inkoom, Joy Okoro, Dexter Ebesoh, Sherise Rogers, Bo Han and Edward Agyare

Int. J. Mol. Sci. 2023, 24(5), 4288; https://doi.org/10.3390/ijms24054288 - 21 Feb 2023

Cited by 3 | Viewed by 2356

Abstract

Pancreatic cancer is projected to be the second leading cause of cancer-related death by 2030 in the US. The benefits of the most common systemic therapy for various pancreatic cancers have been masked by high drug toxicities, adverse reactions, and resistance. The use of nanocarriers such as liposomes to overcome these unwanted effects has become very popular. This study aims to formulate 1,3-bistertrahydrofuran-2yl-5FU (MFU)-loaded liposomal nanoparticles (Zhubech) and to evaluate itsstability, release kinetics, in vitro and in vivo anticancer activities, and biodistribution in different tissues. Particle size and zeta potential were determined using a particle size analyzer, while cellular uptake of rhodamine-entrapped liposomal nanoparticles (Rho-LnPs) was determined by confocal microscopy. Gadolinium hexanoate (Gd-Hex) was synthesized and entrapped into the liposomal nanoparticle (LnP) (Gd-Hex-LnP), as a model contrast agent, to evaluate gadolinium biodistribution and accumulation by LnPs in vivo using inductively coupled plasma mass spectrometry (ICP-MS). The mean hydrodynamic diameters of blank LnPs and Zhubech were 90.0 ± 0.65 nm and 124.9 ± 3.2 nm, respectively. The hydrodynamic diameter of Zhubech was found to be highly stable at 4 °C and 25 °C for 30 days in solution. In vitro drug release of MFU from Zhubech formulation exhibited the Higuchi model (R² value = 0.95). Both Miapaca-2 and Panc-1 treated with Zhubech showed reduced viability, two- or four-fold lower than that of MFU-treated cells in 3D spheroid (IC_50Zhubech = 3.4 ± 1.0 μM vs. IC_50MFU = 6.8 ± 1.1 μM) and organoid (IC_50Zhubech = 9.8 ± 1.4 μM vs. IC_50MFU = 42.3 ± 1.0 μM) culture models. Confocal imaging confirmed a high uptake of rhodamine-entrapped LnP by Panc-1 cells in a time-dependent manner. Tumor-efficacy studies in a PDX bearing mouse model revealed a more than 9-fold decrease in mean tumor volumes in Zhubech-treated (108 ± 13.5 mm³) compared to 5-FU-treated (1107 ± 116.2 mm³) animals, respectively. This study demonstrates that Zhubech may be a potential candidate for delivering drugs for pancreatic cancer treatment. Full article

(This article belongs to the Special Issue Latest Advances in Nanomedicine Strategies for Different Diseases)

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29 pages, 12951 KiB

Open AccessArticle

Supermagnetic Human Serum Albumin (HSA) Nanoparticles and PLGA-Based Doxorubicin Nanoformulation: A Duet for Selective Nanotherapy

by Julia Malinovskaya, Rawan Salami, Marat Valikhov, Veronika Vadekhina, Aleksey Semyonkin, Alevtina Semkina, Maxim Abakumov, Yifat Harel, Esthy Levy, Tzuriel Levin, Rachel Persky, Vladimir Chekhonin, Jean-Paul Lellouche, Pavel Melnikov and Svetlana Gelperina

Int. J. Mol. Sci. 2023, 24(1), 627; https://doi.org/10.3390/ijms24010627 - 30 Dec 2022

Cited by 5 | Viewed by 2113

Abstract

Predicting the ability of nanoparticles (NP) to access the tumor is key to the success of chemotherapy using nanotherapeutics. In the present study, the ability of the dual NP-based theranostic system to accumulate in the tumor was evaluated in vivo using intravital microscopy (IVM) and MRI. The system consisted of model therapeutic doxorubicin-loaded poly(lactide-co-glycolide) NP (Dox-PLGA NP) and novel hybrid Ce^3/4+-doped maghemite NP encapsulated within the HSA matrix (hMNP) as a supermagnetic MRI contrasting agent. Both NP types had similar sizes of ~100 nm and negative surface potentials. The level of the hMNP and PLGA NP co-distribution in the same regions of interest (ROI, ~2500 µm²) was assessed by IVM in mice bearing the 4T1-mScarlet murine mammary carcinoma at different intervals between the NP injections. In all cases, both NP types penetrated into the same tumoral/peritumoral regions by neutrophil-assisted extravasation through vascular micro- and macroleakages. The maximum tumor contrasting in MRI scans was obtained 5 h after hMNP injection/1 h after PLGA NP injection; the co-distribution level at this time reached 78%. Together with high contrasting properties of the hMNP, these data indicate that the hMNP and PLGA NPs are suitable theranostic companions. Thus, analysis of the co-distribution level appears to be a useful tool for evaluation of the dual nanoparticle theranostics, whereas assessment of the leakage areas helps to reveal the tumors potentially responsive to nanotherapeutics. Full article

(This article belongs to the Special Issue Latest Advances in Nanomedicine Strategies for Different Diseases)

