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Biomimetic Nanomedicine for Cancer Therapy and Diagnosis

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

Deadline for manuscript submissions: closed (20 May 2022) | Viewed by 16503

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Dr. Santosh Aryal

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Department of Pharmaceutical Sciences and Health Outcomes, The Ben and Maytee Fisch College of Pharmacy, University of Texas at Tyler, Tyler, TX 75799, USA
Interests: drug delivery; theranostics; cancer nanomedicine; imaging; cancer therapy; extracellular vesicles; exosomes
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Dear Colleagues,

Recent progress in anticancer nanomedicine research has shown future potentials of clinical impact on the diagnosis, treatment, and prevention of cancer, especially with early intervention and precise therapy. Varieties of organic and inorganic nanomaterials have been tagged with drugs and contrast agents for the detection and evaluation of therapeutic progress in cancer. While these nanomedicines show outstanding results in reducing tumor size in rodents, translation of the results to clinical success is limited. Major causes highlighted are limitations in precisely homing to the tumor, nonspecific distribution, and in some cases, the lack of understanding of the in vivo degradation path of ingredients used in nanomedicine synthesis.

The ultimate goal of anticancer nanomedicine is to precisely target cancer to localize anticancer drugs into the deep tumor, minimize the unwanted distribution of cytotoxic agents, enhanced plasma residence, and subsequently safe excretion of excipients used in nanomedicine. A common strategy used to achieve these goals, to some extent, is the surface modification of nanomedicine with polyethylene glycol (PEG), which enhances plasma residence time and decreases their recognition and clearance by the reticuloendothelial system (RES). However, PEGylation also reduces the interaction of the nanoformulation to the target and barrier cells, thus decreasing the drug biodistribution in disease tissues. Therefore, a novel nanoengineering strategy is immensely needed to tackle the limitations of anticancer nanomedicine.

The major barrier in the drug delivery system is the rapid reorganization of nanomedicine as foreign material by the immune system. Therefore, the first strategy to tackle this issue should be focused on design consideration to make the system cooperative to immune cells. In this endeavor, a biomimetic surface modification of nanomedicine using cell ghosts derived from red blood cells, immune cells, platelets, and stem cells has been exploited because it enhances the re-installment of the biological complexity of the original cells on the carrier’s surface. Endogenous cells have the advantage that they are autologous or can be allogenic and immediately available in large numbers. Moreover, the combination of conventional synthetic nanoparticles with natural or biomimetic materials could offer new solutions in the field of drug delivery to overcome their respective shortcomings. Within this background, the aim of this Special Issue on “Biomimetic Nanomedicine for Cancer Therapy and Diagnosis” is to tabulate the research in the area of biomimetic anticancer nanomedicine development using biocomponent, synthetic material, and/or their combinations. Original research papers, communications, review articles, or opinions dealing with the biomimetic anticancer nanomedicines are welcome for this Special Issue.

Prof. Santosh Aryal
Guest Editor

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Keywords

biomimetic
cancer
nanomedicine
drug delivery
imaging
extracellular vesicles
exosomes

Published Papers (6 papers)

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Research

8 pages, 2369 KiB

Open AccessArticle

Novel Use of Hypoxia-Inducible Polymerizable Protein to Augment Chemotherapy for Pancreatic Cancer

by Andrew Gdowski, Hamed Hayatshahi, Rafal Fudala, Rohan Joshi, Jin Liu, Jamboor K. Vishwanatha, Rohan Jeyarajah, Paul Guzik and Amalendu P. Ranjan

Pharmaceutics 2022, 14(1), 128; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14010128 - 05 Jan 2022

