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Pharmaceutics
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Nano-Drug Delivery Systems for Targeting the Tumor Microenvironment and Simultaneously...
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Nano-Drug Delivery Systems for Targeting the Tumor Microenvironment and Simultaneously Overcoming Drug Resistance Properties

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

Deadline for manuscript submissions: 20 November 2024 | Viewed by 4992

Special Issue Editors

Dr. Odília Queirós

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Guest Editor
UNIPRO—Oral Pathology and Rehabilitation Research Unit, University Institute of Health Sciences, CESPU, CRL, 4585-116 Gandra, Portugal
Interests: cancer cell metabolism; multidrug resistance in cancer cells; Pgp activity; pH regulators in cancer; new anticancer drugs
Special Issues, Collections and Topics in MDPI journals
Dr. Patrícia M. A. Silva

E-Mail Website
Guest Editor
1. UNIPRO—Oral Pathology and Rehabilitation Research Unit, University Institute of Health Sciences (IUCS-CESPU), 4585-116 Gandra, Portugal
2. Associate Laboratory i4HB—Institute for Health and Bioeconomy, University Institute of Health Sciences—CESPU, 4585-116 Gandra, Portugal
3. UCIBIO—Applied Molecular Biosciences Unit, Translational Toxicology Research Laboratory, University Institute of Health Sciences (1H-TOXRUN, IUCS-CESPU), 4585-116 Gandra, Portugal
Interests: anticancer strategies; targeted therapy; cancer biomarkers; mitosis; apoptosis; drug discovery; bioactive compounds
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cancer is a complex disease and one of the most profound challenges to human health. Although new and innovative therapies have emerged throughout the years, the battle against cancer is often lost, with the treatment becoming ineffective and the disease recurring. One of the major obstacles in this fight is the resistance, innate or acquired, developed by cancer cells against the drugs commonly used in chemotherapy. Multidrug resistance, often abbreviated as MDR, is defined as a phenotype, intrinsic or developed during the treatment, where cells are resistant to multiple drugs with no obvious structural similarities and with different molecular targets. Different mechanisms can be involved in MDR, from intracellular adaptations (e.g., the expression of Pgp) to tumour microenvironment (TME) characteristics.

Endogenous stimulus-responsive nanosystems were developed based on the pathophysiological characteristics of the endogenous tumor microenvironment and have emerged as an effective cancer treatment, playing an increasingly important role in combating cancer drug resistance. These nanodrug delivery systems provide flexible and effective methods to overcome multidrug resistance by promoting cellular uptake, increasing drug accumulation, reducing drug efflux, improving targeted drug delivery, co-administering synergistic drugs, and increasing drugs’ half-life in the circulation, thereby improving the effectiveness of cancer treatment.

In this Special Issue, we aim to collect reviews or original manuscripts covering nanosystems with endogenous stimulus-responsive characteristics to overcome MDR and discussing their antitumor effects in vitro and in vivo.

Dr. Odília Queirós
Dr. Patrícia M. A. Silva
Guest Editors

Manuscript Submission Information

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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

  • cancer therapy
  • multidrug resistance
  • mechanisms of drug resistance
  • tumor microenvironment
  • ABC transporters
  • combined therapy
  • drug delivery

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Published Papers (3 papers)

