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Tumor Targeting Theranostics
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Tumor Targeting Theranostics

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

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 9466

Special Issue Editors

Prof. Dr. Yi Liu

grade E-Mail Website
Guest Editor
1. College of Chemistry and Molecular Science, Wuhan University, Wuhan, China
2. State Key Laboratory of Separation Membranes and Membrane Processes, School of Chemistry, Tiangong University, Tianjin 300387, China
Interests: protein interaction; biophysical chemistry; targeting drugs; nanomaterials
Dr. Ziqiang Xu

E-Mail Website
Guest Editor
Hubei Key Laboratory of Polymer Materials, School of Materials Science & Engineering, Hubei University, Wuhan 430062, China
Interests: nano; tumor targeting therapy

Special Issue Information

Dear Colleagues,

In recent years, the development and application of integrated multifunctional moleculars for theranostics have attracted more and more attention. The design of new chemotherapeutic agents that can specifically target the organelles in cells can help selectively kill cancer cells and improve the efficiency of cancer treatment. Discover new multifunctional anticancer agents, especially with a certain subcellular organelle targeting ability, have great value in practical applications in various fields such as cancer diagnosis and therapy. More importantly, the multifunctional moleculars should have excellent mitochondrial targeting and antitumor ability. The aim of this Special Issue is to collect original and review articles which focus on the recent findings related to the molecular imaging, AIE, PDT, PTT, SDT and drug delivery etc. Pure clinical studies are out of the scope of this Special Issue, however, clinical submissions with biomolecular experiments are welcome.

Prof. Dr. Yi Liu
Dr. Ziqiang Xu
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

  • organic
  • inorganic
  • polymers
  • nanoparticles
  • drug delivery

Published Papers (6 papers)

