Cancers

Editorial

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2 pages, 183 KiB

Open AccessEditorial

Special Issue on Cancer Smart Nanomedicine

by Marina Pinheiro and Ammad Ahmad Farooqi

Cancers 2023, 15(22), 5344; https://doi.org/10.3390/cancers15225344 - 9 Nov 2023

Viewed by 691

Abstract

In this Special Issue entitled “Cancer Smart Nanomedicine”, we have gathered high-quality contributions related to the fascinating field of nanomedicine [...] Full article

(This article belongs to the Special Issue Cancer Smart Nanomedicine)

Research

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17 pages, 2765 KiB

Open AccessArticle

Improving the Effect of Cancer Cells Irradiation with X-rays and High-Energy Protons Using Bimetallic Palladium-Platinum Nanoparticles with Various Nanostructures

by Bartosz Klebowski, Malgorzata Stec, Joanna Depciuch, Agnieszka Panek, Dawid Krzempek, Wiktor Komenda, Adrianna Gałuszka-Bulaga, Anna Pajor-Swierzy, Jarek Baran and Magdalena Parlinska-Wojtan

Cancers 2022, 14(23), 5899; https://doi.org/10.3390/cancers14235899 - 29 Nov 2022

Cited by 4 | Viewed by 2042

Abstract

Nano-sized radiosensitizers can be used to increase the effectiveness of radiation-based anticancer therapies. In this study, bimetallic, ~30 nm palladium-platinum nanoparticles (PdPt NPs) with different nanostructures (random nano-alloy NPs and ordered core-shell NPs) were prepared. Scanning transmission electron microscopy (STEM), selected area electron [...] Read more.

Nano-sized radiosensitizers can be used to increase the effectiveness of radiation-based anticancer therapies. In this study, bimetallic, ~30 nm palladium-platinum nanoparticles (PdPt NPs) with different nanostructures (random nano-alloy NPs and ordered core-shell NPs) were prepared. Scanning transmission electron microscopy (STEM), selected area electron diffraction (SAED), energy-dispersive X-ray spectroscopy (EDS), zeta potential measurements, and nanoparticle tracking analysis (NTA) were used to provide the physicochemical characteristics of PdPt NPs. Then, PdPt NPs were added to the cultures of colon cancer cells and normal colon epithelium cells in individually established non-toxic concentrations and irradiated with the non-harmful dose of X-rays/protons. Cell viability before and after PdPt NPs-(non) assisted X-ray/proton irradiation was evaluated by MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. Flow cytometry was used to assess cell apoptosis. The results showed that PdPt NPs significantly enhanced the effect of irradiation on cancer cells. It was noticed that nano-alloy PdPt NPs possess better radiosensitizing properties compared to PtPd core-shell NPs, and the combined effect against cancer cells was c.a. 10% stronger for X-ray than for proton irradiation. Thus, the radio-enhancing features of differently structured PdPt NPs indicate their potential application for the improvement of the effectiveness of radiation-based anticancer therapies. Full article

(This article belongs to the Special Issue Cancer Smart Nanomedicine)

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22 pages, 5107 KiB

Open AccessArticle

Targeted Transposition of Minicircle DNA Using Single-Chain Antibody Conjugated Cyclodextrin-Modified Poly (Propylene Imine) Nanocarriers

by Willi Jugel, Stefanie Tietze, Jennifer Daeg, Dietmar Appelhans, Felix Broghammer, Achim Aigner, Michael Karimov, Gabriele Schackert and Achim Temme

Cancers 2022, 14(8), 1925; https://doi.org/10.3390/cancers14081925 - 11 Apr 2022

Cited by 1 | Viewed by 2739

Abstract

Among non-viral vectors, cationic polymers, such as poly(propylene imine) (PPI), play a prominent role in nucleic acid delivery. However, limitations of polycationic polymer-based DNA delivery systems are (i) insufficient target specificity, (ii) unsatisfactory transgene expression, and (iii) undesired transfer of therapeutic DNA into [...] Read more.

