Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Nano-Strategies: The Future Medicine for Fighting Cancer Progression and Drug Resistance

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Published Papers

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 (29 February 2020) | Viewed by 33597

Share This Special Issue

Special Issue Editor

Dr. Giovanni Luca Beretta

E-Mail Website
Guest Editor

Molecular Pharmacology Unit, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Via Amadeo 42, 20133 Milan, Italy
Interests: cancer research; cancer chemotherapy; molecular biology; cell biology; pharmacology; nanomedicine; drug discovery
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The administration of conventional antitumor therapy is the first choice in clinical practice for patients suffering from disseminated tumors. Unfortunately, the development of drug resistance and systemic toxicity often require the suspension of treatment and lead to tumor progression and patients’ deaths. Among the several strategies considered to counteract drug resistance, the encapsulation of the drugs into nanovectors appears very promising. Importantly, their capability demonstrated in protecting cargo makes nanodevices useful for the delivery of therapeutic nucleic acids, a field of research that has increased significantly in recent years. Despite numerous studies that have proved the efficacy of nanosystems in (i) carrying a large therapeutics “payload”; (ii) accommodating multiple drug molecules that simultaneously enable combinatorial cancer therapy and bypass well-known drug resistance mechanisms; and (iii) targeting specific cells/tissues through the multivalent targeting ligands, which yield high affinity and specificity, only a limited number of nanodevices have attained clinical success (e.g., Doxil and Abraxane). These features imply that additional efforts are required before nanomedicine supplants conventional drug delivery administration. In this Special Issue, we welcome contributions, reviews, and original articles focused on all the aspects embraced by nanostrategies and adopted for combating cancer progression and drug resistance.

Dr. Giovanni L. Beretta
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. 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

Cancer
Antitumor drugs
Nanomedicine
Tumor progression
Metastasis
Drug resistance
Biomarkers
Drug delivery
Pharmacology

Published Papers (7 papers)

Download All Papers

Research

Jump to: Review

14 pages, 1563 KiB

Open AccessArticle

In Vitro Biophysical and Biological Characterization of Lipid Nanoparticles Co-Encapsulating Oncosuppressors miR-199b-5p and miR-204-5p as Potentiators of Target Therapy in Metastatic Melanoma

by Luigi Fattore, Virginia Campani, Ciro Francesco Ruggiero, Valentina Salvati, Domenico Liguoro, Lorena Scotti, Gerardo Botti, Paolo Antonio Ascierto, Rita Mancini, Giuseppe De Rosa and Gennaro Ciliberto

Int. J. Mol. Sci. 2020, 21(6), 1930; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21061930 - 12 Mar 2020

Cited by 16 | Viewed by 3452

Abstract

Uncontrolled MAPK signaling is the main oncogenic driver in metastatic melanomas bearing mutations in BRAF kinase. These tumors are currently treated with the combination of BRAF/MEK inhibitors (MAPKi), but this therapy is plagued by drug resistance. In this context we recently discovered that several microRNAs are involved in the development of drug resistance. In particular miR-204-5p and miR-199b-5p were found to function as antagonists of resistance because their enforced overexpression is able to inhibit melanoma cell growth in vitro either alone or in combination with MAPKi. However, the use of miRNAs in therapy is hampered by their rapid degradation in serum and biological fluids, as well as by the poor intracellular uptake. Here, we developed lipid nanoparticles (LNPs) encapsulating miR-204-5p, miR-199b-5p individually or in combination. We obtained LNPs with mean diameters < 200 nm and high miRNA encapsulation efficiency. These formulations were tested in vitro on several melanoma cell lines sensitive to MAPKi or rendered drug resistant. Our results show that LNPs encapsulating combinations of the two oncosuppressor miRNAs are highly efficient in impairing melanoma cell proliferation and viability, affect key signaling pathways involved in melanoma cell survival, and potentiate the efficacy of drugs inhibiting BRAF and MEK. These results warrant further assessment of the anti-tumor efficacy of oncosuppressor miRNAs encapsulating LNPs in in vivo tumor models. Full article

(This article belongs to the Special Issue Nano-Strategies: The Future Medicine for Fighting Cancer Progression and Drug Resistance)

