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Pharmaceutics
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Natural Nanoparticle for Cancer Diagnosis and Treatment
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Natural Nanoparticle for Cancer Diagnosis and Treatment

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

Deadline for manuscript submissions: closed (28 February 2022) | Viewed by 35425

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editor

Dr. Serena Mazzucchelli

E-Mail Website
Guest Editor
Department of Biomedical and Clinical Sciences, Università degli Studi di Milano, Via G. B. Grassi 74, 20157 Milan, Italy
Interests: nano-oncology; nano-drug delivery; protein nanocages; breast cancer; nano-tracers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In the last twenty years, nanoparticles have been extensively studied as carrier for cancer imaging and drug delivery, since they are useful to improve bioavailability, tissue penetration, and circulation time of their cargo molecules. However, nanoparticle toxicity, immunogenicity, and sequestration by macrophages are issues that strongly limit their clinical translation. In this scenario, natural nanoparticles, such as exosomes and protein or DNA nanocages represent a charming alternative to synthetic metal or polymeric nanoparticles, thanks to their safety, biocompatibility, and biodegradability due to their biological nature. Their production and manipulation take place in mild conditions, preserving drug or probe functionality. Moreover, they generally display high stability in the physiological environment, allowing researchers to avoid common problems related to nanoparticle aggregation. They could also be modified by inserting surface functionalities to affect stability, surface charge, and ligand display, in order to maximize their bioavailability, tumor targeting, and tissue penetration. Moreover, natural nanoparticles are generally arranged to form a shell that displays three regions of interfaces, allowing researchers to realize multifunctional nanoparticles by combining nano-probes for imaging with drug delivery devices. These features are strongly appealing in order to face cancer, where the development of tumor-targeted specific devices could be useful to improve patient compliance. 

This Special Issue serves to depict the current landscape of natural nanoparticles developed to improve cancer management and we invite articles able to better highlight any feature about natural nanoparticles exploited for cancer.

Dr. Mazzucchelli Serena
Guest Editor

Manuscript Submission Information

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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

  • natural nanoparticles
  • drug delivery
  • tumor-targeting probes

Related Special Issue

Published Papers (11 papers)

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Editorial

Jump to: Research, Review

2 pages, 190 KiB  
Editorial
Natural Nanoparticles: A Safe Bullet for Treatment and Detection of Solid Tumors
by Serena Mazzucchelli
Pharmaceutics 2022, 14(6), 1126; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14061126 - 25 May 2022
Viewed by 1090
Abstract
In the last couple of decades, nanoparticles have been extensively studied as carriers for cancer imaging agents and as drug delivery platforms, due to their ability to positively affect the distribution and tumor-targeting properties of delivered compounds [...] Full article
(This article belongs to the Special Issue Natural Nanoparticle for Cancer Diagnosis and Treatment)

