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Pharmaceutics
Special Issues
ROS-Mediated Nano Drug Delivery for Antitumor Therapy
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ROS-Mediated Nano Drug Delivery for Antitumor Therapy

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Nanomedicine and Nanotechnology".

Deadline for manuscript submissions: 28 February 2025 | Viewed by 708

Special Issue Editors

Dr. Yanjuan Huang

E-Mail Website
Guest Editor
School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China
Interests: antitumor nanomedicine; ROS-mediated tumor oxidation therapy; ROS-responsive prodrug/nanodrug delivery; ROS-mediated immunotherapy; ROS-mediated combination therapy; advanced targeted drug delivery system with nanomedicine or macrophage; ROS-responsive hydrogel
Dr. Xiaoyu Xu

E-Mail Website
Guest Editor
Department of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China
Interests: advanced drug delivery systems with bioactive materials; ROS-mediated combination therapy; nanomedicine; antitumor immunotherapy

Special Issue Information

Dear Colleagues,

We are pleased to invite you to submit original research papers and reviews in the field of ROS-mediated antitumor nanomedicine. ROS are a class of chemically reactive small molecules containing oxygen. Compared with normal cells, tumor cells generally have higher concentrations of ROS and are more susceptible to oxidative stress-induced cell death, which makes ROS-based therapies inherently tumor-selective. ROS-mediated tumor oxidation therapy and ROS-responsive drug delivery system are two key components of ROS-mediated therapies. Recently, ROS has emerged as an innovative and unique treatment mode as it can not only directly kill tumor cells but also induce immunogenic cell death (ICD) to activate the body’s immune responses. In addition, it can be easily generated and modulated by means of photodynamic therapy (PDT), sonodynamic therapy (SDT), chemodynamic therapy (CDT), radiodynamic therapy (RDT), microdynamic therapy (MDT), and electrodynamic therapy (EDT).

This Special Issue aims at gathering recent advancements in this field, encompassing topics such as PDT, SDT, CDT, RDT, MDT, EDT, ROS-mediated immunotherapy, ROS-responsive drug delivery system for anti-tumor nanomedicine, and other related topics.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following: ROS-mediated tumor oxidation therapy/combination therapy, ROS-responsive anti-tumor drug delivery system, ROS-mediated tumor immunotherapy, and other related areas.

We look forward to receiving your contributions.

Dr. Yanjuan Huang
Dr. Xiaoyu 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. 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

  • antitumor therapy
  • reactive oxygen species (ROS)
  • ROS-mediated biomedical nanotechnology
  • ROS-responsive nano drug delivery
  • ROS-mediated immunotherapy
  • ROS-mediated combination therapy
  • oxidation therapy
  • photodynamic therapy (PDT)
  • sonodynamic therapy (SDT)
  • chemodynamic therapy (CDT)
  • radiodynamic therapy (RDT)
  • microdynamic therapy (MDT)
  • electrodynamic therapy (EDT)

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

Published Papers (1 paper)

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Research

16 pages, 6034 KiB  
Article
Precisely Tailoring Molecular Structure of Doxorubicin Prodrugs to Enable Stable Nanoassembly, Rapid Activation, and Potent Antitumor Effect
by Chengcheng Feng, Yuting Wang, Jiaxu Xu, Yanzi Zheng, Wenhu Zhou, Yuequan Wang and Cong Luo
Pharmaceutics 2024, 16(12), 1582; https://doi.org/10.3390/pharmaceutics16121582 - 11 Dec 2024
Viewed by 445
Abstract
Background: Achieving a balance between stable drug loading/delivery and on-demand drug activation/release at the target sites remains a significant challenge for nanomedicines. Carrier-free prodrug nanoassemblies, which rely on the design of prodrug molecules, offer a promising strategy to optimize both drug delivery efficiency [...] Read more.
Background: Achieving a balance between stable drug loading/delivery and on-demand drug activation/release at the target sites remains a significant challenge for nanomedicines. Carrier-free prodrug nanoassemblies, which rely on the design of prodrug molecules, offer a promising strategy to optimize both drug delivery efficiency and controlled drug release profiles. Methods: A library of doxorubicin (DOX) prodrugs was created by linking DOX to fatty alcohols of varying chain lengths via a tumor-responsive disulfide bond. In vitro studies assessed the stability and drug release kinetics of the nanoassemblies. In vivo studies evaluated their drug delivery efficiency, tumor accumulation, and antitumor activity in mouse models. Results: In vitro results demonstrated that longer fatty alcohol chains improved the stability of the nanoassemblies but slowed down the disassembly and drug release process. DSSC16 NAs (hexadecanol-modified DOX prodrug) significantly prolonged blood circulation time and enhanced tumor accumulation, with AUC values 14.2-fold higher than DiR Sol. In 4T1 tumor-bearing mouse models, DSSC16 NAs exhibited notably stronger antitumor activity, resulting in a final mean tumor volume of 144.39 ± 36.77 mm3, significantly smaller than that of all other groups (p < 0.05 by ANOVA at a 95% confidence interval). Conclusions: These findings underscore the critical role of prodrug molecule design in the development of effective prodrug nanoassemblies. The balance between stability and drug release is pivotal for optimizing drug delivery and maximizing therapeutic efficacy. Full article
(This article belongs to the Special Issue ROS-Mediated Nano Drug Delivery for Antitumor Therapy)
►▼ Show Figures

