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Nanoparticle-Based Combination Therapy and Diagnosis for Cancer

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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (15 June 2022) | Viewed by 19080

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Special Issue Editors

Prof. Elena Reddi

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Guest Editor

Department of Biology, University of Padova, 35121 Padova, Italy.
Interests: cancer; nanomedicine and cancer; drug delivery; combination therapy; photodynamic cancer therapy; polymeric and biomimetic nanoparticles

Dr. Francesca Moret

E-Mail Website
Co-Guest Editor

Department of Biology, Università degli Studi di Padova, 35122 Padua, Italy
Interests: cancer nanomedicine; biodegradable and biomimetic nanoparticles; cell-based delivery systems; cancer stem cell therapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In cancerous tissues the coexistence of populations of cells with different metabolism, proliferation rate, invasiveness, metastatic potential, sensitivity to drugs, and development of resistance is often responsible for therapy failure when using a single agent. Cancer treatments based on combinations of drugs and/or different treatment modalities increase the chances of eliminating cells with different phenotypes and minimizing unwanted toxic effects on normal tissues by exploiting possible additive/synergic interactions that allow for the reduction of drug doses without losing therapeutic efficacy.

However, the advantages brought by combination therapies are fully exploited provided that optimized drug concentration ratios can reach the tumor in a timely and spatially controlled manner. This requirement is difficult to meet, especially when using standard drug formulations, because the different physico-chemical properties of the molecules determine asynchronous kinetics of drug accumulation and release in the tumor. In this context, the use of nanoplatforms that can accommodate molecules with different properties at predetermined ratios offers the opportunity for more controlled and precise delivery of drugs into target tissue, strongly increasing the benefit of combination therapies. Of note, nanoparticles can also be conceived for the simultaneous delivery of therapeutic and diagnostic agents for theranostic applications.

This Special Issue will collect contributions on the latest advances on the use of nanoparticles for the simultaneous delivery of drugs in combination therapy or therapeutic and diagnostic agents for the simultaneous treatment and detection of cancers, and will bring into focus the potential of nanotechnology to improve efficacy and decrease side effects of cancer treatments.

Prof. Elena Reddi
Dr. Francesca Moret
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. Cancers is an international peer-reviewed open access semimonthly 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

nanomedicine
combination therapy
theranostic nanoparticles
synergistic interaction

Published Papers (7 papers)

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Research

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18 pages, 3830 KiB

Open AccessArticle

Functionalized Hybrid Iron Oxide–Gold Nanoparticles Targeting Membrane Hsp70 Radiosensitize Triple-Negative Breast Cancer Cells by ROS-Mediated Apoptosis

by Zhiyuan Wu, Stefan Stangl, Alicia Hernandez-Schnelzer, Fei Wang, Morteza Hasanzadeh Kafshgari, Ali Bashiri Dezfouli and Gabriele Multhoff

Cancers 2023, 15(4), 1167; https://doi.org/10.3390/cancers15041167 - 11 Feb 2023

Cited by 9 | Viewed by 2020

Abstract

Triple-negative breast cancer (TNBC) a highly aggressive tumor entity with an unfavorable prognosis, is treated by multimodal therapies, including ionizing radiation (IR). Radiation-resistant tumor cells, as well as induced normal tissue toxicity, contribute to the poor clinical outcome of the disease. In this study, we investigated the potential of novel hybrid iron oxide (Fe₃O₄)-gold (Au) nanoparticles (FeAuNPs) functionalized with the heat shock protein 70 (Hsp70) tumor-penetrating peptide (TPP) and coupled via a PEG4 linker (TPP-PEG4-FeAuNPs) to improve tumor targeting and uptake of NPs and to break radioresistance in TNBC cell lines 4T1 and MDA-MB-231. Hsp70 is overexpressed in the cytosol and abundantly presented on the cell membrane (mHsp70) of highly aggressive tumor cells, including TNBCs, but not on corresponding normal cells, thus providing a tumor-specific target. The Fe₃O₄ core of the NPs can serve as a contrast agent enabling magnetic resonance imaging (MRI) of the tumor, and the nanogold shell radiosensitizes tumor cells by the release of secondary electrons (Auger electrons) upon X-ray irradiation. We demonstrated that the accumulation of TPP-PEG4-FeAuNPs into mHsp70-positive TNBC cells was superior to that of non-conjugated FeAuNPs and FeAuNPs functionalized with a non-specific, scrambled peptide (NGL). After a 24 h co-incubation period of 4T1 and MDA-MB-231 cells with TPP-PEG4-FeAuNPs, but not with control hybrid NPs, ionizing irradiation (IR) causes a cell cycle arrest at G2/M and induces DNA double-strand breaks, thus triggering apoptotic cell death. Since the radiosensitizing effect was completely abolished in the presence of the ROS inhibitor N-acetyl-L-cysteine (NAC), we assume that the TPP-PEG4-FeAuNP-induced apoptosis is mediated via an increased production of ROS. Full article