► Show Figures

Figure 1

18 pages, 2368 KiB

Open AccessArticle

Inhibition of FGFR2-Signaling Attenuates a Homology-Mediated DNA Repair in GIST and Sensitizes Them to DNA-Topoisomerase II Inhibitors

by Boichuk Sergei, Dunaev Pavel, Galembikova Aigul, Bikinieva Firyuza, Nurgatina Ilmira, Mustafin Ilshat, Aukhadieva Aida, Kurtasanov Refat, Andriutsa Natalia, Shagimardanova Elena and Gorbunova Vera

Int. J. Mol. Sci. 2020, 21(1), 352; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21010352 - 05 Jan 2020

Cited by 18 | Viewed by 3977

Abstract

Deregulation of receptor tyrosine kinase (RTK)-signaling is frequently observed in many human malignancies, making activated RTKs the promising therapeutic targets. In particular, activated RTK-signaling has a strong impact on tumor resistance to various DNA damaging agents, e.g., ionizing radiation and chemotherapeutic drugs. We showed recently that fibroblast growth factor receptor (FGFR)-signaling might be hyperactivated in imatinib (IM)-resistant gastrointestinal stromal tumors (GIST) and inhibition of this pathway sensitized tumor cells to the low doses of chemotherapeutic agents, such as topoisomerase II inhibitors. Here, we report that inhibition of FGFR-signaling in GISTs attenuates the repair of DNA double-strand breaks (DSBs), which was evidenced by the delay in γ-H2AX decline after doxorubicin (Dox)-induced DNA damage. A single-cell gel electrophoresis (Comet assay) data showed an increase of tail moment in Dox-treated GIST cells cultured in presence of BGJ398, a selective FGFR1-4 inhibitor, thereby revealing the attenuated DNA repair. By utilizing GFP-based reporter constructs to assess the efficiency of DSBs repair via homologous recombination (HR) and non-homologous end-joining (NHEJ), we found for the first time that FGFR inhibition in GISTs attenuated the homology-mediated DNA repair. Of note, FGFR inhibition/depletion did not reduce the number of BrdU and phospho-RPA foci in Dox-treated cells, suggesting that inhibition of FGFR-signaling has no impact on the processing of DSBs. In contrast, the number of Dox-induced Rad51 foci were decreased when FGFR2-mediated signaling was interrupted/inhibited by siRNA FGFR2 or BGJ398. Moreover, Rad51 and -H2AX foci were mislocalized in FGFR-inhibited GIST and the amount of Rad51 was substantially decreased in -H2AX-immunoprecipitated complexes, thereby illustrating the defect of Rad51 recombinase loading to the Dox-induced DSBs. Finally, as a result of the impaired homology-mediated DNA repair, the increased numbers of hypodiploid (i.e., apoptotic) cells were observed in FGFR2-inhibited GISTs after Dox treatment. Collectively, our data illustrates for the first time that inhibition of FGF-signaling in IM-resistant GIST interferes with the efficiency of DDR signaling and attenuates the homology-mediated DNA repair, thus providing the molecular mechanism of GIST’s sensitization to DNA damaging agents, e.g., DNA-topoisomerase II inhibitors. Full article

(This article belongs to the Special Issue Nano-Strategies: The Future Medicine for Fighting Cancer Progression and Drug Resistance)

► Show Figures

Figure 1

14 pages, 992 KiB

Open AccessArticle

Encapsulation of Lovastatin in Zein Nanoparticles Exhibits Enhanced Apoptotic Activity in HepG2 Cells

by Nabil A. Alhakamy, Osama A.A. Ahmed, Hibah M. Aldawsari, Mohammad Y. Alfaifi, Basma G. Eid, Ashraf B. Abdel-Naim and Usama A. Fahmy

Int. J. Mol. Sci. 2019, 20(22), 5788; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20225788 - 18 Nov 2019