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Research

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25 pages, 17217 KiB  
Article
Hydroxychloroquine-Loaded Chitosan Nanoparticles Induce Anticancer Activity in A549 Lung Cancer Cells: Design, BSA Binding, Molecular Docking, Mechanistic, and Biological Evaluation
by Fawzia I. Elshami, Hadeer A. Shereef, Ibrahim M. El-Mehasseb, Shaban Y. Shaban and Rudi van Eldik
Int. J. Mol. Sci. 2023, 24(18), 14103; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms241814103 - 14 Sep 2023
Viewed by 1027
Abstract
The current study describes the encapsulation of hydroxychloroquine, widely used in traditional medicine due to its diverse pharmacological and medicinal uses, in chitosan nanoparticles (CNPs). This work aims to combine the HCQ drug with CS NPs to generate a novel nanocomposite with improved [...] Read more.
The current study describes the encapsulation of hydroxychloroquine, widely used in traditional medicine due to its diverse pharmacological and medicinal uses, in chitosan nanoparticles (CNPs). This work aims to combine the HCQ drug with CS NPs to generate a novel nanocomposite with improved characteristics and bioavailability. HCQ@CS NPs are roughly shaped like roadways and have a smooth surface with an average size of 159.3 ± 7.1 nm, a PDI of 0.224 ± 0.101, and a zeta potential of +46.6 ± 0.8 mV. To aid in the development of pharmaceutical systems for use in cancer therapy, the binding mechanism and affinity of the interaction between HCQ and HCQ@CS NPs and BSA were examined using stopped-flow and other spectroscopic approaches, supplemented by molecular docking analysis. HCQ and HCQ@CS NPs binding with BSA is driven by a ground-state complex formation that may be accompanied by a non-radiative energy transfer process, and binding constants indicate that HCQ@CS NPs–BSA was more stable than HCQ–BSA. The stopped-flow analysis demonstrated that, in addition to increasing BSA affinity, the nanoformulation HCQ@CS NPS changes the binding process and may open new routes for interaction. Docking experiments verified the development of the HCQ–BSA complex, with HCQ binding to site I on the BSA structure, primarily with the amino acids, Thr 578, Gln 579, Gln 525, Tyr 400, and Asn 404. Furthermore, the nanoformulation HCQ@CS NPS not only increased cytotoxicity against the A549 lung cancer cell line (IC50 = 28.57 ± 1.72 μg/mL) compared to HCQ (102.21 ± 0.67 μg/mL), but also exhibited higher antibacterial activity against both Gram-positive and Gram-negative bacteria when compared to HCQ and chloramphenicol, which is in agreement with the binding constants. The nanoformulation developed in this study may offer a viable therapy option for A549 lung cancer. Full article
(This article belongs to the Special Issue Tumor Targeting Theranostics)
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12 pages, 4632 KiB  
Article
APE-1/Ref-1 Inhibition Blocks Malignant Pleural Mesothelioma Cell Proliferation and Migration: Crosstalk between Oxidative Stress and Epithelial Mesenchymal Transition (EMT) in Driving Carcinogenesis and Metastasis
by Valeria Ramundo, Giada Zanirato, Maria Luisa Palazzo, Chiara Riganti and Elisabetta Aldieri
Int. J. Mol. Sci. 2023, 24(16), 12570; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms241612570 - 08 Aug 2023
Cited by 1 | Viewed by 1053
Abstract
Malignant pleural mesothelioma (MPM) is an aggressive cancer associated with asbestos exposure. MPM pathogenesis has been related both to oxidative stress, evoked by and in response to asbestos fibers exposure, and epithelial mesenchymal transition (EMT), an event induced by oxidative stress itself and [...] Read more.
Malignant pleural mesothelioma (MPM) is an aggressive cancer associated with asbestos exposure. MPM pathogenesis has been related both to oxidative stress, evoked by and in response to asbestos fibers exposure, and epithelial mesenchymal transition (EMT), an event induced by oxidative stress itself and related to cancer proliferation and metastasis. Asbestos-related primary oxidative damage is counteracted in the lungs by various redox-sensitive factors, often hyperactivated in some cancers. Among these redox-sensitive factors, Apurinic-apyrimidinic endonuclease 1 (APE-1)/Redox effector factor 1 (Ref-1) has been demonstrated to be overexpressed in MPM and lung cancer, but the molecular mechanism has not yet been fully understood. Moreover, asbestos exposure has been associated with induced EMT events, via some EMT transcription factors, such as Twist, Zeb-1 and Snail-1, in possible crosstalk with oxidative stress and inflammation events. To demonstrate this hypothesis, we inhibited/silenced Ref-1 in MPM cells; as a consequence, both EMT (Twist, Zeb-1 and Snail-1) markers and cellular migration/proliferation were significantly inhibited. Taken as a whole, these results show, for the first time, crosstalk between oxidative stress and EMT in MPM carcinogenesis and invasiveness, thus improving the knowledge to better address a preventive and therapeutic approach against this aggressive cancer. Full article
(This article belongs to the Special Issue Tumor Targeting Theranostics)
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18 pages, 21332 KiB  
Article
Mitochondria-Targeting Polymer Micelles in Stepwise Response Releasing Gemcitabine and Destroying the Mitochondria and Nucleus for Combined Antitumor Chemotherapy
by Shanming Zhang, Fen Zheng, Kaige Liu, Shengke Liu, Tonghu Xiao, Yabin Zhu and Long Xu
Int. J. Mol. Sci. 2022, 23(20), 12624; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232012624 - 20 Oct 2022
Cited by 4 | Viewed by 1752
Abstract
Mitochondrial DNA and nuclear DNA are essential genetic material which play an important role in maintaining normal metabolism, survival, and proliferation of cells. Constructing a mitochondria-targeting stimuli-responsive nano-drug delivery system releasing chemotherapeutic agents in a stepwise response manner and destroying mitochondrial DNA and [...] Read more.
Mitochondrial DNA and nuclear DNA are essential genetic material which play an important role in maintaining normal metabolism, survival, and proliferation of cells. Constructing a mitochondria-targeting stimuli-responsive nano-drug delivery system releasing chemotherapeutic agents in a stepwise response manner and destroying mitochondrial DNA and nuclear DNA simultaneously is an effective way to improve the anti-tumor effect of chemotherapeutic agents. In this study, a new mitochondria-targeting pH/ROS dual-responsive block copolymer TPP-PEG2k-b-(BS-AA)n (P1), untargeted pH/ROS dual-responsive copolymer mPEG2k-b-(BS-AA)n (P2), pH single-responsive copolymer (mPEG2k-b-(AH-AA)n (P3), ROS single-responsive copolymer mPEG2k-b-(SA-TG)n (P4), and non-responsive copolymer mPEG-b-PCL (P5) were constructed. pH/ROS-responsive properties were characterized by proton nuclear magnetic resonance (1H NMR) and dynamic light scattering (DLS). Anticancer chemotherapeutic agent gemcitabine (GEM) or fluorescent substance Nile Red (NR) were loaded in the polymer micelles. Results of the mitochondrial colocalization experiment indicate that (5-carboxypentyl)(triphenyl)phosphonium bromide (TPP)-functionalized P1 micelles could be efficiently targeted and located in mitochondria. Results of the cellular uptake experiment showed that pH/ROS dual-responsive GEM-loaded P1 and P2 micelles have faster internalized and entry nucleus rates than single-responsive or non-responsive GEM-loaded micelles. The in vitro release experiment suggests pH/ROS dual-responsive GEM/P1 and GEM/P2 micelles have higher cumulative release than single-responsive GEM/P3 and GEM/P4 micelles. The in vitro cytotoxic experiment shows that the mitochondria-targeted dual-responsive GEM/P1 micelles had the lowest IC50 values, and the cytotoxic effect of dual-responsive GEM/P2 micelles was superior to the single-responsive and non-responsive drug-loaded micelles. Full article
(This article belongs to the Special Issue Tumor Targeting Theranostics)
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14 pages, 6766 KiB  
Article
Intelligent Drug Delivery by Peptide-Based Dual-Function Micelles
by Dong Wan, Yujun Liu, Xinhao Guo, Jianxin Zhang and Jie Pan
Int. J. Mol. Sci. 2022, 23(17), 9698; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23179698 - 26 Aug 2022
Cited by 4 | Viewed by 1678
Abstract
To endow the polymeric prodrug with smart properties through a safe and simple method, matrix metalloproteinase (MMPs) responsive peptide GPLGVRGDG was introduced into the block copolymer to prepare TPGS3350-GPLGVRGDG-DOX&DOX micelles, where TPGS3350 is D-α-tocopheryl polyethylene glycol 3350 succinate. During the [...] Read more.
To endow the polymeric prodrug with smart properties through a safe and simple method, matrix metalloproteinase (MMPs) responsive peptide GPLGVRGDG was introduced into the block copolymer to prepare TPGS3350-GPLGVRGDG-DOX&DOX micelles, where TPGS3350 is D-α-tocopheryl polyethylene glycol 3350 succinate. During the doxorubicin delivery, the cleavage of the peptide chain triggers de-PEGylation, and the remaining VRGDG sequence was retained on the surface of the micelles, which can act as a ligand to facilitate cell uptake. Moreover, the cytotoxicity of TPGS3350-GPLGVRGDG-DOX&DOX micelles against 4T1 cells was significantly improved, compared with TPGS3350-GPLGVRG-DOX&DOX micelles and TPGS3350-DOX&DOX micelles. During in vivo studies, TPGS3350-GPLGVRGDG-DOX&DOX micelles exhibited good anticancer efficacy with long circulation in the body and more efficient accumulation at the tumor site. Therefore, TPGS3350-GPLGVRGDG-DOX&DOX micelles have improved antitumor activity and reduced toxic side effects. This work opens new potential for exploring the strategy of drug delivery in clinical applications. Full article
(This article belongs to the Special Issue Tumor Targeting Theranostics)
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Review

