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

Deadline for manuscript submissions: closed (20 June 2023) | Viewed by 23610

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Dr. Manuel A. N. Coelho

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LEPABE - Laboratory for Process Engineering, Environment, Biotechnology and Energy, Rua. Dr. Roberto Frias, 4200-465 Porto, Portugal
Interests: nanoparticle biocompatibility; nanoparticle/drug cell uptake mechanisms; drug delivery; cancer diagnostics and therapy
Special Issues, Collections and Topics in MDPI journals

Dr. Sílvia Castro Coelho

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Guest Editor

LEPABE - Laboratory for Process Engineering, Environment, Biotechnology and Energy, Rua. Dr. Roberto Frias, 4200-465 Porto, Portugal
Interests: design and production of inorganic/organic nanosystems for pharmaceutical and food applications; nanobiotechnology and development/characterization of functionalized gold nanoparticles for cancer therapy and diagnosis; delivery systems (nanoparticles, polymeric/gold particle carriers); microencapsulation processes by electrospinning technique
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In recent years, nanocarriers have attracted a significant amount of attention in various biomedical applications, such as site-specific drug delivery and imaging diagnosis. Nano-sized systems based on polymers, metals, and lipids present a high potential to improve the retention and release of chemotherapeutics in cancer cells and tissues, minimize the associated systemic side effects, and overcome multi-drug resistance. They exhibit distinctive physicochemical characteristics, such as biocompatibility, chemical stability, and a reactive surface. These promising vehicles are expected to overcome the limitations of chemotherapeutic agents, such as a lack in biodistribution as well as poor solubility and stability.

Authors are kindly invited to submit original papers, communications, and reviews regarding the potential applications of different types of nanocarriers as drug delivery systems for cancer therapy and diagnosis to be published in this Special Issue of Pharmaceutics.

Dr. Manuel A. N. Coelho
Dr. Sílvia Castro Coelho
Guest Editors

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Keywords

nanocarriers
supramolecular structures
drug delivery systems
treatment
diagnosis
polymer conjugated
biomaterials
biocompatible

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Related Special Issues

Nanocarriers for Cancer Therapy and Diagnosis, 3rd Edition in Pharmaceutics
Nanocarriers for Cancer Therapy and Diagnosis in Pharmaceutics (12 articles)

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Research

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15 pages, 3002 KiB

Open AccessArticle

A Novel Formulation of Asparaginase Encapsulated into Virus-like Particles of Brome Mosaic Virus: In Vitro and In Vivo Evidence

by Francisca Villanueva-Flores, Ana Ruth Pastor, Laura A. Palomares and Alejandro Huerta-Saquero

Pharmaceutics 2023, 15(9), 2260; https://doi.org/10.3390/pharmaceutics15092260 - 31 Aug 2023

Cited by 1 | Viewed by 1569

Abstract

The interest in plant-derived virus-like particles (pVLPs) for the design of a new generation of nanocarriers is based on their lack of infection for humans, their immunostimulatory properties to fight cancer cells, and their capability to contain and release cargo molecules. Asparaginase (ASNase) is an FDA-approved drug to treat acute lymphoblastic leukemia (LLA); however, it exhibits high immunogenicity which often leads to discontinuation of treatment. In previous work, we encapsulated ASNase into bacteriophage P22-based VLPs through genetic-directed design to form the ASNase-P22 nanobioreactors. In this work, a commercial ASNase was encapsulated into brome mosaic virus-like particles (BMV-VLPs) to form stable ASNase-BMV nanobioreactors. According to our results, we observed that ASNase-BMV nanobioreactors had similar cytotoxicity against MOLT-4 and Reh cells as the commercial drug. In vivo assays showed a higher specific anti-ASNase IgG response in BALB/c mice immunized with ASNase encapsulated into BMV-VLPs compared with those immunized with free ASNase. Nevertheless, we also detected a high and specific IgG response against BMV capsids on both ASNase-filled capsids (ASNase-BMV) and empty BMV capsids. Despite the fact that our in vivo studies showed that the BMV-VLPs stimulate the immune response either empty or with cargo proteins, the specific cytotoxicity against leukemic cells allows us to propose ASNase-BMV as a potential novel formulation for LLA treatment where in vitro and in vivo evidence of functionality is provided. Full article

(This article belongs to the Special Issue Nanocarriers for Cancer Therapy and Diagnosis, 2nd Edition)

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25 pages, 7410 KiB

Open AccessArticle

Microfluidic-Assisted ZIF-Silk-Polydopamine Nanoparticles as Promising Drug Carriers for Breast Cancer Therapy

by Zijian Gao, Muhamad Hawari Mansor, Natalie Winder, Secil Demiral, Jordan Maclnnes, Xiubo Zhao and Munitta Muthana