(This article belongs to the Special Issue Nanoparticle-Based Combination Therapy and Diagnosis for Cancer)

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26 pages, 6355 KiB

Open AccessFeature PaperArticle

HSA-Binding Prodrugs-Based Nanoparticles Endowed with Chemo and Photo-Toxicity against Breast Cancer

by Valentina Rapozzi, Francesca Moret, Luca Menilli, Andrea Guerrini, Daniele Tedesco, Marina Naldi, Manuela Bartolini, Mariachiara Gani, Sonia Zorzet, Marta Columbaro, Celeste Milani, Cecilia Martini, Claudia Ferroni and Greta Varchi

Cancers 2022, 14(4), 877; https://doi.org/10.3390/cancers14040877 - 10 Feb 2022

Cited by 8 | Viewed by 2699

Abstract

Exploiting the tumor environment features (EPR effect, elevated glutathione, reactive oxygen species levels) might allow attaining a selective and responsive carrier capable of improving the therapeutic outcome. To this purpose, the in situ covalent binding of drugs and nanoparticles to circulating human serum albumin (HSA) might represent a pioneering approach to achieve an effective strategy. This study describes the synthesis, in vitro and in vivo evaluation of bioresponsive HSA-binding nanoparticles (MAL-PTX₂S@Pba), co-delivering two different paclitaxel (PTX) prodrugs and the photosensitizer pheophorbide a (Pba), for the combined photo- and chemo-treatment of breast cancer. Stable and reproducible MAL-PTX₂S@Pba nanoparticles with an average diameter of 82 nm and a PTX/Pba molar ratio of 2.5 were obtained by nanoprecipitation. The in vitro 2D combination experiments revealed that MAL-PTX₂S@Pba treatment induces a strong inhibition of cell viability of MDA-MB-231, MCF7 and 4T1 cell lines, whereas 3D experiments displayed different trends: while MAL-PTX₂S@Pba effectiveness was confirmed against MDA-MB-231 spheroids, the 4T1 model exhibited marked resistance. Lastly, despite using a low PTX-PDT regimen (e.g., 8.16 mg/Kg PTX and 2.34 mg/Kg Pba), our formulation showed to foster primary tumor reduction and curb lung metastases growth in 4T1 tumor-bearing mice, thus setting the basis for further preclinical validations. Full article

(This article belongs to the Special Issue Nanoparticle-Based Combination Therapy and Diagnosis for Cancer)

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13 pages, 2138 KiB

Open AccessArticle

Combined Fluorescence-Guided Resection and Intracavitary Thermotherapy with Superparamagnetic Iron-Oxide Nanoparticles for Recurrent High-Grade Glioma: Case Series with Emphasis on Complication Management

by Michael Schwake, Michael Müther, Ann-Katrin Bruns, Bastian Zinnhardt, Nils Warneke, Markus Holling, Stephanie Schipmann, Benjamin Brokinkel, Johannes Wölfer, Walter Stummer and Oliver Grauer

