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Pharmaceutics
Special Issues
Recent Advances in Drug Targeting for Cancer Treatment
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Recent Advances in Drug Targeting for Cancer Treatment

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Targeting and Design".

Deadline for manuscript submissions: closed (20 February 2024) | Viewed by 6855

Special Issue Editor

Dr. Hiep Tuan Tran

E-Mail Website
Guest Editor
Faculty of Pharmacy, Phenikaa University, Yen Nghia, Ha Dong, Hanoi 12116, Vietnam
Interests: oncology; nanotechnology; drug delivery system; targeting therapy

Special Issue Information

Dear Colleagues,

Cancer remains the leading cause of death despite the tremendous effort in the development process of active ingredients and therapeutic approaches and delivery strategies. This hurdle may account for the resistance and metastatic progression due to the lack of specificity of active treatments. The targeting therapy sheds light for a better hope of “cure” in which cell–cell communication, cellular surface, cellular organelle, intrinsic signaling or cellular genetic materials could be on target for a potential treatment. This Special Issue proposes an open forum for updated strategies towards target cancer cells. New molecules, therapies with a low cytotoxicity, high efficacy or delivery systems with high loading capacity, biocompatibility, and tumor specificity could offer cancer patients new opportunities for improving effectiveness and life quality.

We look forward to receiving your contributions.

Dr. Hiep Tuan Tran
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. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). 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

  • oncology
  • nanotechnology
  • gene therapy
  • targeting therapy
  • anticancer drugs
  • drug delivery systems

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Published Papers (3 papers)

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Research

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20 pages, 3297 KiB  
Article
Combination of Betulinic Acid Fragments and Carbonic Anhydrase Inhibitors—A New Drug Targeting Approach
by Matthias Bache, Niels V. Heise, Andreas Thiel, Anne Funtan, Franziska Seifert, Marina Petrenko, Antje Güttler, Sarah Brandt, Thomas Mueller, Dirk Vordermark, Iris Thondorf, René Csuk and Reinhard Paschke
Pharmaceutics 2024, 16(3), 401; https://doi.org/10.3390/pharmaceutics16030401 - 14 Mar 2024
Viewed by 1525
Abstract
Human carbonic anhydrase IX (hCA IX) is a zinc(II)-dependent metalloenzyme that plays a critical role in the conversion of carbon dioxide and water to protons and bicarbonate. It is a membrane-bound protein with an extracellular catalytic center that is predominantly overexpressed in solid [...] Read more.
Human carbonic anhydrase IX (hCA IX) is a zinc(II)-dependent metalloenzyme that plays a critical role in the conversion of carbon dioxide and water to protons and bicarbonate. It is a membrane-bound protein with an extracellular catalytic center that is predominantly overexpressed in solid hypoxic tumors. Sulfamates and sulfonamides, for example acetazolamide (AZA), have been used to inhibit hCA IX in order to improve the response to solid hypoxic tumors. In the present study, we propose a new drug targeting approach by attaching the natural cytotoxic substances betulin and betulinic acid (BA) via a linker to sulfonamides. The conjugate was designed with different spacer lengths to accumulate at the target site of hCA IX. Computational and cell biological studies suggest that the length of the linker may influence hCA IX inhibition. Cytotoxicity tests of the newly synthesized bifunctional conjugates 3, 5, and 9 show effective cytotoxicity in the range of 6.4 and 30.1 µM in 2D and 3D tumor models. The hCA IX inhibition constants of this conjugates, measured using an in vitro enzyme assay with p-nitrophenyl acetate, were determined in a low µM-range, and all compounds reveal a significant inhibition of hypoxia-induced CA activity in a cell-based assay using the Wilbur–Anderson method. In addition, the cells respond with G1 increase and apoptosis induction. Overall, the dual strategy to produce cytotoxic tumor therapeutics that inhibit tumor-associated hCA IX was successfully implemented. Full article
(This article belongs to the Special Issue Recent Advances in Drug Targeting for Cancer Treatment)
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Review