Pharmaceutics 2023, 15(7), 1811; https://doi.org/10.3390/pharmaceutics15071811 - 24 Jun 2023

Cited by 5 | Viewed by 2539

Abstract

Metal–organic frameworks (MOFs) are heralded as potential nanoplatforms for biomedical applications. Zeolitic imidazolate framework-8 (ZIF-8), as one of the most well known MOFs, has been widely applied as a drug delivery carrier for cancer therapy. However, the application of ZIF-8 nanoparticles as a therapeutic agent has been hindered by the challenge of how to control the release behaviour of anti-cancer zinc ions to cancer cells. In this paper, we designed microfluidic-assisted core-shell ZIF-8 nanoparticles modified with silk fibroin (SF) and polydopamine (PDA) for sustained release of zinc ions and curcumin (CUR) and tested these in vitro in various human breast cancer cells. We report that microfluidic rapid mixing is an efficient method to precisely control the proportion of ZIF-8, SF, PDA, and CUR in the nanoparticles by simply adjusting total flow rates (from 1 to 50 mL/min) and flow rate ratios. Owing to sufficient and rapid mixing during microfluidic-assisted nanoprecipitation, our designer CUR@ZIF-SF-PDA nanoparticles had a desired particle size of 170 nm with a narrow size distribution (PDI: 0.08), which is much smaller than nanoparticles produced using traditional magnetic stirrer mixing method (over 1000 nm). Moreover, a properly coated SF layer successfully enhanced the capability of ZIF-8 as a reservoir of zinc ions. Meanwhile, the self-etching reaction between ZIF-8 and PDA naturally induced a pH-responsive release of zinc ions and CUR to a therapeutic level in the MDA-MB-231, SK-BR-3, and MCF-7 breast cancer cell lines, resulting in a high cellular uptake efficiency, cytotoxicity, and cell cycle arrest. More importantly, the high biocompatibility of designed CUR@ZIF-SF-PDA nanoparticles remained low in cytotoxicity on AD-293 non-cancer cells. We demonstrate the potential of prepared CUR@ZIF-SF-PDA nanoparticles as promising carriers for the controlled release of CUR and zinc ions in breast cancer therapy. Full article

(This article belongs to the Special Issue Nanocarriers for Cancer Therapy and Diagnosis, 2nd Edition)

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23 pages, 3543 KiB

Open AccessArticle

Combination of Chemotherapy and Mild Hyperthermia Using Targeted Nanoparticles: A Potential Treatment Modality for Breast Cancer

by Ishdeep Kaur, Terence Tieu, Veerasikku G. Deepagan, Muhammad A. Ali, Fahad Alsunaydih, David Rudd, Maliheh A. Moghaddam, Laure Bourgeois, Timothy E. Adams, Kristofer J. Thurecht, Mehmet Yuce, Anna Cifuentes-Rius and Nicolas H. Voelcker

Pharmaceutics 2023, 15(5), 1389; https://doi.org/10.3390/pharmaceutics15051389 - 30 Apr 2023

Cited by 5 | Viewed by 2672

Abstract

Despite the clinical benefits that chemotherapeutics has had on the treatment of breast cancer, drug resistance remains one of the main obstacles to curative cancer therapy. Nanomedicines allow therapeutics to be more targeted and effective, resulting in enhanced treatment success, reduced side effects, and the possibility of minimising drug resistance by the co-delivery of therapeutic agents. Porous silicon nanoparticles (pSiNPs) have been established as efficient vectors for drug delivery. Their high surface area makes them an ideal carrier for the administration of multiple therapeutics, providing the means to apply multiple attacks to the tumour. Moreover, immobilising targeting ligands on the pSiNP surface helps direct them selectively to cancer cells, thereby reducing harm to normal tissues. Here, we engineered breast cancer-targeted pSiNPs co-loaded with an anticancer drug and gold nanoclusters (AuNCs). AuNCs have the capacity to induce hyperthermia when exposed to a radiofrequency field. Using monolayer and 3D cell cultures, we demonstrate that the cell-killing efficacy of combined hyperthermia and chemotherapy via targeted pSiNPs is 1.5-fold higher than applying monotherapy and 3.5-fold higher compared to using a nontargeted system with combined therapeutics. The results not only demonstrate targeted pSiNPs as a successful nanocarrier for combination therapy but also confirm it as a versatile platform with the potential to be used for personalised medicine. Full article