Cited by 1 | Viewed by 1817

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies and is the fourth leading cause of cancer-related deaths in the United States. Unfortunately, 80–85% of patients are diagnosed with unresectable, advanced stage tumors. These tumors are incurable and result in a median survival less than approximately six months and an overall 5-year survival rate of less than 7%. Whilst chemotherapy is a critical treatment, cure is not possible without surgical resection. The poor clinical outcomes in PDAC can be partially attributed to its dense desmoplastic stroma, taking up roughly 80% of the tumor mass. The stroma surrounding the tumor disrupts the normal architecture of pancreatic tissue leading to poor vascularization, high intratumoral pressure along with hypoxia and an acidic tumor microenvironment. This complicated microenvironment presents a significant challenge for drug delivery. The current manuscript discusses a novel approach to overcome many of these various obstacles. A complex of gemcitabine (GEM) and hemoglobin S (HbS) was formulated, which self-polymerizes under hypoxic and acidic conditions. When polymerized, HbS has the potential to break the tumor stroma, decrease intratumoral pressure, and therefore improve the treatment efficacy of standard therapy. Intratumoral injection of HbS with a fluorescent small molecule surrogate for GEM into a pancreatic tumor xenograft resulted in improved dissemination of the small molecule throughout the pancreatic tumor. The self-polymerization of HbS + GEM was significantly more effective than either agent individually at decreasing tumor size in an in vivo PDAC mouse model. These findings would suggest a clinical benefit from delivering the complex of GEM and HbS via direct injection by endoscopic ultrasound (EUS). With such a treatment option, patients with locally advanced disease would have the potential to become surgical candidates, offering them a chance for cure. Full article

(This article belongs to the Special Issue Biomimetic Nanomedicine for Cancer Therapy and Diagnosis)

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28 pages, 11148 KiB

Open AccessArticle

Titania Nanosheet Generates Peroxynitrite-Dependent S-Nitrosylation and Enhances p53 Function in Lung Cancer Cells

by Rapeepun Soonnarong, Sucharat Tungsukruthai, Bodee Nutho, Thanyada Rungrotmongkol, Chanida Vinayanuwattikun, Tosapol Maluangnont and Pithi Chanvorachote

Pharmaceutics 2021, 13(8), 1233; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13081233 - 10 Aug 2021

Cited by 5 | Viewed by 2339

Abstract

Metal nanomaterials can enhance the efficacy of current cancer therapies. Here, we show that Ti₀_.8O₂ nanosheets cause cytotoxicity in several lung cancer cells but not in normal cells. The nanosheet-treated cells showed certain apoptosis characteristics. Protein analysis further indicated the activation of the p53-dependent death mechanism. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) analyses revealed the cellular uptake of the nanosheets and the induction of cell morphological change. The nanosheets also exhibited a substantial apoptosis effect on drug-resistant metastatic primary lung cancer cells, and it was found that the potency of the nanosheets was dramatically higher than standard drugs. Ti₀_.8O₂ nanosheets induce apoptosis through a molecular mechanism involving peroxynitrite (ONOO⁻) generation. As peroxynitrite is known to be a potent inducer of S-nitrosylation, we further found that the nanosheets mediated the S-nitrosylation of p53 at C182, resulting in higher protein-protein complex stability, and this was likely to induce the surrounding residues, located in the interface region, to bind more strongly to each other. Molecular dynamics analysis revealed that S-nitrosylation stabilized the p53 dimer with a

Δ G_{bind}^{residue}

of <−1.5 kcal/mol. These results provide novel insight on the apoptosis induction effect of the nanosheets via a molecular mechanism involving S-nitrosylation of the p53 protein, emphasizing the mechanism of action of nanomaterials for cancer therapy. Full article

(This article belongs to the Special Issue Biomimetic Nanomedicine for Cancer Therapy and Diagnosis)

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14 pages, 25163 KiB

Open AccessArticle

Identification of Angiogenic Cargo in Extracellular Vesicles Secreted from Human Adipose Tissue-Derived Stem Cells and Induction of Angiogenesis In Vitro and In Vivo

by Prakash Gangadaran, Ramya Lakshmi Rajendran, Ji Min Oh, Eun Jung Oh, Chae Moon Hong, Ho Yun Chung, Jaetae Lee and Byeong-Cheol Ahn

Pharmaceutics 2021, 13(4), 495; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13040495 - 05 Apr 2021