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Research

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16 pages, 3368 KiB  
Article
An Insight into Perfusion Anisotropy within Solid Murine Lung Cancer Tumors
by Antonio Martino, Rossana Terracciano, Bogdan Milićević, Miljan Milošević, Vladimir Simić, Blake C. Fallon, Yareli Carcamo-Bahena, Amber Lee R. Royal, Aileen A. Carcamo-Bahena, Edward Brian Butler, Richard C. Willson, Miloš Kojić and Carly S. Filgueira
Pharmaceutics 2024, 16(8), 1009; https://doi.org/10.3390/pharmaceutics16081009 - 30 Jul 2024
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Abstract
Blood vessels are essential for maintaining tumor growth, progression, and metastasis, yet the tumor vasculature is under a constant state of remodeling. Since the tumor vasculature is an attractive therapeutic target, there is a need to predict the dynamic changes in intratumoral fluid [...] Read more.
Blood vessels are essential for maintaining tumor growth, progression, and metastasis, yet the tumor vasculature is under a constant state of remodeling. Since the tumor vasculature is an attractive therapeutic target, there is a need to predict the dynamic changes in intratumoral fluid pressure and velocity that occur across the tumor microenvironment (TME). The goal of this study was to obtain insight into perfusion anisotropy within lung tumors. To achieve this goal, we used the perfusion marker Hoechst 33342 and vascular endothelial marker CD31 to stain tumor sections from C57BL/6 mice harboring Lewis lung carcinoma tumors on their flank. Vasculature, capillary diameter, and permeability distribution were extracted at different time points along the tumor growth curve. A computational model was generated by applying a unique modeling approach based on the smeared physical fields (Kojic Transport Model, KTM). KTM predicts spatial and temporal changes in intratumoral pressure and fluid velocity within the growing tumor. Anisotropic perfusion occurs within two domains: capillary and extracellular space. Anisotropy in tumor structure causes the nonuniform distribution of pressure and fluid velocity. These results provide insights regarding local vascular distribution for optimal drug dosing and delivery to better predict distribution and duration of retention within the TME. Full article
(This article belongs to the Special Issue Nano-Drug Delivery Systems for Targeting the Tumor Microenvironment and Simultaneously Overcoming Drug Resistance Properties)
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19 pages, 17538 KiB  
Article
A Platelet-Powered Drug Delivery System for Enhancing Chemotherapy Efficacy for Liver Cancer Using the Trojan Horse Strategy
by Hao Huang, Xiaoping Wang, Ziqing Gao, Hongyi Bao, Xiaopeng Yuan, Chao Chen, Donglin Xia and Xiangqian Wang
Pharmaceutics 2024, 16(7), 905; https://doi.org/10.3390/pharmaceutics16070905 - 5 Jul 2024
Viewed by 861
Abstract
Optimizing the delivery and penetration of nano-sized drugs within liver cancer sites, along with remodeling the tumor microenvironment, is crucial for enhancing the efficacy of chemotherapeutic agents. For this study, a platelet (PLT)-mediated nanodrug delivery system (DASA+ATO@PLT) was developed to improve the effectiveness [...] Read more.
Optimizing the delivery and penetration of nano-sized drugs within liver cancer sites, along with remodeling the tumor microenvironment, is crucial for enhancing the efficacy of chemotherapeutic agents. For this study, a platelet (PLT)-mediated nanodrug delivery system (DASA+ATO@PLT) was developed to improve the effectiveness of chemotherapy. This system delivers nano-sized dasatinib and atovaquone specifically to liver tumor sites and facilitates intra-tumoral permeation upon release. Through JC-1, immunohistochemistry, and DNA damage analyses, the therapeutic effect of DASA+ATO@PLT was assessed. In vitro simulation and intravital imaging were carried out to determine the accumulation of dasatinib and atovaquone in liver tumor sites. The experiment demonstrated the accumulation of dasatinib and atovaquone in tumor sites, followed by deep permeation in the tumor microenvironment with the assistance of PLTs, while simultaneously revealing the ability of DASA+ATO@PLT to remodel the liver cancer microenvironment (overcoming hypoxia) and enhance chemotherapeutic efficacy. This system utilizes the natural tumor recognition ability of PLTs and enhances the chemo-immunotherapeutic effect through targeted delivery of nano-chemotherapeutic drugs to the tumor, resulting in effective accumulation and infiltration. The PLT-mediated nanodrug delivery system serves as a “Trojan horse” to carry therapeutic drugs as cargo and deliver them to target cells, leading to favorable outcomes. Full article
(This article belongs to the Special Issue Nano-Drug Delivery Systems for Targeting the Tumor Microenvironment and Simultaneously Overcoming Drug Resistance Properties)
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Review

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27 pages, 6292 KiB  
Review
Improving the Efficacy of Common Cancer Treatments via Targeted Therapeutics towards the Tumour and Its Microenvironment
by Daniel Cecchi, Nolan Jackson, Wayne Beckham and Devika B. Chithrani
Pharmaceutics 2024, 16(2), 175; https://doi.org/10.3390/pharmaceutics16020175 - 26 Jan 2024
Viewed by 1913
Abstract
Cancer is defined as the uncontrolled proliferation of heterogeneous cell cultures in the body that develop abnormalities and mutations, leading to their resistance to many forms of treatment. Left untreated, these abnormal cell growths can lead to detrimental and even fatal complications for [...] Read more.
Cancer is defined as the uncontrolled proliferation of heterogeneous cell cultures in the body that develop abnormalities and mutations, leading to their resistance to many forms of treatment. Left untreated, these abnormal cell growths can lead to detrimental and even fatal complications for patients. Radiation therapy is involved in around 50% of cancer treatment workflows; however, it presents significant recurrence rates and normal tissue toxicity, given the inevitable deposition of the dose to the surrounding healthy tissue. Chemotherapy is another treatment modality with excessive normal tissue toxicity that significantly affects patients’ quality of life. To improve the therapeutic efficacy of radiotherapy and chemotherapy, multiple conjunctive modalities have been proposed, which include the targeting of components of the tumour microenvironment inhibiting tumour spread and anti-therapeutic pathways, increasing the oxygen content within the tumour to revert the hypoxic nature of the malignancy, improving the local dose deposition with metal nanoparticles, and the restriction of the cell cycle within radiosensitive phases. The tumour microenvironment is largely responsible for inhibiting nanoparticle capture within the tumour itself and improving resistance to various forms of cancer therapy. In this review, we discuss the current literature surrounding the administration of molecular and nanoparticle therapeutics, their pharmacokinetics, and contrasting mechanisms of action. The review aims to demonstrate the advancements in the field of conjugated nanomaterials and radiotherapeutics targeting, inhibiting, or bypassing the tumour microenvironment to promote further research that can improve treatment outcomes and toxicity rates. Full article
(This article belongs to the Special Issue Nano-Drug Delivery Systems for Targeting the Tumor Microenvironment and Simultaneously Overcoming Drug Resistance Properties)
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