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Pharmaceutics
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Nanocarriers for Drug Delivery and/or Gene Therapy in Cancer
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Nanocarriers for Drug Delivery and/or Gene Therapy in Cancer

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

Deadline for manuscript submissions: closed (10 August 2022) | Viewed by 28105

Special Issue Editors

Dr. Bianca Gǎlǎţeanu

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Guest Editor
Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, Bucharest, Romania
Interests: colon cancer research; nanoscaled drug delivery systems; tumor-on-chip; liquid biopsy; pharmacogenomics; personalized medicine
Special Issues, Collections and Topics in MDPI journals
Dr. Marieta Costache

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Guest Editor
Department of Biochemistry and Molecular biology, Faculty of Biology, University of Bucharest, Bucharest, Romania
Interests: cancer research; regenerative medicine; genomics and transcriptomics
Dr. Faisal Raza

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Guest Editor
School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China
Interests: biomimetic nanomedicine; polymeric nanoparticle; drug delivery; cancer; tumor microenvironment; biomaterials; cancer nanomedicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Currently, cancer is the second leading cause of death worldwide and, therefore, there is an urgent demand for the discovery of novel therapeutic strategies, with superior anticancer proprieties. Nanobiotechnology knowledge has significantly contributed to the development of genuine nanosized and nanostructured biomaterials for biomedical purposes, particularly in the field of drug delivery systems. Complex nanosystems that exhibit attractive physicochemical properties, possess versatile and tunable functionality for the controlled, targeted, and circumstantially triggered delivery of therapy have recently been developed. Moreover, effective delivery systems that can overcome the numerous biological barriers associated with gene delivery to target cells have been proposed. Considering that substantial progress has been made in the development of plasmid DNA, mRNA, microRNA, small interfering RNA, and antisense oligonucleotides, non-viral gene delivery nanosystems hold great promise in cancer therapy. Following a bio-inspired approach, the validation of these smart nanocarriers inside biomimetic tumor-on-chip platforms that emulate the human tumor microenvironment could deliver clinically-relevant and decision-worthy insights.

This Special Issue will highlight current progress in the development of nanocarriers for drug delivery or gene therapy in cancer. In this regard, we would like to invite members of academic and scientific communities to contribute original papers or reviews on the development, characterization, and possible applications of the nanocarriers for drug delivery or non-viral gene therapy delivery systems. We encourage the submission of manuscripts approaching both in vitro and in vivo studies with potential approaches of tumor-on-chip cutting-edge technology.

Dr. Bianca Gǎlǎţeanu
Dr. Marieta Costache
Dr. Faisal Raza
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

  • nanocarriers for drugs delivery
  • non-viral gene therapy delivery systems
  • cancer therapy approach
  • tumor-on-chip platforms

Published Papers (9 papers)