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30 pages, 11061 KiB  
Review
A Comprehensive Review of Inorganic Sonosensitizers for Sonodynamic Therapy
by Peng Chen, Ping Zhang, Navid Hussain Shah, Yanyan Cui and Yaling Wang
Int. J. Mol. Sci. 2023, 24(15), 12001; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms241512001 - 26 Jul 2023
Cited by 4 | Viewed by 1907
Abstract
Sonodynamic therapy (SDT) is an emerging non-invasive cancer treatment method in the field of nanomedicine, which has the advantages of deep penetration, good therapeutic efficacy, and minimal damage to normal tissues. Sonosensitizers play a crucial role in the process of SDT, as their [...] Read more.
Sonodynamic therapy (SDT) is an emerging non-invasive cancer treatment method in the field of nanomedicine, which has the advantages of deep penetration, good therapeutic efficacy, and minimal damage to normal tissues. Sonosensitizers play a crucial role in the process of SDT, as their structure and properties directly determine the treatment outcome. Inorganic sonosensitizers, with their high stability and longer circulation time in the human body, have great potential in SDT. In this review, the possible mechanisms of SDT including the ultrasonic cavitation, reactive oxygen species generation, and activation of immunity are briefly discussed. Then, the latest research progress on inorganic sonosensitizers is systematically summarized. Subsequently, strategies for optimizing treatment efficacy are introduced, including combination therapy and image-guided therapy. The challenges and future prospects of sonodynamic therapy are discussed. It is hoped that this review will provide some guidance for the screening of inorganic sonosensitizers. Full article
(This article belongs to the Special Issue Tumor Targeting Theranostics)
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24 pages, 5146 KiB  
Review
Equilibrium Studies on Pd(II)–Amine Complexes with Bio-Relevant Ligands in Reference to Their Antitumor Activity
by Mohamed M. Shoukry and Rudi van Eldik
Int. J. Mol. Sci. 2023, 24(5), 4843; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24054843 - 02 Mar 2023
Cited by 2 | Viewed by 1503
Abstract
This review article presents an overview of the equilibrium studies on Pd-amine complexes with bio-relevant ligands in reference to their antitumor activity. Pd(II) complexes with amines of different functional groups, were synthesized and characterized in many studies. The complex formation equilibria of Pd(amine) [...] Read more.
This review article presents an overview of the equilibrium studies on Pd-amine complexes with bio-relevant ligands in reference to their antitumor activity. Pd(II) complexes with amines of different functional groups, were synthesized and characterized in many studies. The complex formation equilibria of Pd(amine)2+ complexes with amino acids, peptides, dicarboxylic acids and DNA constituents, were extensively investigated. Such systems may be considered as one of the models for the possible reactions occurring with antitumor drugs in biological systems. The stability of the formed complexes depends on the structural parameters of the amines and the bio-relevant ligands. The evaluated speciation curves can help to provide a pictorial presentation of the reactions in solutions of different pH values. The stability data of complexes with sulfur donor ligands compared with those of DNA constituents, can reveal information regarding the deactivation caused by sulfur donors. The formation equilibria of binuclear complexes of Pd(II) with DNA constituents was investigated to support the biological significance of this class of complexes. Most of the Pd(amine)2+ complexes investigated were studied in a low dielectric constant medium, resembling that of a biological medium. Investigations of the thermodynamic parameters reveal that the formation of the Pd(amine)2+ complex species is exothermic. Full article
(This article belongs to the Special Issue Tumor Targeting Theranostics)
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