Cancers 2022, 14(3), 541; https://doi.org/10.3390/cancers14030541 - 21 Jan 2022

Cited by 5 | Viewed by 1736

Abstract

Background: Concepts improving local tumor control in high-grade glioma (HGG) are desperately needed. The aim of this study is to report an extended series of cases treated with a combination of 5-ALA-fluorescence-guided resection (FGR) and intracavitary thermotherapy with superparamagnetic iron oxide nanoparticles (SPION). Methods: We conducted a single-center retrospective review of all recurrent HGG treated with FGR and intracavitary thermotherapy (n = 18). Patients underwent six hyperthermia sessions in an alternating magnetic field and received additional adjuvant therapies on a case-by-case basis. Results: Nine patients were treated for first tumor recurrence; all other patients had suffered at least two recurrences. Nine patients received combined radiotherapy and thermotherapy. The median progression-free survival was 5.5 (95% CI: 4.67–6.13) months and median overall survival was 9.5 (95% CI: 7.12–11.79) months. No major side effects were observed during active treatment. Thirteen patients (72%) developed cerebral edema and more clinical symptoms during follow-up and were initially treated with dexamethasone. Six (33%) of these patients underwent surgical removal of nanoparticles due to refractory edema. Conclusions: The combination of FGR and intracavitary thermotherapy with SPION provides a new treatment option for improving local tumor control in recurrent HGG. The development of cerebral edema is a major issue requiring further refinements of the treatment protocol. Full article

(This article belongs to the Special Issue Nanoparticle-Based Combination Therapy and Diagnosis for Cancer)

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Review

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31 pages, 3221 KiB

Open AccessReview

Overview of Nanoparticle-Based Approaches for the Combination of Photodynamic Therapy (PDT) and Chemotherapy at the Preclinical Stage

by Luca Menilli, Celeste Milani, Elena Reddi and Francesca Moret

Cancers 2022, 14(18), 4462; https://doi.org/10.3390/cancers14184462 - 14 Sep 2022

Cited by 13 | Viewed by 2585

Abstract

The widespread diffusion of photodynamic therapy (PDT) as a clinical treatment for solid tumors is mainly limited by the patient’s adverse reaction (skin photosensivity), insufficient light penetration in deeply seated neoplastic lesions, unfavorable photosensitizers (PSs) biodistribution, and photokilling efficiency due to PS aggregation in biological environments. Despite this, recent preclinical studies reported on successful combinatorial regimes of PSs with chemotherapeutics obtained through the drugs encapsulation in multifunctional nanometric delivery systems. The aim of the present review deals with the punctual description of several nanosystems designed not only with the objective of co-transporting a PS and a chemodrug for combination therapy, but also with the goal of improving the therapeutic efficacy by facing the main critical issues of both therapies (side effects, scarce tumor oxygenation and light penetration, premature drug clearance, unspecific biodistribution, etc.). Therefore, particular attention is paid to the description of bio-responsive drugs and nanoparticles (NPs), targeted nanosystems, biomimetic approaches, and upconverting NPs, including analyzing the therapeutic efficacy of the proposed photo-chemotherapeutic regimens in in vitro and in vivo cancer models. Full article

(This article belongs to the Special Issue Nanoparticle-Based Combination Therapy and Diagnosis for Cancer)

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38 pages, 3459 KiB

Open AccessReview

Theranostic Potentials of Gold Nanomaterials in Hematological Malignancies

by Md Salman Shakil, Mahruba Sultana Niloy, Kazi Mustafa Mahmud, Mohammad Amjad Kamal and Md Asiful Islam

Cancers 2022, 14(13), 3047; https://doi.org/10.3390/cancers14133047 - 21 Jun 2022

Cited by 4 | Viewed by 2832

Abstract

Hematological malignancies (HMs) are a heterogeneous group of blood neoplasia generally characterized by abnormal blood-cell production. Detection of HMs-specific molecular biomarkers (e.g., surface antigens, nucleic acid, and proteomic biomarkers) is crucial in determining clinical states and monitoring disease progression. Early diagnosis of HMs, followed by an effective treatment, can remarkably extend overall survival of patients. However, traditional and advanced HMs’ diagnostic strategies still lack selectivity and sensitivity. More importantly, commercially available chemotherapeutic drugs are losing their efficacy due to adverse effects, and many patients develop resistance against these drugs. To overcome these limitations, the development of novel potent and reliable theranostic agents is urgently needed to diagnose and combat HMs at an early stage. Recently, gold nanomaterials (GNMs) have shown promise in the diagnosis and treatment of HMs. Magnetic resonance and the surface-plasmon-resonance properties of GNMs have made them a suitable candidate in the diagnosis of HMs via magnetic-resonance imaging and colorimetric or electrochemical sensing of cancer-specific biomarkers. Furthermore, GNMs-based photodynamic therapy, photothermal therapy, radiation therapy, and targeted drug delivery enhanced the selectivity and efficacy of anticancer drugs or drug candidates. Therefore, surface-tuned GNMs could be used as sensitive, reliable, and accurate early HMs, metastatic HMs, and MRD-detection tools, as well as selective, potent anticancer agents. However, GNMs may induce endothelial leakage to exacerbate cancer metastasis. Studies using clinical patient samples, patient-derived HMs models, or healthy-animal models could give a precise idea about their theranostic potential as well as biocompatibility. The present review will investigate the theranostic potential of vectorized GNMs in HMs and future challenges before clinical theranostic applications in HMs. Full article