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Research

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14 pages, 2807 KiB  
Article
Biosynthetic Silver Nanoparticles Inhibit the Malignant Behavior of Gastric Cancer Cells and Enhance the Therapeutic Effect of 5-Fluorouracil by Promoting Intracellular ROS Generation and Apoptosis
by Jingwen Yuan, Shahid Ullah Khan, Jiajun Luo, Yue Jiang, Yu Yang, Junfeng Yan and Qiang Tong
Pharmaceutics 2022, 14(10), 2109; https://doi.org/10.3390/pharmaceutics14102109 - 02 Oct 2022
Cited by 7 | Viewed by 1328
Abstract
(1) Background: Gastric cancer (GC) is the fourth leading cause of cancer death worldwide. Silver nanoparticles (Ag-NPs) have been increasingly used in the diagnosis and treatment of cancer due to their physicochemical properties. This study investigated the role of a kind of biosynthetic [...] Read more.
(1) Background: Gastric cancer (GC) is the fourth leading cause of cancer death worldwide. Silver nanoparticles (Ag-NPs) have been increasingly used in the diagnosis and treatment of cancer due to their physicochemical properties. This study investigated the role of a kind of biosynthetic silver nanoparticle (b-Ag) in the development of GC, the enhancement of 5-fluorouracil (5F), and its mechanism. (2) Methods: X-ray, transmission electron microscopy (TEM), and UV absorbance were used to detect the characterizations of AgNPs. CCK8, Colony formation and a Transwell assay were performed to confirm the malignant behaviors of GC. DCFH-DA and DHE were used to detect intracellular reactive oxygen species (ROS). Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression of apoptosis-related genes. (3) Results: Compared with the chemosynthetic silver nanoparticles (c-Ag), b-Ag had a stronger cytokilling effect, and it had a better inhibition on the malignant phenotype of GC when combined with 5F. The b-Ag increased the expression of Bax and P53 while decreasing the expression of Bcl2. It also promoted the generation of intracellular ROS. (4) Conclusions: By promoting cell apoptosis and increasing intracellular ROS, b-Ag inhibited the development of GC and enhanced the inhibition of 5F on GC. Full article
(This article belongs to the Special Issue Nanocarriers for Drug Delivery and/or Gene Therapy in Cancer)
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14 pages, 2324 KiB  
Article
Design of GSH-Responsive Curcumin Nanomicelles for Oesophageal Cancer Therapy
by Zhaoming Ma, Xuzhu Gao, Faisal Raza, Hajra Zafar, Guanhong Huang, Yunyun Yang, Feng Shi, Deqiang Wang and Xia He
Pharmaceutics 2022, 14(9), 1802; https://doi.org/10.3390/pharmaceutics14091802 - 27 Aug 2022
Cited by 9 | Viewed by 1481
Abstract
Oesophageal cancer is a malignant tumor with high morbidity and mortality. Surgical treatment, radiotherapy, and chemotherapy are the most common treatment methods for oesophageal cancer. However, traditional chemotherapy drugs have poor targeting performance and cause serious adverse drug reactions. In this study, a [...] Read more.
Oesophageal cancer is a malignant tumor with high morbidity and mortality. Surgical treatment, radiotherapy, and chemotherapy are the most common treatment methods for oesophageal cancer. However, traditional chemotherapy drugs have poor targeting performance and cause serious adverse drug reactions. In this study, a GSH-sensitive material, ATRA-SS-HA, was developed and self-assembled with curcumin, a natural polyphenol antitumor drug, into nanomicelles Cur@ATRA-SS-HA. The micelles had a suitable particle size, excellent drug loading, encapsulation rate, stability, biocompatibility, and stable release behaviour. In the tumor microenvironment, GSH induced disulfide bond rupture in Cur@ATRA-SS-HA and promoted the release of curcumin, improving tumor targeting. Following GSH-induced release, the curcumin IC50 value was significantly lower than that of free curcumin and better than that of 5-FU. In vivo pharmacokinetic experiments showed that the drug-loaded nanomicelles exhibited better metabolic behaviour than free drugs, which greatly increased the blood concentration of curcumin and increased the half-life of the drug. The design of the nanomicelle provides a novel clinical treatment for oesophageal cancer. Full article
(This article belongs to the Special Issue Nanocarriers for Drug Delivery and/or Gene Therapy in Cancer)
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20 pages, 2520 KiB  
Article
pH Sensitive Pluronic Acid/Agarose-Hydrogels as Controlled Drug Delivery Carriers: Design, Characterization and Toxicity Evaluation