(This article belongs to the Special Issue Nanocarriers for Cancer Therapy and Diagnosis, 2nd Edition)

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19 pages, 3483 KiB

Open AccessArticle

Immunogenic Cell Death Photothermally Mediated by Erythrocyte Membrane-Coated Magnetofluorescent Nanocarriers Improves Survival in Sarcoma Model

by Ailton Antonio Sousa-Junior, Francyelli Mello-Andrade, João Victor Ribeiro Rocha, Tácio Gonçalves Hayasaki, Juliana Santana de Curcio, Lívia do Carmo Silva, Ricardo Costa de Santana, Eliana Martins Lima, Cléver Gomes Cardoso, Elisângela de Paula Silveira-Lacerda, Sebastião Antonio Mendanha and Andris Figueiroa Bakuzis

Pharmaceutics 2023, 15(3), 943; https://doi.org/10.3390/pharmaceutics15030943 - 14 Mar 2023

Cited by 8 | Viewed by 2363

Abstract

Inducing immunogenic cell death (ICD) during cancer therapy is a major challenge that might significantly improve patient survival. The purpose of this study was to develop a theranostic nanocarrier, capable both of conveying a cytotoxic thermal dose when mediating photothermal therapy (PTT) after its intravenous delivery, and of consequently inducing ICD, improving survival. The nanocarrier consists of red blood cell membranes (RBCm) embedding the near-infrared dye IR-780 (IR) and camouflaging Mn-ferrite nanoparticles (RBCm-IR-Mn). The RBCm-IR-Mn nanocarriers were characterized by size, morphology, surface charge, magnetic, photophysical, and photothermal properties. Their photothermal conversion efficiency was found to be size- and concentration-dependent. Late apoptosis was observed as the cell death mechanism for PTT. Calreticulin and HMGB1 protein levels increased for in vitro PTT with temperature around 55 °C (ablative regime) but not for 44 °C (hyperthermia), suggesting ICD elicitation under ablation. RBCm-IR-Mn were then intravenously administered in sarcoma S180-bearing Swiss mice, and in vivo ablative PTT was performed five days later. Tumor volumes were monitored for the subsequent 120 days. RBCm-IR-Mn-mediated PTT promoted tumor regression in 11/12 animals, with an overall survival rate of 85% (11/13). Our results demonstrate that the RBCm-IR-Mn nanocarriers are great candidates for PTT-induced cancer immunotherapy. Full article

(This article belongs to the Special Issue Nanocarriers for Cancer Therapy and Diagnosis, 2nd Edition)

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15 pages, 1746 KiB

Open AccessArticle

Exploring RAB11A Pathway to Hinder Chronic Myeloid Leukemia-Induced Angiogenesis In Vivo

by Catarina Roma-Rodrigues, Alexandra R. Fernandes and Pedro V. Baptista

Pharmaceutics 2023, 15(3), 742; https://doi.org/10.3390/pharmaceutics15030742 - 23 Feb 2023

Cited by 3 | Viewed by 2196

Abstract

Neoangiogenesis is generally correlated with poor prognosis, due to the promotion of cancer cell growth, invasion and metastasis. The progression of chronic myeloid leukemia (CML) is frequently associated with an increased vascular density in bone marrow. From a molecular point of view, the small GTP-binding protein Rab11a, involved in the endosomal slow recycling pathway, has been shown to play a crucial role for the neoangiogenic process at the bone marrow of CML patients, by controlling the secretion of exosomes by CML cells, and by regulating the recycling of vascular endothelial factor receptors. The angiogenic potential of exosomes secreted by the CML cell line K562 has been previously observed using the chorioallantoic membrane (CAM) model. Herein, gold nanoparticles (AuNPs) were functionalized with an anti-RAB11A oligonucleotide (AuNP@RAB11A) to downregulate RAB11A mRNA in K562 cell line which showed a 40% silencing of the mRNA after 6 h and 14% silencing of the protein after 12 h. Then, using the in vivo CAM model, these exosomes secreted by AuNP@RAB11A incubated K562 did not present the angiogenic potential of those secreted from untreated K562 cells. These results demonstrate the relevance of Rab11 for the neoangiogenesis mediated by tumor exosomes, whose deleterious effect may be counteracted via targeted silencing of these crucial genes; thus, decreasing the number of pro-tumoral exosomes at the tumor microenvironment. Full article

(This article belongs to the Special Issue Nanocarriers for Cancer Therapy and Diagnosis, 2nd Edition)