Cited by 20 | Viewed by 3012

Abstract

Angiogenesis is defined as the generation of new blood vessels or the sprouting of endothelial cells from a pre-existing vascular network. Angiogenesis occurs during the growth and development of an organism, the response of organs or tissues to injury, and during cancer development and progression. The majority of studies on stem-cell-derived extracellular vesicles (EVs) have used cell lines, and have primarily focused on well-known solitary proteins. Here, we isolated stem cells from human adipose tissue (ADSCs), and we isolated EVs from them (ADSC-EVs). The ADSC-EVs were characterised and 20 angiogenic proteins were analysed using an angiogenic antibody array. Furthermore, we analysed the ability of ADSC-EVs to induce angiogenesis in vitro and in vivo. ADSC-EVs were positive for CD81 and negative for GM130, calnexin, and cytochrome-C. ADSC-EVs showed typical EV spherical morphology and were ~200 nm in size. ADSC-EVs were found to contain angiogenic proteins as cargo, among which interleukin 8 (IL-8) was the most abundant, followed by chemokine (C-C motif) ligand 2 (CCL2), a tissue inhibitor of metalloproteinases 1 (TIMP-1), TIMP-2, and vascular endothelial growth factor-D (VEGF-D). ADSC-EVs treatment increased the proliferation, migration, total vessel length, total number of junctions, and junction density of endothelial cells in vitro. The results of an in vivo Matrigel plug assay revealed that ADSC-EVs induced more blood vessels in the Matrigel compared with the control. These results demonstrate that ADSC-EVs contain angiogenic proteins as cargo and promote angiogenesis in vitro and in vivo. Therefore, ADSC-EVs have potential for therapeutic use in ischaemia. Full article

(This article belongs to the Special Issue Biomimetic Nanomedicine for Cancer Therapy and Diagnosis)

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17 pages, 3454 KiB

Open AccessArticle

Extracellular Vesicles Act as Nano-Transporters of Tyrosine Kinase Inhibitors to Revert Iodine Avidity in Thyroid Cancer

by Ramya Lakshmi Rajendran, Sanjita Paudel, Prakash Gangadaran, Ji Min Oh, Eun Jung Oh, Chae Moon Hong, Sangkyu Lee, Ho Yun Chung, Jaetae Lee and Byeong-Cheol Ahn

Pharmaceutics 2021, 13(2), 248; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13020248 - 10 Feb 2021

Cited by 14 | Viewed by 2520

Abstract

A new approach for using extracellular vesicles (EVs) to deliver tyrosine kinase inhibitors (TKIs) to enhance iodine avidity in radioactive iodine-refractory thyroid cancer is needed. We isolated and characterized primary human adipose-derived stem cells (ADSCs) and isolated their EVs. The EVs were characterized by transmission electron microscopy, nanoparticle tracking analysis, and western blotting. A new TKI was loaded into the EVs by incubation (37 °C; 10 min) or sonication (18 cycles; 4 s per cycle) with 2 s intervals and a 2 min ice bath every six cycles. TKI loading was confirmed and measured by mass spectrometry. EV uptake into radioactive iodine-refractory thyroid cancer cells (SW1736 cells) was confirmed by microscopy. We treated the SW1736 cells with vehicle, TKI, or TKI-loaded EVs (sonication TKI-loaded EVs [EVs^TKI(S)]) and examined the expression of iodide-metabolizing proteins and radioiodine uptake in the SW1736 cells. ADSCs cells showed >99% of typical stem cell markers, such as CD90 and CD105. The EVs displayed a round morphology, had an average size of 211.4 ± 3.83 nm, and were positive for CD81 and Alix and negative for cytochrome c. The mass spectrometry results indicate that the sonication method loaded ~4 times more of the TKI than did the incubation method. The EVs^TKI(S) were used for further experiments. Higher expression levels of iodide-metabolizing mRNA and proteins in the EVs^TKI(S)-treated SW1736 cells than in TKI-treated SW1736 cells were confirmed. EVs^TKI(S) treatment enhanced ¹²⁵I uptake in the recipient SW1736 cells compared with free-TKI treatment. This is the first study that demonstrated successful delivery of a TKI to radioactive iodine-refractory thyroid cancer cells using EVs as the delivery vehicle. This approach can revert radioiodine-resistant thyroid cancer cells back to radioiodine-sensitive thyroid cancer cells. Full article

(This article belongs to the Special Issue Biomimetic Nanomedicine for Cancer Therapy and Diagnosis)