by Mariam Aslam, Kashif Barkat, Nadia Shamshad Malik, Mohammed S. Alqahtani, Irfan Anjum, Ikrima Khalid, Ume Ruqia Tulain, Nitasha Gohar, Hajra Zafar, Ana Cláudia Paiva-Santos and Faisal Raza
Pharmaceutics 2022, 14(6), 1218; https://doi.org/10.3390/pharmaceutics14061218 - 08 Jun 2022
Cited by 17 | Viewed by 2362
Abstract
The objective of this study was to fabricate and evaluate a pH sensitive cross-linked polymeric network through the free radical polymerization technique for the model drug, cyclophosphamide, used in the treatment of non-Hodgkin’s lymphoma. The Hydrogels were prepared using a polymeric blend of [...] Read more.
The objective of this study was to fabricate and evaluate a pH sensitive cross-linked polymeric network through the free radical polymerization technique for the model drug, cyclophosphamide, used in the treatment of non-Hodgkin’s lymphoma. The Hydrogels were prepared using a polymeric blend of agarose, Pluronic acid, glutaraldehyde, and methacrylic acid. The prepared hydrogels were characterized for drug loading (%), swelling pattern, release behavior, the ingredient’s compatibility, structural evaluation, thermal integrity, and toxicity evaluation in rabbits. The new polymer formation was evident from FTIR findings. The percentage loaded into the hydrogels was in the range of 58.65–75.32%. The developed hydrogels showed significant differences in swelling dynamics and drug release behavior in simulated intestinal fluid (SIF) when compared with simulated gastric fluid (SGF). The drug release was persistent and performed in a controlled manner for up to 24 h. A toxicity study was conducted on white albino rabbits. The developed hydrogels did not show any signs of ocular, skin, or oral toxicity; therefore, these hydrogels can be regarded as safe and potential carriers for controlled drug delivery in biomedical applications. Full article
(This article belongs to the Special Issue Nanocarriers for Drug Delivery and/or Gene Therapy in Cancer)
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19 pages, 4456 KiB  
Article
Lactate-Loaded Nanoparticles Induce Glioma Cytotoxicity and Increase the Survival of Rats Bearing Malignant Glioma Brain Tumor
by Víctor Chavarria, Emma Ortiz-Islas, Alelí Salazar, Verónica Pérez-de la Cruz, Alejandra Espinosa-Bonilla, Rubén Figueroa, Alma Ortíz-Plata, Julio Sotelo, Francisco Javier Sánchez-García and Benjamín Pineda
Pharmaceutics 2022, 14(2), 327; https://doi.org/10.3390/pharmaceutics14020327 - 29 Jan 2022
Cited by 6 | Viewed by 2895
Abstract
A glioblastoma is an aggressive form of a malignant glial-derived tumor with a poor prognosis despite multimodal therapy approaches. Lactate has a preponderant role in the tumor microenvironment, playing an immunoregulatory role as well as being a carbon source for tumor growth. Lactate [...] Read more.
A glioblastoma is an aggressive form of a malignant glial-derived tumor with a poor prognosis despite multimodal therapy approaches. Lactate has a preponderant role in the tumor microenvironment, playing an immunoregulatory role as well as being a carbon source for tumor growth. Lactate homeostasis depends on the proper functioning of intracellular lactate regulation systems, such as transporters and enzymes involved in its synthesis and degradation, with evidence that an intracellular lactate overload generates metabolic stress on tumor cells and tumor cell death. We propose that the delivery of a lactate overload carried in nanoparticles, allowing the intracellular release of lactate, would compromise the survival of tumor cells. We synthesized and characterized silica and titania nanoparticles loaded with lactate to evaluate the cellular uptake, metabolic activity, pH modification, and cytotoxicity on C6 cells under normoxia and chemical hypoxia, and, finally, determined the survival of an orthotopic malignant glioma model after in situ administration. A dose-dependent reduction in metabolic activity of treated cells under normoxia was found, but not under hypoxia, independent of glucose concentration. Lactated-loaded silica nanoparticles were highly cytotoxic (58.1% of dead cells) and generated significant supernatant acidification. In vivo, lactate-loaded silica nanoparticles significantly increased the median survival time of malignant glioma-bearing rats (p = 0.005) when administered in situ. These findings indicate that lactate-loaded silica nanoparticles are cytotoxic on glioma cells in vitro and in vivo. Full article
(This article belongs to the Special Issue Nanocarriers for Drug Delivery and/or Gene Therapy in Cancer)