(This article belongs to the Special Issue Nanoparticle-Based Combination Therapy and Diagnosis for Cancer)

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20 pages, 4487 KiB

Open AccessReview

Synergistic Action of Immunotherapy and Nanotherapy against Cancer Patients Infected with SARS-CoV-2 and the Use of Artificial Intelligence

by Tanvi Gupta, Tilahun Ayane Debele, Yu-Feng Wei, Anish Gupta, Mohd Murtaza and Wen-Pin Su

Cancers 2022, 14(1), 213; https://doi.org/10.3390/cancers14010213 - 02 Jan 2022

Cited by 1 | Viewed by 3176

Abstract

Since 2019, the SARS-CoV-2 pandemic has caused a huge chaos throughout the world and the major threat has been possessed by the immune-compromised individuals involving the cancer patients; their weakened immune response makes them vulnerable and susceptible to the virus. The oncologists as well as their patients are facing many problems for their treatment sessions as they need to postpone their surgery, chemotherapy, or radiotherapy. The approach that could be adopted especially for the cancer patients is the amalgamation of immunotherapy and nanotherapy which can reduce the burden on the healthcare at this peak time of the infection. There is also a need to predict or analyze the data of cancer patients who are at a severe risk of being exposed to an infection in order to reduce the mortality rate. The use of artificial intelligence (AI) could be incorporated where the real time data will be available to the physicians according to the different patient’s clinical characteristics and their past treatments. With this data, it will become easier for them to modify or replace the treatment to increase the efficacy against the infection. The combination of an immunotherapy and nanotherapy will be targeted to treat the cancer patients diagnosed with SARS-CoV-2 and the AI will act as icing on the cake to monitor, predict and analyze the data of the patients to improve the treatment regime for the most vulnerable patients. Full article

(This article belongs to the Special Issue Nanoparticle-Based Combination Therapy and Diagnosis for Cancer)

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25 pages, 1461 KiB

Open AccessReview

Nanobiotechnology and Immunotherapy: Two Powerful and Cooperative Allies against Cancer

by Francesco Mainini, Francesca De Santis, Giovanni Fucà, Massimo Di Nicola, Licia Rivoltini and Michael Eccles

Cancers 2021, 13(15), 3765; https://doi.org/10.3390/cancers13153765 - 27 Jul 2021

Cited by 7 | Viewed by 2730

Abstract

A number of novel cancer therapies have recently emerged that have rapidly moved from the bench to the clinic. Onco-immunotherapies, such as immune checkpoint blockade inhibitors and adoptive cell therapies, have revolutionized the field, since they provide a way to induce strong anti-tumor immune responses, which are able to fight cancer effectively. However, despite showing great efficacy in hematological and some solid tumors, unresponsiveness, development of therapy resistance and the development of serious adverse effects, limit their capacity to impact the vast majority of tumors. Nanoparticle-based delivery systems are versatile vehicles for a wide variety of molecular cargoes and provide an innovative strategy to improve conventional onco-immunotherapies. They can be finely tuned to release their contents in the tumor microenvironment, or to deliver combinations of adjuvants and antigens in the case of nanovaccines. In this review, we summarize the recent advancements in the field of nanobiotechnology, to remodel the tumor microenvironment and to enhance immunotherapies. Full article

(This article belongs to the Special Issue Nanoparticle-Based Combination Therapy and Diagnosis for Cancer)

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