Among non-viral vectors, cationic polymers, such as poly(propylene imine) (PPI), play a prominent role in nucleic acid delivery. However, limitations of polycationic polymer-based DNA delivery systems are (i) insufficient target specificity, (ii) unsatisfactory transgene expression, and (iii) undesired transfer of therapeutic DNA into non-target cells. We developed single-chain antibody fragment (scFv)-directed hybrid polyplexes for targeted gene therapy of prostate stem cell antigen (PSCA)-positive tumors. Besides mono-biotinylated PSCA-specific single-chain antibodies (scFv(AM1-P-BAP)) conjugated to neutravidin, the hybrid polyplexes comprise β-cyclodextrin-modified PPI as well as biotin/maltose-modified PPI as carriers for minicircle DNAs encoding for Sleeping Beauty transposase and a transposon encoding the gene of interest. The PSCA-specific hybrid polyplexes efficiently delivered a GFP gene in PSCA-positive tumor cells, whereas control hybrid polyplexes showed low gene transfer efficiency. In an experimental gene therapy approach, targeted transposition of a codon-optimized p53 into p53-deficient HCT116^{p53−/−/PSCA} cells demonstrated decreased clonogenic survival when compared to mock controls. Noteworthily, p53 transposition in PTEN-deficient H4^PSCA glioma cells caused nearly complete loss of clonogenic survival. These results demonstrate the feasibility of combining tumor-targeting hybrid polyplexes and Sleeping Beauty gene transposition, which, due to the modular design, can be extended to other target genes and tumor entities. Full article

(This article belongs to the Special Issue Cancer Smart Nanomedicine)

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15 pages, 2184 KiB

Open AccessArticle

Ag/Au Bimetallic Nanoparticles Trigger Different Cell Death Pathways and Affect Damage Associated Molecular Pattern Release in Human Cell Lines

by Hector Katifelis, Maria-Paraskevi Nikou, Iuliia Mukha, Nadiia Vityuk, Nefeli Lagopati, Christina Piperi, Ammad Ahmad Farooqi, Natassa Pippa, Efstathios P. Efstathopoulos and Maria Gazouli

Cancers 2022, 14(6), 1546; https://doi.org/10.3390/cancers14061546 - 17 Mar 2022

Cited by 23 | Viewed by 3366

Abstract

Apoptosis induction is a common therapeutic approach. However, many cancer cells are resistant to apoptotic death and alternative cell death pathways including pyroptosis and necroptosis need to be triggered. At the same time, danger signals that include HMGB1 and HSP70 can be secreted/released [...] Read more.

Apoptosis induction is a common therapeutic approach. However, many cancer cells are resistant to apoptotic death and alternative cell death pathways including pyroptosis and necroptosis need to be triggered. At the same time, danger signals that include HMGB1 and HSP70 can be secreted/released by damaged cancer cells that boost antitumor immunity. We studied the cytotoxic effects of AgAu NPs, Ag NPs and Au NPs with regard to the programmed cell death (apoptosis, necroptosis, pyroptosis) and the secretion/release of HSP70 and HMGB1. Cancer cell lines were incubated with 30, 40 and 50 μg/mL of AgAu NPs, Ag NPs and Au NPs. Cytotoxicity was estimated using the MTS assay, and mRNA fold change of CASP1, CASP3, BCL-2, ZPB1, HMGB1, HSP70, CXCL8, CSF1, CCL20, NLRP3, IL-1β and IL-18 was used to investigate the associated programmed cell death. Extracellular levels of HMGB1 and IL-1β were investigated using the ELISA technique. The nanoparticles showed a dose dependent toxicity. Pyroptosis was triggered for LNCaP and MDA-MB-231 cells, and necroptosis for MDA-MB-231 cells. HCT116 cells experience apoptotic death and show increased levels of extracellular HMGB1. Our results suggest that in a manner dependent of the cellular microenvironment, AgAu NPs trigger mixed programmed cell death in P53 deficient MDA-MB-231 cells, while they also trigger IL-1β release in MDA-MB-231 and LNCaP cells and release of HMGB1 in HCT116 cells. Full article

(This article belongs to the Special Issue Cancer Smart Nanomedicine)

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20 pages, 2560 KiB

Open AccessArticle

Smart Modification on Magnetic Nanoparticles Dramatically Enhances Their Therapeutic Properties

by Nuria Lafuente-Gómez, Paula Milán-Rois, David García-Soriano, Yurena Luengo, Marco Cordani, Hernán Alarcón-Iniesta, Gorka Salas and Álvaro Somoza

Cancers 2021, 13(16), 4095; https://doi.org/10.3390/cancers13164095 - 14 Aug 2021

Cited by 16 | Viewed by 3544

Abstract

Magnetic nanoparticles (MNP) are employed as nanocarriers and in magnetic hyperthermia (MH) for the treatment of cancers. Herein, a smart drug delivery system composed of MNP functionalized with the cytotoxic drug gemcitabine (MNP-GEM) has been thoroughly evaluated. The linker employed is based on [...] Read more.