Research

Jump to: Editorial, Review

15 pages, 1652 KiB  
Article
Preparation and In Vitro-In Vivo Evaluation of Luteolin Loaded Gastroretentive Microsponge for the Eradication of Helicobacter pylori Infections
by Mohammed Jafar, Mohammed Salahuddin, Mohd Sajjad Ahmad Khan, Yasir Alshehry, Nazar Radwan Alrwaili, Yazeed Ali Alzahrani, Syed Sarim Imam and Sultan Alshehri
Pharmaceutics 2021, 13(12), 2094; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13122094 - 06 Dec 2021
Cited by 16 | Viewed by 3406
Abstract
The current study aimed to develop a luteolin gastric floating microsponge for targeting Helicobacter pylori. The microsponge formulations were prepared by a quasi-emulsion method, and then evaluated for various physicochemical variables. The best microsponge was further assessed for drug-polymer interactions, surface morphology, [...] Read more.
The current study aimed to develop a luteolin gastric floating microsponge for targeting Helicobacter pylori. The microsponge formulations were prepared by a quasi-emulsion method, and then evaluated for various physicochemical variables. The best microsponge was further assessed for drug-polymer interactions, surface morphology, in vivo floating, and in vitro anti H. pylori activity. The formulation which exhibited comparatively good production yield (64.45% ± 0.83), high entrapment efficiency (67.33% ± 3.79), prolonged in vitro floating time (>8 h), and sustained in-vitro drug release was selected as the best microsponge. The SEM study revealed that the best microsponge was spherical in shape and has a porous surface with interconnecting channels. DSC and XRD studies demonstrated the dispersion of luteolin in the polymeric matrix of the microsponge. Ultrasonography confirmed that the best microsponge could in the rat stomach for 4 h. The in vitro MIC results indicate that the anti H. pylori activity of the best microsponge was almost doubled and more sustained compared to pure luteolin. To conclude, it can be said that the developed luteolin gastric floating microsponge could be a better option to effectively eradicate H. pylori infections and the histopathological and pharmacodynamic assessments of our best microsponge can be expected to provide a rewarding outcome. Full article
(This article belongs to the Special Issue Natural Nanoparticle for Cancer Diagnosis and Treatment)
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13 pages, 21497 KiB  
Article
Fucoidan-Based Nanoparticles with Inherently Therapeutic Efficacy for Cancer Treatment
by Chih-Sheng Chiang, Bo-Jie Huang, Jui-Yu Chen, Wee Wei Chieng, Seh Hong Lim, Wei Lee, Weoi-Cherng Shyu and Long-Bin Jeng
Pharmaceutics 2021, 13(12), 1986; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13121986 - 23 Nov 2021
Cited by 9 | Viewed by 2669
Abstract
The anticancer properties of fucoidan have been widely studied in cancer research. However, the lack of safety information on the parenteral administration of fucoidan and its rapid clearance from the system have limited its application. Herein, we assessed the therapeutic efficacy and safety [...] Read more.
The anticancer properties of fucoidan have been widely studied in cancer research. However, the lack of safety information on the parenteral administration of fucoidan and its rapid clearance from the system have limited its application. Herein, we assessed the therapeutic efficacy and safety of fucoidan and developed fucoidan nanoparticles (FuNPs) to enhance their therapeutic effect in the mouse model of breast cancer. FuNPs were synthesized through the emulsion method, and the stable colloid has an average size of 216.3 nm. FuNPs were efficiently internalized into breast cancer cells in vitro, demonstrating an enhanced antitumor activity in comparison with free form fucoidan. After the treatment of FuNPs, the tumor progression was significantly inhibited in viv. The tumor volume was reduced by 2.49-fold compared with the control group. Moreover, the inhibition of the invasion of tumor cells into the lungs revealed the antimetastatic properties of the FuNPs. FuNPs, as naturally marine polysaccharide-based nanoparticles, have shown their broader therapeutic window and enhanced antimetastatic ability, opening an avenue to the development of the inherently therapeutic nanomedicines. Full article
(This article belongs to the Special Issue Natural Nanoparticle for Cancer Diagnosis and Treatment)
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17 pages, 3680 KiB  
Article
Formulation, Optimization and Evaluation of Luteolin-Loaded Topical Nanoparticulate Delivery System for the Skin Cancer