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19 pages, 5381 KiB

Open AccessArticle

Synthesis and Characterization of Supermagnetic Nanocomposites Coated with Pluronic F127 as a Contrast Agent for Biomedical Applications

by Maria Janina Carrera Espinoza, Kuen-Song Lin, Meng-Tzu Weng, Sikhumbuzo Charles Kunene, You-Sheng Lin and Chun-Ming Wu

Pharmaceutics 2023, 15(3), 740; https://doi.org/10.3390/pharmaceutics15030740 - 23 Feb 2023

Cited by 6 | Viewed by 2486

Abstract

Nanomedicine has garnered significant interest owing to advances in drug delivery, effectively demonstrated in the treatment of certain diseases. Here, smart supermagnetic nanocomposites based on iron oxide nanoparticles (MNPs) coated with Pluronic F127 (F127) were developed for the delivery of doxorubicin (DOX) to tumor tissues. The XRD patterns for all samples revealed peaks consistent with Fe₃O₄, as shown by their indices (220), (311), (400), (422), (511), and (440), demonstrating that the structure of Fe₃O₄ did not change after the coating process. After loading with DOX, the as-prepared smart nanocomposites demonstrated drug-loading efficiency and drug-loading capacity percentages of 45 ± 0.10 and 17 ± 0.58% for MNP-F127-2-DOX and 65 ± 0.12 and 13 ± 0.79% for MNP-F127-3-DOX, respectively. Moreover, a better DOX release rate was observed under acidic conditions, which may be credited to the pH sensitivity of the polymer. In vitro analysis demonstrated the survival rate of approximately 90% in HepG2 cells treated with PBS and MNP-F127-3 nanocomposites. Furthermore, after treatment with MNP-F127-3-DOX, the survival rate decreased, confirming cellular inhibition. Hence, the synthesized smart nanocomposites showed great promise for drug delivery in liver cancer treatment, overcoming the limitations of traditional therapies. Full article

(This article belongs to the Special Issue Nanocarriers for Cancer Therapy and Diagnosis, 2nd Edition)

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17 pages, 4708 KiB

Open AccessArticle

Role of HIKESHI on Hyperthermia for Castration-Resistant Prostate Cancer and Application of a Novel Magnetic Nanoparticle with Carbon Nanohorn for Magnetic Hyperthermia

by Takashi Nagai, Noriyasu Kawai, Masakazu Gonda, Keitaro Iida, Toshiki Etani, Daichi Kobayashi, Taku Naiki, Aya Naiki-Ito, Ryosuke Ando, Sataro Yamaguchi, Yuto Sugahara, Sakyo Ueno, Kaname Tsutsumiuchi, Toyoko Imae and Takahiro Yasui

Pharmaceutics 2023, 15(2), 626; https://doi.org/10.3390/pharmaceutics15020626 - 13 Feb 2023

Cited by 5 | Viewed by 2185

Abstract

The prognosis of castration-resistant prostate cancer (CRPC) is technically scarce; therefore, a novel treatment for CRPC remains warranted. To this end, hyperthermia (HT) was investigated as an alternative therapy. In this study, the analysis focused on the association between CRPC and heat shock protein nuclear import factor “hikeshi (HIKESHI)”, a factor of heat tolerance. Silencing the HIKESHI expression of 22Rv1 cells (human CRPC cell line) treated with siRNAs inhibited the translocation of heat shock protein 70 from the cytoplasm to the nucleus under heat shock and enhanced the effect of hyperthermia. Moreover, a novel magnetic nanoparticle was developed via binding carbon nanohorn (CNH) and iron oxide nanoparticle (IONP) with 3-aminopropylsilyl (APS). Tumor-bearing model mice implanted with 22 Rv1 cells were examined to determine the effect of magnetic HT (mHT). We locally injected CNH-APS-IONP into the tumor, which was set under an alternative magnetic field and showed that tumor growth in the treatment group was significantly suppressed compared with other groups. This study suggests that HIKESHI silencing enhances the sensitivity of 22Rv1 cells to HT, and CNH-APTES-IONP deserves consideration for mHT. Full article

(This article belongs to the Special Issue Nanocarriers for Cancer Therapy and Diagnosis, 2nd Edition)

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17 pages, 5464 KiB

Open AccessArticle

Tumor-Targeted Erythrocyte Membrane Nanoparticles for Theranostics of Triple-Negative Breast Cancer

by Moon Jung Choi, Yeon Kyung Lee, Kang Chan Choi, Do Hyun Lee, Hwa Yeon Jeong, Seong Jae Kang, Min Woo Kim, Young Myoung You, Chan Su Im, Tae Sup Lee and Yong Serk Park

Pharmaceutics 2023, 15(2), 350; https://doi.org/10.3390/pharmaceutics15020350 - 20 Jan 2023