Magnetic nanoparticles (MNP) are employed as nanocarriers and in magnetic hyperthermia (MH) for the treatment of cancers. Herein, a smart drug delivery system composed of MNP functionalized with the cytotoxic drug gemcitabine (MNP-GEM) has been thoroughly evaluated. The linker employed is based on a disulfide bond and allows the controlled release of GEM under a highly reducing environment, which is frequently present in the cytoplasm of tumor cells. The stability, MH, and the interaction with plasma proteins of the nanoparticles are evaluated, highlighting their great potential for biological applications. Their cytotoxicity is assessed in three pancreatic cancer cell lines with different sensitivity to GEM, including the generation of reactive oxygen species (ROS), the effects on the cell cycle, and the mechanisms of cell death involved. Remarkably, the proposed nanocarrier is better internalized than unmodified nanoparticles, and it is particularly effective in PANC-1 cells, resistant to GEM, but not in non-tumoral keratinocytes. Additionally, its combination with MH produces a synergistic cytotoxic effect in all cancer cell lines tested. In conclusion, MNP-GEM presents a promising potential for treating pancreatic cancer, due to multiple parameters, such as reduced binding to plasma proteins, increased internalization, and synergistic activity when combined with MH. Full article

(This article belongs to the Special Issue Cancer Smart Nanomedicine)

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Review

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19 pages, 2829 KiB

Open AccessReview

Polyphenol-Based Nanoparticles: A Promising Frontier for Enhanced Colorectal Cancer Treatment

by Hicham Wahnou, Bertrand Liagre, Vincent Sol, Hicham El Attar, Rukset Attar, Mounia Oudghiri, Raphaël Emmanuel Duval and Youness Limami

Cancers 2023, 15(15), 3826; https://doi.org/10.3390/cancers15153826 - 27 Jul 2023

Cited by 13 | Viewed by 3280

Abstract

Colorectal cancer (CRC) poses a significant challenge in healthcare, necessitating the exploration of novel therapeutic strategies. Natural compounds such as polyphenols with inherent anticancer properties have gained attention as potential therapeutic agents. This review highlights the need for novel therapeutic approaches in CRC, [...] Read more.

Colorectal cancer (CRC) poses a significant challenge in healthcare, necessitating the exploration of novel therapeutic strategies. Natural compounds such as polyphenols with inherent anticancer properties have gained attention as potential therapeutic agents. This review highlights the need for novel therapeutic approaches in CRC, followed by a discussion on the synthesis of polyphenols-based nanoparticles. Various synthesis techniques, including dynamic covalent bonding, non-covalent bonding, polymerization, chemical conjugation, reduction, and metal-polyphenol networks, are explored. The mechanisms of action of these nanoparticles, encompassing passive and active targeting mechanisms, are also discussed. The review further examines the intrinsic anticancer activity of polyphenols and their enhancement through nano-based delivery systems. This section explores the natural anticancer properties of polyphenols and investigates different nano-based delivery systems, such as micelles, nanogels, liposomes, nanoemulsions, gold nanoparticles, mesoporous silica nanoparticles, and metal–organic frameworks. The review concludes by emphasizing the potential of nanoparticle-based strategies utilizing polyphenols for CRC treatment and highlights the need for future research to optimize their efficacy and safety. Overall, this review provides valuable insights into the synthesis, mechanisms of action, intrinsic anticancer activity, and enhancement of polyphenols-based nanoparticles for CRC treatment. Full article

(This article belongs to the Special Issue Cancer Smart Nanomedicine)

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33 pages, 2561 KiB

Open AccessReview

Metastatic Breast Cancer: Review of Emerging Nanotherapeutics

by Ranga Dissanayake, Rheal Towner and Marya Ahmed

Cancers 2023, 15(11), 2906; https://doi.org/10.3390/cancers15112906 - 25 May 2023

Cited by 9 | Viewed by 4147

Abstract

Metastases of breast cancer (BC) are often referred to as stage IV breast cancer due to their severity and high rate of mortality. The median survival time of patients with metastatic BC is reduced to 3 years. Currently, the treatment regimens for metastatic [...] Read more.