by Imran Kazmi, Fahad A. Al-Abbasi, Muhammad Shahid Nadeem, Hisham N. Altayb, Sultan Alshehri and Syed Sarim Imam
Pharmaceutics 2021, 13(11), 1749; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13111749 - 20 Oct 2021
Cited by 15 | Viewed by 2265
Abstract
In the present study, luteolin (LT)-loaded nanosized vesicles (LT-NVs) were prepared by a solvent evaporation–hydration method using phospholipid and edge activator. The formulation was optimized using three factors at a three-level Box–Behnken design. The formulated LT-NVs were prepared using the three independent variables [...] Read more.
In the present study, luteolin (LT)-loaded nanosized vesicles (LT-NVs) were prepared by a solvent evaporation–hydration method using phospholipid and edge activator. The formulation was optimized using three factors at a three-level Box–Behnken design. The formulated LT-NVs were prepared using the three independent variables phospholipid (A), edge activator (B) and sonication time (C). The effect of used variables was assessed on the vesicle size (Y1) and encapsulation efficiency (Y2). The selection of optimum composition (LT-NVopt) was based on the point prediction method of the software. The prepared LT-NVopt showed the particle size of 189.92 ± 3.25 nm with an encapsulation efficiency of 92.43 ± 4.12% with PDI and zeta potential value of 0.32 and −21 mV, respectively. The formulation LT-NVopt was further converted into Carbopol 934 gel (1% w/v) to enhance skin retention. LT-NVoptG was further characterized for viscosity, spreadability, drug content, drug release, drug permeation and antioxidant, antimicrobial and cytotoxicity assessment. The evaluation result revealed optimum pH, viscosity, spreadability and good drug content. There was enhanced LT release (60.81 ± 2.87%), as well as LT permeation (128.21 ± 3.56 µg/cm2/h), which was found in comparison to the pure LT. The antioxidant and antimicrobial study results revealed significantly (p ˂ 0.05) better antioxidant potential and antimicrobial activity against the tested organisms. Finally, the samples were evaluated for cytotoxicity assessment using skin cancer cell line and results revealed a significant difference in the viability % at the tested concentration. LT-NVoptG showed a significantly lower IC50 value than the pure LT. From the study, it can be concluded that the prepared LT-NVoptG was found to be an alternative to the synthetic drug as well as conventional delivery systems. Full article
(This article belongs to the Special Issue Natural Nanoparticle for Cancer Diagnosis and Treatment)
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12 pages, 3506 KiB  
Article
M1 Macrophage-Derived Exosomes Loaded with Gemcitabine and Deferasirox against Chemoresistant Pancreatic Cancer
by Yongmei Zhao, Yuanlin Zheng, Yan Zhu, Yi Zhang, Hongyan Zhu and Tianqing Liu
Pharmaceutics 2021, 13(9), 1493; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13091493 - 17 Sep 2021
Cited by 45 | Viewed by 3850
Abstract
Pancreatic cancer is a malignant disease with high mortality and poor prognosis due to lack of early diagnosis and low treatment efficiency after diagnosis. Although Gemcitabine (GEM) is used as the first-line chemotherapeutic drug, chemoresistance is still the major problem that limits its [...] Read more.
Pancreatic cancer is a malignant disease with high mortality and poor prognosis due to lack of early diagnosis and low treatment efficiency after diagnosis. Although Gemcitabine (GEM) is used as the first-line chemotherapeutic drug, chemoresistance is still the major problem that limits its therapeutic efficacy. Here in this study, we developed a specific M1 macrophage-derived exosome (M1Exo)-based drug delivery system against GEM resistance in pancreatic cancer. In addition to GEM, Deferasirox (DFX) was also loaded into drug carrier, M1Exo, in order to inhibit ribonucleotide reductase regulatory subunit M2 (RRM2) expression via depleting iron, and thus increase chemosensitivity of GEM. The M1Exo nanoformulations combining both GEM and DFX significantly enhanced the therapeutic efficacy on the GEM-resistant PANC-1/GEM cells and 3D tumor spheroids by inhibiting cancer cell proliferation, cell attachment and migration, and chemoresistance to GEM. These data demonstrated that M1Exo loaded with GEM and DFX offered an efficient therapeutic strategy for drug-resistant pancreatic cancer. Full article
(This article belongs to the Special Issue Natural Nanoparticle for Cancer Diagnosis and Treatment)
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Review