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23 pages, 8969 KiB

Open AccessArticle

Bioinspired Composite, pH-Responsive Sodium Deoxycholate Hydrogel and Generation 4.5 Poly(amidoamine) Dendrimer Improves Cancer Treatment Efficacy via Doxorubicin and Resveratrol Co-Delivery

by Tefera Worku Mekonnen, Abegaz Tizazu Andrgie, Haile Fentahun Darge, Yihenew Simegniew Birhan, Endiries Yibru Hanurry, Hsiao-Ying Chou, Juin-Yih Lai, Hsieh-Chih Tsai, Jen Ming Yang and Yen-Hsiang Chang

Pharmaceutics 2020, 12(11), 1069; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics12111069 - 09 Nov 2020

Cited by 10 | Viewed by 2901

Abstract

Maximizing the antitumor efficacy of doxorubicin (DOX) with a new drug delivery strategy is always desired in the field of biomedical science. Because the clinical applications of DOX in the treatment of cancer is limited by the side effects related to the dose. Herein, we report the co-loading of DOX and resveratrol (RESV) using an injectable in situ formed sodium deoxycholate hydrogel (Na-DOC-hyd) at the pH of the tumor extracellular microenvironment. The sequential, controlled, and sustained release of RESV and DOX for synergistic antitumor effects was confirmed by entrapping G4.5-DOX in the RESV-loaded Na-DOC hydrogel (Na-DOC-hyd-RESV). The synergistic antitumor activity of Na-DOC-hyd-RESV+G4.5-DOX was assessed on HeLa cell xenograft tumor in BALB/c nude mice. In the MTT biocompatibility assay, both the G4.5 PAMAM dendrimer and Na-DOC-hyd exhibited negligible cytotoxicity up to the highest dose of 2.0 mg mL⁻¹ in HeLa, MDA-MB-231, and HaCaT cells. The release profiles of DOX and RESV from the Na-DOC-hyd-RESV+G4.5-DOX confirmed the relatively rapid release of RESV (70.43 ± 1.39%), followed by that of DOX (54.58 ± 0.62%) at pH 6.5 in the 7 days of drug release studies. A single intratumoral injection of Na-DOC-hyd-RESV+G4.5-DOX maximally suppressed tumor growth during the 28 days of the treatment period. Na-DOC-hyd-RESV+G4.5-DOX did not cause any histological damage in the major visceral organs. Therefore, this Na-DOC-hydrogel for dual drugs (DOX and RESV) delivery at the pH of the tumor extracellular microenvironment is a promising, safe, and effective combination for antitumor chemotherapy. Full article

(This article belongs to the Special Issue Biomimetic Nanomedicine for Cancer Therapy and Diagnosis)

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15 pages, 3623 KiB

Open AccessArticle

Shear Stress-Dependent Targeting Efficiency Using Self-Assembled Gelatin–Oleic Nanoparticles in a Biomimetic Microfluidic System

by Taehee Kang, Chulhun Park, Nileshkumar Meghani, Thao T.D. Tran, Phuong H.L. Tran and Beom-Jin Lee

Pharmaceutics 2020, 12(6), 555; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics12060555 - 16 Jun 2020

Cited by 17 | Viewed by 2569

Abstract

Cellular properties and microenvironments, as well as the characteristics of nanoparticles (NPs), affect the cellular uptake and cytotoxic effects of drug-loaded NPs. Since there is fluid flow in the human blood system, fluid flow also affects the drug delivery efficiency of NPs. This study aimed to evaluate the cellular behaviors of drug-loaded soft NPs on A549 cancer cells under different levels of shear stress (0.5, 5, and 50 dynes/cm²) in the biomimetic microfluidic system. The soft self-assembled NPs were formed by the gelatin–oleic conjugate (GOC). The poorly water-soluble coumarin-6 or paclitaxel (PTX) were used as model markers for encapsulation within self-assembled NPs (C-GONs or PTX-GONs, respectively). The cellular uptake of C-GONs was found to be improved with shear-stress dependence. The inhibitory concentration (IC₅₀) of PTX-GONs at 0.5, 5, and 50 dynes/cm² was 0.106 µg/mL, 0.108 µg/mL, and 0.091 µg/mL, respectively, as compared to 0.138 µg/mL in a static condition. The cell killing efficiency of PTX-GONs was increased in the highest shear stress of 50 dynes/cm² in the static condition, and other levels of shear stress in dynamic conditions. Full article

(This article belongs to the Special Issue Biomimetic Nanomedicine for Cancer Therapy and Diagnosis)

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