Metastases of breast cancer (BC) are often referred to as stage IV breast cancer due to their severity and high rate of mortality. The median survival time of patients with metastatic BC is reduced to 3 years. Currently, the treatment regimens for metastatic BC are similar to the primary cancer therapeutics and are limited to conventional chemotherapy, immunotherapy, radiotherapy, and surgery. However, metastatic BC shows organ-specific complex tumor cell heterogeneity, plasticity, and a distinct tumor microenvironment, leading to therapeutic failure. This issue can be successfully addressed by combining current cancer therapies with nanotechnology. The applications of nanotherapeutics for both primary and metastatic BC treatments are developing rapidly, and new ideas and technologies are being discovered. Several recent reviews covered the advancement of nanotherapeutics for primary BC, while also discussing certain aspects of treatments for metastatic BC. This review provides comprehensive details on the recent advancement and future prospects of nanotherapeutics designed for metastatic BC treatment, in the context of the pathological state of the disease. Furthermore, possible combinations of current treatment with nanotechnology are discussed, and their potential for future transitions in clinical settings is explored. Full article

(This article belongs to the Special Issue Cancer Smart Nanomedicine)

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24 pages, 3084 KiB

Open AccessReview

Connection of Cancer Exosomal LncRNAs, Sponging miRNAs, and Exosomal Processing and Their Potential Modulation by Natural Products

by Ya-Ting Chuang, Jun-Ping Shiau, Jen-Yang Tang, Ammad Ahmad Farooqi, Fang-Rong Chang, Yi-Hong Tsai, Ching-Yu Yen and Hsueh-Wei Chang

Cancers 2023, 15(8), 2215; https://doi.org/10.3390/cancers15082215 - 9 Apr 2023

Cited by 2 | Viewed by 2319

Abstract

Cancerous exosomes contain diverse biomolecules that regulate cancer progression. Modulating exosome biogenesis with clinical drugs has become an effective strategy for cancer therapy. Suppressing exosomal processing (assembly and secretion) may block exosomal function to reduce the proliferation of cancer cells. However, the information [...] Read more.

Cancerous exosomes contain diverse biomolecules that regulate cancer progression. Modulating exosome biogenesis with clinical drugs has become an effective strategy for cancer therapy. Suppressing exosomal processing (assembly and secretion) may block exosomal function to reduce the proliferation of cancer cells. However, the information on natural products that modulate cancer exosomes lacks systemic organization, particularly for exosomal long noncoding RNAs (lncRNAs). There is a gap in the connection between exosomal lncRNAs and exosomal processing. This review introduces the database (LncTarD) to explore the potential of exosomal lncRNAs and their sponging miRNAs. The names of sponging miRNAs were transferred to the database (miRDB) for the target prediction of exosomal processing genes. Moreover, the impacts of lncRNAs, sponging miRNAs, and exosomal processing on the tumor microenvironment (TME) and natural-product-modulating anticancer effects were then retrieved and organized. This review sheds light on the functions of exosomal lncRNAs, sponging miRNAs, and exosomal processing in anticancer processes. It also provides future directions for the application of natural products when regulating cancerous exosomal lncRNAs. Full article

(This article belongs to the Special Issue Cancer Smart Nanomedicine)

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19 pages, 1333 KiB

Open AccessReview

Nanomedicine for the Delivery of RNA in Cancer

by Michele Ghidini, Sandra G. Silva, Jessica Evangelista, Maria Luísa C. do Vale, Ammad Ahmad Farooqi and Marina Pinheiro

Cancers 2022, 14(11), 2677; https://doi.org/10.3390/cancers14112677 - 28 May 2022

Cited by 9 | Viewed by 3176

Abstract

The complexity, and the diversity of the different types of cancers allied to the tendency to form metastasis make treatment efficiency so tricky and often impossible due to the advanced stage of the disease in the diagnosis. In recent years, due to tremendous [...] Read more.

The complexity, and the diversity of the different types of cancers allied to the tendency to form metastasis make treatment efficiency so tricky and often impossible due to the advanced stage of the disease in the diagnosis. In recent years, due to tremendous scientific breakthroughs, we have witnessed exponential growth in the elucidation of mechanisms that underlie carcinogenesis and metastasis. The development of more selective therapies made it possible to improve cancer treatment. Although interdisciplinary research leads to encouraging results, scientists still have a long exploration journey. RNA technology represents a promise as a therapeutic intervention for targeted gene silencing in cancer, and there are already some RNA-based formulations in clinical trials. However, the use of RNA as a therapeutic tool presents severe limitations, mainly related to its low stability and poor cellular uptake. Thus, the use of nanomedicine employing nanoparticles to encapsulate RNA may represent a suitable platform to address the major challenges hampering its therapeutic application. In this review, we have revisited the potential of RNA and RNA-associated therapies to fight cancer, also providing, as support, a general overview of nanoplatforms for RNA delivery. Full article

(This article belongs to the Special Issue Cancer Smart Nanomedicine)

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