Jump to: Editorial, Research

28 pages, 5512 KiB  
Review
An Up-to-Date Review of Natural Nanoparticles for Cancer Management
by Daniel Ion, Adelina-Gabriela Niculescu, Dan Nicolae Păduraru, Octavian Andronic, Florentina Mușat, Alexandru Mihai Grumezescu and Alexandra Bolocan
Pharmaceutics 2022, 14(1), 18; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14010018 - 22 Dec 2021
Cited by 24 | Viewed by 3863
Abstract
Cancer represents one of the leading causes of morbidity and mortality worldwide, imposing an urgent need to develop more efficient treatment alternatives. In this respect, much attention has been drawn from conventional cancer treatments to more modern approaches, such as the use of [...] Read more.
Cancer represents one of the leading causes of morbidity and mortality worldwide, imposing an urgent need to develop more efficient treatment alternatives. In this respect, much attention has been drawn from conventional cancer treatments to more modern approaches, such as the use of nanotechnology. Extensive research has been done for designing innovative nanoparticles able to specifically target tumor cells and ensure the controlled release of anticancer agents. To avoid the potential toxicity of synthetic materials, natural nanoparticles started to attract increasing scientific interest. In this context, this paper aims to review the most important natural nanoparticles used as active ingredients (e.g., polyphenols, polysaccharides, proteins, and sterol-like compounds) or as carriers (e.g., proteins, polysaccharides, viral nanoparticles, and exosomes) of various anticancer moieties, focusing on their recent applications in treating diverse malignancies. Full article
(This article belongs to the Special Issue Natural Nanoparticle for Cancer Diagnosis and Treatment)
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19 pages, 2300 KiB  
Review
Protein-Based Nanoparticles for the Imaging and Treatment of Solid Tumors: The Case of Ferritin Nanocages, a Narrative Review
by Francesco Mainini, Arianna Bonizzi, Marta Sevieri, Leopoldo Sitia, Marta Truffi, Fabio Corsi and Serena Mazzucchelli
Pharmaceutics 2021, 13(12), 2000; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13122000 - 25 Nov 2021
Cited by 14 | Viewed by 2837
Abstract
Protein nanocages have been studied extensively, due to their unique architecture, exceptional biocompatibility and highly customization capabilities. In particular, ferritin nanocages (FNs) have been employed for the delivery of a vast array of molecules, ranging from chemotherapeutics to imaging agents, among others. One [...] Read more.
Protein nanocages have been studied extensively, due to their unique architecture, exceptional biocompatibility and highly customization capabilities. In particular, ferritin nanocages (FNs) have been employed for the delivery of a vast array of molecules, ranging from chemotherapeutics to imaging agents, among others. One of the main favorable characteristics of FNs is their intrinsic targeting efficiency toward the Transferrin Receptor 1, which is overexpressed in many tumors. Furthermore, genetic manipulation can be employed to introduce novel variants that are able to improve the loading capacity, targeting capabilities and bio-availability of this versatile drug delivery system. In this review, we discuss the main characteristics of FN and the most recent applications of this promising nanotechnology in the field of oncology with a particular emphasis on the imaging and treatment of solid tumors. Full article
(This article belongs to the Special Issue Natural Nanoparticle for Cancer Diagnosis and Treatment)
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21 pages, 1855 KiB  
Review
Nanoformulations of α-Mangostin for Cancer Drug Delivery System
by Lisna Meylina, Muchtaridi Muchtaridi, I Made Joni, Ahmed Fouad Abdelwahab Mohammed and Nasrul Wathoni
Pharmaceutics 2021, 13(12), 1993; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13121993 - 24 Nov 2021
Cited by 18 | Viewed by 3362
Abstract
Natural compounds are emerging as effective agents for the treatment of malignant diseases. The active constituent of α-mangostin from the pericarp of Garcinia mangostana L. has earned significant interest as a plant base compound with anticancer properties. Despite α-mangostin’s superior properties as an [...] Read more.
Natural compounds are emerging as effective agents for the treatment of malignant diseases. The active constituent of α-mangostin from the pericarp of Garcinia mangostana L. has earned significant interest as a plant base compound with anticancer properties. Despite α-mangostin’s superior properties as an anticancer agent, its applications are limited due to its poor solubility and physicochemical stability, rapid systemic clearance, and low cellular uptake. Our review aimed to summarize and discuss the nanoparticle formulations of α-mangostin for cancer drug delivery systems from published papers recorded in Scopus, PubMed, and Google Scholar. We investigated various types of α-mangostin nanoformulations to improve its anticancer efficacy by improving bioavailability, cellular uptake, and localization to specific areas These nanoformulations include nanofibers, lipid carrier nanostructures, solid lipid nanoparticles, polymeric nanoparticles, nanomicelles, liposomes, and gold nanoparticles. Notably, polymeric nanoparticles and nanomicelles can increase the accumulation of α-mangostin into tumors and inhibit tumor growth in vivo. In addition, polymeric nanoparticles with the addition of target ligands can increase the cellular uptake of α-mangostin. In conclusion, nanoformulations of α-mangostin are a promising tool to enhance the cellular uptake, accumulation in cancer cells, and the efficacy of α-mangostin as a candidate for anticancer drugs. Full article