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12 pages, 19230 KiB  
Article
Smart Shockwave Responsive Titania-Based Nanoparticles for Cancer Treatment
by Veronica Vighetto, Luisa Racca, Marta Canta, Joana C. Matos, Bianca Dumontel, Maria Clara Gonçalves and Valentina Cauda
Pharmaceutics 2021, 13(9), 1423; https://doi.org/10.3390/pharmaceutics13091423 - 08 Sep 2021
Cited by 11 | Viewed by 2075
Abstract
Nanomedicine is an emerging treatment approach for many cancers, characterized by having high sensitivity and selectivity for tumor cells and minimal toxic effects induced by the conventional chemotherapeutics. In these context, smart nanoparticles (NPs) are getting increasingly relevant in the development of new [...] Read more.
Nanomedicine is an emerging treatment approach for many cancers, characterized by having high sensitivity and selectivity for tumor cells and minimal toxic effects induced by the conventional chemotherapeutics. In these context, smart nanoparticles (NPs) are getting increasingly relevant in the development of new therapies. NPs with specific chemical composition and/or structure and being stimuli-responsive to magnetic, light or ultrasound waves are new promising tools. In the present work, amorphous-titania propyl-amine functionalized (a-TiO2-NH2) NPs, coated with bovine serum albumin (BSA), are stimulated with high energy shock waves to induce cytotoxic effects in cancer cells. First, a new method to coat a-TiO2-NH2 NPs with BSA (a-TiO2-NH2/BSA) was proposed, allowing for a high dispersion and colloidal stability in a cell culture media. The a-TiO2-NH2/BSA NPs showed no cancer cell cytotoxicity. In a second step, the use of shock waves to stimulate a-TiO2-NH2/BSA NPs, was evaluated and optimized. A systematic study was performed in in vitro cell culture aiming to impair the cancer cell viability: NP concentrations, time steps and single versus multiple shock waves treatments were studied. The obtained results highlighted the relevance of NPs design and administration time point with respect to the shock wave treatment and allow to hypothesize mechanical damages to cells. Full article
(This article belongs to the Special Issue Nanocarriers for Drug Delivery and/or Gene Therapy in Cancer)
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21 pages, 6808 KiB  
Article
Preclinical In Vitro Studies with 3D Spheroids to Evaluate Cu(DDC)2 Containing Liposomes for the Treatment of Neuroblastoma
by Friederike Hartwig, Monika Köll-Weber and Regine Süss
Pharmaceutics 2021, 13(6), 894; https://doi.org/10.3390/pharmaceutics13060894 - 17 Jun 2021
Cited by 12 | Viewed by 2713
Abstract
Preclinical in vitro studies of drug candidates for anticancer therapy are generally conducted on well-established 2D cell models. Unfortunately, these models are unable to mimic the properties of in vivo tumors. However, in vitro 3D models (spheroids) have been proven to be superior [...] Read more.
Preclinical in vitro studies of drug candidates for anticancer therapy are generally conducted on well-established 2D cell models. Unfortunately, these models are unable to mimic the properties of in vivo tumors. However, in vitro 3D models (spheroids) have been proven to be superior in reflecting the tumor microenvironment. Diethyldithiocarbamate (DDC−) is the active metabolite of Disulfiram, an approved drug for alcoholism and repurposed for cancer treatment. DDC− binds copper in a molar ratio of 2:1 resulting in a water-insoluble Cu(DDC)2 complex exhibiting anticancer activities. Delivery of the Cu(DDC)2 complex using nanoparticulate carriers provides decisive advantages for a parental application. In this study, an injectable liposomal Cu(DDC)2 formulation was developed and the toxicity was compared with a 2D neuroblastoma and a 3D neuroblastoma cell model. Our results indicate that Cu(DDC)2 liposomes complied with the size requirements of nanoparticles for intravenous injection and demonstrated high drug to lipid ratios as well as colloidal stability upon storage. Furthermore, an efficient cytotoxic effect on neuroblastoma 2D cell cultures and a very promising and even more pronounced effect on 3D cell cultures in terms of neuroblastoma monoculture and neuroblastoma co-culture with primary cell lines was proven, highly encouraging the use of Cu(DDC)2 liposomes for anticancer therapy. Full article
(This article belongs to the Special Issue Nanocarriers for Drug Delivery and/or Gene Therapy in Cancer)
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Review