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58 pages, 12931 KiB  
Review
Podophyllotoxin: Recent Advances in the Development of Hybridization Strategies to Enhance Its Antitumoral Profile
by Carolina Miranda-Vera, Ángela Patricia Hernández, Pilar García-García, David Díez, Pablo Anselmo García and María Ángeles Castro
Pharmaceutics 2023, 15(12), 2728; https://doi.org/10.3390/pharmaceutics15122728 - 4 Dec 2023
Cited by 6 | Viewed by 2762
Abstract
Podophyllotoxin is a naturally occurring cyclolignan isolated from rhizomes of Podophyllum sp. In the clinic, it is used mainly as an antiviral; however, its antitumor activity is even more interesting. While podophyllotoxin possesses severe side effects that limit its development as an anticancer [...] Read more.
Podophyllotoxin is a naturally occurring cyclolignan isolated from rhizomes of Podophyllum sp. In the clinic, it is used mainly as an antiviral; however, its antitumor activity is even more interesting. While podophyllotoxin possesses severe side effects that limit its development as an anticancer agent, nevertheless, it has become a good lead compound for the synthesis of derivatives with fewer side effects and better selectivity. Several examples, such as etoposide, highlight the potential of this natural product for chemomodulation in the search for new antitumor agents. This review focuses on the recent chemical modifications (2017–mid-2023) of the podophyllotoxin skeleton performed mainly at the C-ring (but also at the lactone D-ring and at the trimethoxyphenyl E-ring) together with their biological properties. Special emphasis is placed on hybrids or conjugates with other natural products (either primary or secondary metabolites) and other molecules (heterocycles, benzoheterocycles, synthetic drugs, and other moieties) that contribute to improved podophyllotoxin bioactivity. In fact, hybridization has been a good strategy to design podophyllotoxin derivatives with enhanced bioactivity. The way in which the two components are joined (directly or through spacers) was also considered for the organization of this review. This comprehensive perspective is presented with the aim of guiding the medicinal chemistry community in the design of new podophyllotoxin-based drugs with improved anticancer properties. Full article
(This article belongs to the Special Issue Recent Advances in Drug Targeting for Cancer Treatment)
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19 pages, 1765 KiB  
Review
Targeting DNA Damage Repair and Immune Checkpoint Proteins for Optimizing the Treatment of Endometrial Cancer
by Xing Bian, Chuanbo Sun, Jin Cheng and Bo Hong
Pharmaceutics 2023, 15(9), 2241; https://doi.org/10.3390/pharmaceutics15092241 - 30 Aug 2023
Cited by 1 | Viewed by 1982
Abstract
The dependence of cancer cells on the DNA damage response (DDR) pathway for the repair of endogenous- or exogenous-factor-induced DNA damage has been extensively studied in various cancer types, including endometrial cancer (EC). Targeting one or more DNA damage repair protein with small [...] Read more.
The dependence of cancer cells on the DNA damage response (DDR) pathway for the repair of endogenous- or exogenous-factor-induced DNA damage has been extensively studied in various cancer types, including endometrial cancer (EC). Targeting one or more DNA damage repair protein with small molecules has shown encouraging treatment efficacy in preclinical and clinical models. However, the genes coding for DDR factors are rarely mutated in EC, limiting the utility of DDR inhibitors in this disease. In the current review, we recapitulate the functional role of the DNA repair system in the development and progression of cancer. Importantly, we discuss strategies that target DDR proteins, including PARP, CHK1 and WEE1, as monotherapies or in combination with cytotoxic agents in the treatment of EC and highlight the compounds currently being evaluated for their efficacy in EC in clinic. Recent studies indicate that the application of DNA damage agents in cancer cells leads to the activation of innate and adaptive immune responses; targeting immune checkpoint proteins could overcome the immune suppressive environment in tumors. We further summarize recently revolutionized immunotherapies that have been completed or are now being evaluated for their efficacy in advanced EC and propose future directions for the development of DDR-based cancer therapeutics in the treatment of EC. Full article
(This article belongs to the Special Issue Recent Advances in Drug Targeting for Cancer Treatment)
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