Cited by 31 | Viewed by 3505

Abstract

Research on statins highlights their potent cytotoxicity against cancer cells and their potential for cancer prevention. The aim of the current study was to examine whether loading lovastatin (LVS) in zein (ZN) nanoparticles (NPs) would potentiate the anti-proliferative effects of LVS and enhance its proliferation-inhibiting activity in HepG2 cells. LVS-ZN NPs were prepared and showed excellent characteristics, with respect to their particle size, zeta potential, diffusion, and entrapment efficiency. In addition, they showed the most potent anti-proliferative activity against HepG2 cells. ZN alone showed an observable anti-proliferative that was significantly higher than that of raw LVS. Furthermore, LVS uptake by HepG2 cells was greatly enhanced by the formulation in ZN. A cell cycle analysis indicated that LVS induced a significant cell accumulation in the G2/M and pre-G phases. In this regard, the LVS–ZN NPs exhibited the highest potency. The accumulation in the pre-G phase indicated an enhanced pro-apoptotic activity of the prepared formula. The cells incubated with the LVS-ZN NPs showed the highest percentage of cells with annexin-V positive staining. In addition, the same incubations showed the highest content of caspase-3 enzyme in comparison to raw LVS or ZN. Thus, the loading of LVS in ZN nanoparticles enhances its anti-proliferative activity against HepG2 cells, which is attributed, at least partly, to the enhanced cellular uptake and the induction of apoptosis. Full article

(This article belongs to the Special Issue Nano-Strategies: The Future Medicine for Fighting Cancer Progression and Drug Resistance)

► Show Figures

Figure 1

13 pages, 3075 KiB

Open AccessArticle

Targeting Pancreatic Cancer Cells with Peptide-Functionalized Polymeric Magnetic Nanoparticles

by Xiuliang Zhu, Nan Lu, Ying Zhou, Shaoyan Xuan, Jiaojiao Zhang, Francesca Giampieri, Yongping Zhang, Fangfang Yang, Risheng Yu, Maurizio Battino and Zuhua Wang

Int. J. Mol. Sci. 2019, 20(12), 2988; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20122988 - 19 Jun 2019

Cited by 11 | Viewed by 3684

Abstract

Pancreatic cancer is a concealed and highly malignant tumor, and its early diagnosis plays an increasingly weighty role during the course of cancer treatment. In this study, we developed a polymeric magnetic resonance imaging (MRI) nanoplatform for MRI contrast agents. To improve tumor-targeting delivery of MRI contrast agents, we employed a pancreatic cancer targeting CKAAKN peptide to prepare a peptide-functionalized amphiphilic hyaluronic acid–vitamin E succinate polymer (CKAAKN–HA–VES) for delivering ultra-small superparamagnetic iron oxide (USPIO), namely, CKAAKN–HA–VES@USPIO. With the modification of the CKAAKN peptide, CKAAKN–HA–VES@USPIO could specifically internalize into CKAAKN-positive BxPC-3 cells. The CKAAKN–HA–VES@USPIO nanoparticles presented a more specific accumulation into pancreatic cancer cells than normal pancreatic cells, and an obvious decrease in signal intensity was observed in CKAAKN-positive BxPC-3 cells, compared with CKAAKN-negative HPDE6-C7 cells and non-targeting HA–VES@USPIO nanoparticles. The results demonstrated that our polymeric MRI nanoplatform could selectively internalize into CKAAKN-positive pancreatic cancer cells by the specific binding of CKAAKN peptide with pancreatic cancer cell membrane receptors, which provided a novel polymeric MRI contrast agent with high specificity for pancreatic cancer diagnosis, and makes it a very promising candidate for magnetic resonance imaging contrast enhancement. Full article

(This article belongs to the Special Issue Nano-Strategies: The Future Medicine for Fighting Cancer Progression and Drug Resistance)

► Show Figures

Figure 1

Review

Jump to: Research

17 pages, 1122 KiB

Open AccessReview

MicroRNAs-Based Nano-Strategies as New Therapeutic Approach in Multiple Myeloma to Overcome Disease Progression and Drug Resistance

by Vanessa Desantis, Ilaria Saltarella, Aurelia Lamanuzzi, Assunta Melaccio, Antonio Giovanni Solimando, Maria Addolorata Mariggiò, Vito Racanelli, Angelo Paradiso, Angelo Vacca and Maria Antonia Frassanito

Int. J. Mol. Sci. 2020, 21(9), 3084; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21093084 - 27 Apr 2020