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13 pages, 3209 KiB

Open AccessArticle

Synergetic Enhancement of Tumor Double-Targeted MRI Nano-Probe

by Nikita Yabbarov, Elena Nikolskaya, Maria Sokol, Mariia Mollaeva, Margarita Chirkina, Irina Seregina, Mikhail Gulyaev, Yury Pirogov and Rem Petrov

Int. J. Mol. Sci. 2022, 23(6), 3119; https://doi.org/10.3390/ijms23063119 - 14 Mar 2022

Cited by 3 | Viewed by 2398

Abstract

The conventional targeted delivery of chemotherapeutic and diagnostic agents utilizing nanocarriers is a promising approach for cancer theranostics. Unfortunately, this approach often faces hindered tumor access that decreases the therapeutic index and limits the further clinical translation of a developing drug. Here, we demonstrated a strategy of simultaneously double-targeting the drug to two distinct cites of tumor tissue: the tumor endothelium and cell surface receptors. We used fourth-generation polyamideamine dendrimers modified with a chelated Gd and functionalized with selectin ligand and alpha-fetoprotein receptor-binding peptide. According to the proposed strategy, IELLQAR peptide promotes the conjugate recruitment to the tumor inflammatory microenvironment and enhances extravasation through the interaction of nanodevice with P- and E-selectins expressed by endothelial cells. The second target moiety—alpha-fetoprotein receptor-binding peptide—enhances drug internalization into cancer cells and the intratumoral retention of the conjugate. The final conjugate contained 18 chelated Gd ions per dendrimer, characterized with a 32 nm size and a negative surface charge of around 18 mV. In vitro contrasting properties were comparable with commercially available Gd-chelate: r1 relaxivity was 3.39 for Magnevist and 3.11 for conjugate; r2 relaxivity was 5.12 for Magnevist and 4.81 for conjugate. By utilizing this dual targeting strategy, we demonstrated the increment of intratumoral accumulation, and a remarkable enhancement of antitumor effect, resulting in high-level synergy compared to monotargeted conjugates. In summary, the proposed strategy utilizing tumor tissue double-targeting may contribute to an enhancement in drug and diagnostic accumulation in aggressive tumors. Full article

(This article belongs to the Special Issue Latest Advances in Nanomedicine Strategies for Different Diseases)

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Review

Jump to: Research

36 pages, 1825 KiB

Open AccessReview

A Comprehensive Review of mRNA Vaccines

by Vrinda Gote, Pradeep Kumar Bolla, Nagavendra Kommineni, Arun Butreddy, Pavan Kumar Nukala, Sushesh Srivatsa Palakurthi and Wahid Khan

Int. J. Mol. Sci. 2023, 24(3), 2700; https://doi.org/10.3390/ijms24032700 - 31 Jan 2023

Cited by 42 | Viewed by 19508

Abstract

mRNA vaccines have been demonstrated as a powerful alternative to traditional conventional vaccines because of their high potency, safety and efficacy, capacity for rapid clinical development, and potential for rapid, low-cost manufacturing. These vaccines have progressed from being a mere curiosity to emerging as COVID-19 pandemic vaccine front-runners. The advancements in the field of nanotechnology for developing delivery vehicles for mRNA vaccines are highly significant. In this review we have summarized each and every aspect of the mRNA vaccine. The article describes the mRNA structure, its pharmacological function of immunity induction, lipid nanoparticles (LNPs), and the upstream, downstream, and formulation process of mRNA vaccine manufacturing. Additionally, mRNA vaccines in clinical trials are also described. A deep dive into the future perspectives of mRNA vaccines, such as its freeze-drying, delivery systems, and LNPs targeting antigen-presenting cells and dendritic cells, are also summarized. Full article

(This article belongs to the Special Issue Latest Advances in Nanomedicine Strategies for Different Diseases)

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25 pages, 2877 KiB

Open AccessReview

An Overview of the Importance of Transition-Metal Nanoparticles in Cancer Research

by Olga Klaudia Szewczyk, Piotr Roszczenko, Robert Czarnomysy, Anna Bielawska and Krzysztof Bielawski

Int. J. Mol. Sci. 2022, 23(12), 6688; https://doi.org/10.3390/ijms23126688 - 15 Jun 2022

Cited by 16 | Viewed by 2681

Abstract

Several authorities have implied that nanotechnology has a significant future in the development of advanced cancer therapies. Nanotechnology makes it possible to simultaneously administer drug combinations and engage the immune system to fight cancer. Nanoparticles can locate metastases in different organs and deliver medications to them. Using them allows for the effective reduction of tumors with minimal toxicity to healthy tissue. Transition-metal nanoparticles, through Fenton-type or Haber–Weiss-type reactions, generate reactive oxygen species. Through oxidative stress, the particles induce cell death via different pathways. The main limitation of the particles is their toxicity. Certain factors can control toxicity, such as route of administration, size, aggregation state, surface functionalization, or oxidation state. In this review, we attempt to discuss the effects and toxicity of transition-metal nanoparticles. Full article

(This article belongs to the Special Issue Latest Advances in Nanomedicine Strategies for Different Diseases)

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