Cited by 6 | Viewed by 2342

Abstract

Triple-negative breast cancer (TNBC) cells do not contain various receptors for targeted treatment, a reason behind the poor prognosis of this disease. In this study, biocompatible theranostic erythrocyte-derived nanoparticles (EDNs) were developed and evaluated for effective early diagnosis and treatment of TNBC. The anti-cancer drug, doxorubicin (DOX), was encapsulated into the EDNs and diagnostic quantum dots (QDs) were incorporated into the lipid bilayers of EDNs for tumor bio-imaging. Then, anti-epidermal growth factor receptor (EGFR) antibody molecules were conjugated to the surface of EDNs for TNBC targeting (iEDNs). According to the confocal microscopic analyses and biodistribution assay, iEDNs showed a higher accumulation in EGFR-positive MDA-MB-231 cancers in vitro as well as in vivo, compared to untargeted EDNs. iEDNs containing doxorubicin (iEDNs-DOX) showed a stronger inhibition of target tumor growth than untargeted ones. The resulting anti-EGFR iEDNs exhibited strong biocompatibility, prolonged blood circulation, and efficient targeting of TNBC in mice. Therefore, iEDNs may be used as potential TNBC-targeted co-delivery systems for therapeutics and diagnostics. Full article

(This article belongs to the Special Issue Nanocarriers for Cancer Therapy and Diagnosis, 2nd Edition)

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Review

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19 pages, 3040 KiB

Open AccessReview

Molecularly Imprinted Carriers for Diagnostics and Therapy—A Critical Appraisal

by Emilia Balcer, Monika Sobiech and Piotr Luliński

Pharmaceutics 2023, 15(6), 1647; https://doi.org/10.3390/pharmaceutics15061647 - 3 Jun 2023

Cited by 14 | Viewed by 1820

Abstract

Simultaneous diagnostics and targeted therapy provide a theranostic approach, an instrument of personalized medicine—one of the most-promising trends in current medicine. Except for the appropriate drug used during the treatment, a strong focus is put on the development of effective drug carriers. Among the various materials applied in the production of drug carriers, molecularly imprinted polymers (MIPs) are one of the candidates with great potential for use in theranostics. MIP properties such as chemical and thermal stability, together with capability to integrate with other materials are important in the case of diagnostics and therapy. Moreover, the MIP specificity, which is important for targeted drug delivery and bioimaging of particular cells, is a result of the preparation process, conducted in the presence of the template molecule, which often is the same as the target compound. This review focused on the application of MIPs in theranostics. As a an introduction, the current trends in theranostics are described prior to the characterization of the concept of molecular imprinting technology. Next, a detailed discussion of the construction strategies of MIPs for diagnostics and therapy according to targeting and theranostic approaches is provided. Finally, frontiers and future prospects are presented, stating the direction for further development of this class of materials. Full article

(This article belongs to the Special Issue Nanocarriers for Cancer Therapy and Diagnosis, 2nd Edition)

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25 pages, 1688 KiB

Open AccessReview

Exploiting Nanomedicine for Cancer Polychemotherapy: Recent Advances and Clinical Applications

by Elena Boggio, Casimiro Luca Gigliotti, Ian Stoppa, Deepika Pantham, Sara Sacchetti, Roberta Rolla, Margherita Grattarola, Chiara Monge, Stefania Pizzimenti, Umberto Dianzani, Chiara Dianzani and Luigi Battaglia

Pharmaceutics 2023, 15(3), 937; https://doi.org/10.3390/pharmaceutics15030937 - 14 Mar 2023

Cited by 1 | Viewed by 2383

Abstract

The most important limitations of chemotherapeutic agents are severe side effects and the development of multi-drug resistance. Recently, the clinical successes achieved with immunotherapy have revolutionized the treatment of several advanced-stage malignancies, but most patients do not respond and many of them develop immune-related adverse events. Loading synergistic combinations of different anti-tumor drugs in nanocarriers may enhance their efficacy and reduce life-threatening toxicities. Thereafter, nanomedicines may synergize with pharmacological, immunological, and physical combined treatments, and should be increasingly integrated in multimodal combination therapy regimens. The goal of this manuscript is to provide better understanding and key considerations for developing new combined nanomedicines and nanotheranostics. We will clarify the potential of combined nanomedicine strategies that are designed to target different steps of the cancer growth as well as its microenvironment and immunity interactions. Moreover, we will describe relevant experiments in animal models and discuss issues raised by translation in the human setting. Full article

(This article belongs to the Special Issue Nanocarriers for Cancer Therapy and Diagnosis, 2nd Edition)

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