Cited by 42 | Viewed by 3259

Abstract

MicroRNAs (miRNAs, or miRs) are single-strand short non-coding RNAs with a pivotal role in the regulation of physiological- or disease-associated cellular processes. They bind to target miRs modulating gene expression at post-transcriptional levels. Here, we present an overview of miRs deregulation in the pathogenesis of multiple myeloma (MM), and discuss the potential use of miRs/nanocarriers association in clinic. Since miRs can act as oncogenes or tumor suppressors, strategies based on their inhibition and/or replacement represent the new opportunities in cancer therapy. The miRs delivery systems include liposomes, polymers, and exosomes that increase their physical stability and prevent nuclease degradation. Phase I/II clinical trials support the importance of miRs as an innovative therapeutic approach in nanomedicine to prevent cancer progression and drug resistance. Results in clinical practice are promising. Full article

(This article belongs to the Special Issue Nano-Strategies: The Future Medicine for Fighting Cancer Progression and Drug Resistance)

► Show Figures

Figure 1

21 pages, 1010 KiB

Open AccessReview

Nanoparticles Modified with Cell-Penetrating Peptides: Conjugation Mechanisms, Physicochemical Properties, and Application in Cancer Diagnosis and Therapy

by Isabel Gessner and Ines Neundorf

Int. J. Mol. Sci. 2020, 21(7), 2536; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21072536 - 06 Apr 2020

Cited by 112 | Viewed by 7755

Abstract

Based on their tunable physicochemical properties and the possibility of producing cell-specific platforms through surface modification with functional biomolecules, nanoparticles (NPs) represent highly promising tools for biomedical applications. To improve their potential under physiological conditions and to enhance their cellular uptake, combinations with cell-penetrating peptides (CPPs) represent a valuable strategy. CPPs are often cationic peptide sequences that are able to translocate across biological membranes and to carry attached cargos inside cells and have thus been recognized as versatile tools for drug delivery. Nevertheless, the conjugation of CPP to NP surfaces is dependent on many properties from both individual components, and further insight into this complex interplay is needed to allow for the fabrication of highly stable but functional vectors. Since CPPs per se are nonselective and enter nearly all cells likewise, additional decoration of NPs with homing devices, such as tumor-homing peptides, enables the design of multifunctional platforms for the targeted delivery of chemotherapeutic drugs. In this review, we have updated the recent advances in the field of CPP-NPs, focusing on synthesis strategies, elucidating the influence of different physicochemical properties, as well as their application in cancer research. Full article

(This article belongs to the Special Issue Nano-Strategies: The Future Medicine for Fighting Cancer Progression and Drug Resistance)

► Show Figures

Graphical abstract

15 pages, 1768 KiB

Open AccessReview

siRNA Conjugated Nanoparticles—A Next Generation Strategy to Treat Lung Cancer

by Rasha Itani and Achraf Al Faraj

Int. J. Mol. Sci. 2019, 20(23), 6088; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20236088 - 03 Dec 2019

Cited by 64 | Viewed by 7551

Abstract

Despite major progress in both therapeutic and diagnostic techniques, lung cancer is still considered the leading cause of cancer mortality in the world due to the ineffectiveness of the classical treatments used nowadays. Luckily, the discovery of small interfering RNA (siRNA) planted hope in the hearts of scientists and patients worldwide as a new breakthrough in the world of oncology and a robust tool for finally curing cancer. However, the valuable siRNA must be protected and preserved to ensure the effectiveness of this gene therapy, thus nanoparticles are gaining more attention than previous years as the optimal carriers for this fragile molecule. siRNA-loaded nanoparticles are being extensively investigated to find the appropriate formulation, combination, and delivery route with one objective in mind—successfully overcoming all possible limitations shown in clinical studies and making full use of this novel technique to become the next generation treatment to wipe out many chronic diseases, including cancer. In this review, the benefits of using siRNA and nanoparticles in lung cancer treatment will be globally reviewed before discussing why and how nanoparticles and siRNA can be combined to achieve an efficient treatment of lung cancer for prospective clinical applications. Full article

(This article belongs to the Special Issue Nano-Strategies: The Future Medicine for Fighting Cancer Progression and Drug Resistance)

► Show Figures