Figure 1

Figure 1
<p>Preparation and characterization of fatty alcohol-DOX prodrug nanoassemblies. (<b>A</b>) Schematic diagram of prodrug nanoassemblies; Photographs and particle size distribution profiles of (<b>B</b>) DSSC8 NAs, (<b>C</b>) DSSC12 NAs, (<b>D</b>) DSSC16 Nas, and (<b>E</b>) DSSC20 NAs; (<b>F</b>) Molecular docking simulation of prodrug nanoassemblies pink and light blue: Carbon atom, red: Oxygen atom, yellow: Sulfur atom, blue: Nitrogen atom; (<b>G</b>) The size change curves of prodrug nanoassemblies (n = 3); Colloidal stability of prodrug nanoassemblies incubated in (<b>H</b>) PBS (pH 7.4) and (<b>I</b>) PBS (pH 7.4) containing 10% FBS (n = 3); and (<b>J</b>) Long-term colloidal stability of prodrug nanoassemblies at 4 °C (n = 3).</p> Full article ">Figure 2
<p>DTT-triggered prodrug activation and mechanism. The in vitro drug release of the active intermediate (DOX-SH) at 5 mM DTT from DSSC8 NAs (<b>A</b>), DSSC12 NAs (<b>B</b>), DSSC16 NAs (<b>C</b>), and DSSC20 NAs (<b>D</b>) (n = 3). The proportion of remaining prodrug in 1 mM (<b>E</b>) and 0 mM (<b>F</b>) (n = 3); (<b>G</b>) DTT-triggered drug release mechanism of DSSC8 NAs, DSSC12 NAs, DSSC16 Nas, and DSSC20 NAs.</p> Full article ">Figure 3
<p>Cellular uptake and MTT assay. (<b>A</b>) CLSM images of 4T1 cells incubated with C6 Sol or C6-labeled prodrug-nanoassemblies for 0.5 h and 2 h (scale bar = 10 μm); Flow cytometric analyses of 4T1 cells incubated with C6 sol or C6-labeled prodrug-nanoassemblies for (<b>B</b>) 0.5 and (<b>C</b>) 2 h (n = 3) * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001, n.s. no significant; Cell viability after treated with various concentrations of DOX Sol and prodrug nanoassemblies for 48 h in (<b>D</b>) 4T1 cells, (<b>E</b>) RM-1 cells, and (<b>F</b>) CT26 cells (n = 3).</p> Full article ">Figure 4
<p>Pharmacokinetic and in vivo biodistribution. (<b>A</b>) Pharmacokinetic profiles of DiR Sol and DiR-labeled prodrug-nanoassemblies following a single intravenous administration of 2 mg/kg (DiR equivalent) (n = 5); (<b>B</b>) Living images of 4T1 tumor-bearing BALB/c mice treated with DiR Sol and DiR-labeled prodrug-nanoassemblies at a DiR equivalent dose of 1.5 mg/kg; (<b>C</b>) Quantitative analysis of excised tissues treated with various formulations at the time when tumor accumulation was brightest (n = 3). ** <span class="html-italic">p</span> &lt; 0.01.</p> Full article ">Figure 5
<p>In vivo antitumor efficacy of prodrug nanoassemblies. (<b>A</b>) Treatment schedule; (<b>B</b>) Digital images of excised tumors from 4T1 tumor-bearing BALB/c mice following various treatments (× represents the death of the mice); (<b>C</b>) Tumor growth curves post-treatment; (<b>D</b>) Tumor burden following different treatments; (<b>E</b>) Hepatic and renal function assessments post-treatment, including alanine aminotransferase (ALT, U/L), aspartate aminotransferase (AST, U/L), creatinine (CREA, μmol/L), and blood urea nitrogen (BUN, mg/dL) (n = 3). (<b>F</b>) Body weight changes during treatment; (<b>G</b>) H&amp;E and TUNEL staining of tumor tissues after treatment (Scale bar = 100 μm). * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01.</p> Full article ">Scheme 1
<p>Precisely Programming Prodrug Molecular Structure to Enable Stable Nanoassembly and Rapid Activation.</p> Full article ">
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: Precisely Tailoring Molecular Structure of Doxorubicin Prodrugs to Enable Stable Nanoassembly, Rapid Activation, and Potent Antitumor Effect
Authors: Chengcheng Feng; Yuting Wang; Jiaxu Xu; Yanzi Zheng; Wenhu Zhou; Shenwu Zhang; Jin Sun; Zhonggui He; Yuequan Wang; Cong Luo
Affiliation: Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, P. R. China
Abstract: Achieving a balance between stable drug loading/delivery and on-demand drug activation/release at target sites remains a challenge for nanomedicines. In particular, carrier-free prodrug nanoassemblies depend on the design of prodrug molecules to optimize both delivery efficiency and drug activation profiles. Herein, a library of doxorubicin (DOX) prodrugs is obtained by linking DOX to fatty alcohols of varying chain lengths through tumor-responsive disulfide bond. In vitro results indicate that longer fatty alcohol chains improve the stability of the nanoassemblies but slow down disassembly and drug activation. Notably, in vivo studies reveal a close correlation between drug delivery efficiency, antitumor activity, and the stability and release characteristics of the prodrug nanoassemblies. The hexadecanol-modified DOX prodrug (DSSC16) achieves a favorable balance between nanoassembly stability and drug activation performance, demonstrating the most potent antitumor activity compared to other prodrug nanoassemblies in 4T1 tumor-bearing mouse models. These findings highlight the importance of prodrug molecule design in the development of effective prodrug nanoassemblies.

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