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19 pages, 2970 KiB  
Review
Nanocarriers Used in Drug Delivery to Enhance Immune System in Cancer Therapy
by Giovanna C. N. B. Lôbo, Karen L. R. Paiva, Ana Luísa G. Silva, Marina M. Simões, Marina A. Radicchi and Sônia N. Báo
Pharmaceutics 2021, 13(8), 1167; https://doi.org/10.3390/pharmaceutics13081167 - 28 Jul 2021
Cited by 21 | Viewed by 6818
Abstract
Cancer, a group of diseases responsible for the second largest cause of global death, is considered one of the main public health problems today. Despite the advances, there are still difficulties in the development of more efficient cancer therapies and fewer adverse effects [...] Read more.
Cancer, a group of diseases responsible for the second largest cause of global death, is considered one of the main public health problems today. Despite the advances, there are still difficulties in the development of more efficient cancer therapies and fewer adverse effects for the patients. In this context, nanobiotechnology, a materials science on a nanometric scale specified for biology, has been developing and acquiring prominence for the synthesis of nanocarriers that provide a wide surface area in relation to volume, better drug delivery, and a maximization of therapeutic efficiency. Among these carriers, the ones that stand out are those focused on the activation of the immune system. The literature demonstrates the importance of this system for anticancer therapy, given that the best treatment for this disease also activates the immune system to recognize, track, and destroy all remaining tumor cells. Full article
(This article belongs to the Special Issue Nanocarriers for Drug Delivery and/or Gene Therapy in Cancer)
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26 pages, 4829 KiB  
Review
The Multifaceted Role of Extracellular Vesicles in Glioblastoma: microRNA Nanocarriers for Disease Progression and Gene Therapy
by Natalia Simionescu, Radu Zonda, Anca Roxana Petrovici and Adriana Georgescu
Pharmaceutics 2021, 13(7), 988; https://doi.org/10.3390/pharmaceutics13070988 - 29 Jun 2021
Cited by 14 | Viewed by 2917
Abstract
Glioblastoma (GB) is the most aggressive form of brain cancer in adults, characterized by poor survival rates and lack of effective therapies. MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression post-transcriptionally through specific pairing with target messenger RNAs (mRNAs). Extracellular vesicles [...] Read more.
Glioblastoma (GB) is the most aggressive form of brain cancer in adults, characterized by poor survival rates and lack of effective therapies. MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression post-transcriptionally through specific pairing with target messenger RNAs (mRNAs). Extracellular vesicles (EVs), a heterogeneous group of cell-derived vesicles, transport miRNAs, mRNAs and intracellular proteins, and have been shown to promote horizontal malignancy into adjacent tissue, as well as resistance to conventional therapies. Furthermore, GB-derived EVs have distinct miRNA contents and are able to penetrate the blood–brain barrier. Numerous studies have attempted to identify EV-associated miRNA biomarkers in serum/plasma and cerebrospinal fluid, but their collective findings fail to identify reliable biomarkers that can be applied in clinical settings. However, EVs carrying specific miRNAs or miRNA inhibitors have great potential as therapeutic nanotools in GB, and several studies have investigated this possibility on in vitro and in vivo models. In this review, we discuss the role of EVs and their miRNA content in GB progression and resistance to therapy, with emphasis on their potential as diagnostic, prognostic and disease monitoring biomarkers and as nanocarriers for gene therapy. Full article
(This article belongs to the Special Issue Nanocarriers for Drug Delivery and/or Gene Therapy in Cancer)
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24 pages, 1478 KiB  
Review
Bioengineered siRNA-Based Nanoplatforms Targeting Molecular Signaling Pathways for the Treatment of Triple Negative Breast Cancer: Preclinical and Clinical Advancements
by Dima Hattab and Athirah Bakhtiar
Pharmaceutics 2020, 12(10), 929; https://doi.org/10.3390/pharmaceutics12100929 - 29 Sep 2020
Cited by 18 | Viewed by 3603
Abstract
Triple negative breast cancer (TNBC) is one of the most aggressive types of breast cancer. Owing to the absenteeism of hormonal receptors expressed at the cancerous breast cells, hormonal therapies and other medications targeting human epidermal growth factor receptor 2 (HER2) are ineffective [...] Read more.
Triple negative breast cancer (TNBC) is one of the most aggressive types of breast cancer. Owing to the absenteeism of hormonal receptors expressed at the cancerous breast cells, hormonal therapies and other medications targeting human epidermal growth factor receptor 2 (HER2) are ineffective in TNBC patients, making traditional chemotherapeutic agents the only current appropriate regimen. Patients’ predisposition to relapse and metastasis, chemotherapeutics’ cytotoxicity and resistance and poor prognosis of TNBC necessitates researchers to investigate different novel-targeted therapeutics. The role of small interfering RNA (siRNA) in silencing the genes/proteins that are aberrantly overexpressed in carcinoma cells showed great potential as part of TNBC therapeutic regimen. However, targeting specificity, siRNA stability, and delivery efficiency cause challenges in the progression of this application clinically. Nanotechnology was highlighted as a promising approach for encapsulating and transporting siRNA with high efficiency-low toxicity profile. Advances in preclinical and clinical studies utilizing engineered siRNA-loaded nanotherapeutics for treatment of TNBC were discussed. Specific and selective targeting of diverse signaling molecules/pathways at the level of tumor proliferation and cell cycle, tumor invasion and metastasis, angiogenesis and tumor microenvironment, and chemotherapeutics’ resistance demonstrated greater activity via integration of siRNA-complexed nanoparticles. Full article
(This article belongs to the Special Issue Nanocarriers for Drug Delivery and/or Gene Therapy in Cancer)
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