(This article belongs to the Special Issue Natural Nanoparticle for Cancer Diagnosis and Treatment)
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32 pages, 6228 KiB  
Review
Natural Carbon Nanodots: Toxicity Assessment and Theranostic Biological Application
by Ming-Hsien Chan, Bo-Gu Chen, Loan Thi Ngo, Wen-Tse Huang, Chien-Hsiu Li, Ru-Shi Liu and Michael Hsiao
Pharmaceutics 2021, 13(11), 1874; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13111874 - 05 Nov 2021
Cited by 28 | Viewed by 3475
Abstract
This review outlines the methods for preparing carbon dots (CDs) from various natural resources to select the process to produce CDs with the best biological application efficacy. The oxidative activity of CDs mainly involves photo-induced cell damage and the destruction of biofilm matrices [...] Read more.
This review outlines the methods for preparing carbon dots (CDs) from various natural resources to select the process to produce CDs with the best biological application efficacy. The oxidative activity of CDs mainly involves photo-induced cell damage and the destruction of biofilm matrices through the production of reactive oxygen species (ROS), thereby causing cell auto-apoptosis. Recent research has found that CDs derived from organic carbon sources can treat cancer cells as effectively as conventional drugs without causing damage to normal cells. CDs obtained by heating a natural carbon source inherit properties similar to the carbon source from which they are derived. Importantly, these characteristics can be exploited to perform non-invasive targeted therapy on human cancers, avoiding the harm caused to the human body by conventional treatments. CDs are attractive for large-scale clinical applications. Water, herbs, plants, and probiotics are ideal carbon-containing sources that can be used to synthesize therapeutic and diagnostic CDs that have become the focus of attention due to their excellent light stability, fluorescence, good biocompatibility, and low toxicity. They can be applied as biosensors, bioimaging, diagnosis, and treatment applications. These advantages make CDs attractive for large-scale clinical application, providing new technologies and methods for disease occurrence, diagnosis, and treatment research. Full article
(This article belongs to the Special Issue Natural Nanoparticle for Cancer Diagnosis and Treatment)
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23 pages, 1444 KiB  
Review
RNAi-Based Approaches for Pancreatic Cancer Therapy
by Min Ju Kim, Hyeyoun Chang, Gihoon Nam, Youngji Ko, Sun Hwa Kim, Thomas M. Roberts and Ju Hee Ryu
Pharmaceutics 2021, 13(10), 1638; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13101638 - 08 Oct 2021
Cited by 12 | Viewed by 3156
Abstract
Pancreatic cancer is one of the most lethal forms of cancer, predicted to be the second leading cause of cancer-associated death by 2025. Despite intensive research for effective treatment strategies and novel anticancer drugs over the past decade, the overall patient survival rate [...] Read more.
Pancreatic cancer is one of the most lethal forms of cancer, predicted to be the second leading cause of cancer-associated death by 2025. Despite intensive research for effective treatment strategies and novel anticancer drugs over the past decade, the overall patient survival rate remains low. RNA interference (RNAi) is capable of interfering with expression of specific genes and has emerged as a promising approach for pancreatic cancer because genetic aberrations and dysregulated signaling are the drivers for tumor formation and the stromal barrier to conventional therapy. Despite its therapeutic potential, RNA-based drugs have remaining hurdles such as poor tumor delivery and susceptibility to serum degradation, which could be overcome with the incorporation of nanocarriers for clinical applications. Here we summarize the use of small interfering RNA (siRNA) and microRNA (miRNA) in pancreatic cancer therapy in preclinical reports with approaches for targeting either the tumor or tumor microenvironment (TME) using various types of nanocarriers. In these studies, inhibition of oncogene expression and induction of a tumor suppressive response in cancer cells and surrounding immune cells in TME exhibited a strong anticancer effect in pancreatic cancer models. The review discusses the remaining challenges and prospective strategies suggesting the potential of RNAi-based therapeutics for pancreatic cancer. Full article
(This article belongs to the Special Issue Natural Nanoparticle for Cancer Diagnosis and Treatment)
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25 pages, 5858 KiB  
Review
Biomimetic Bacterial Membrane Vesicles for Drug Delivery Applications
by Sajid Fazal and Ruda Lee
Pharmaceutics 2021, 13(9), 1430; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13091430 - 09 Sep 2021
Cited by 22 | Viewed by 3982
Abstract
Numerous factors need to be considered to develop a nanodrug delivery system that is biocompatible, non-toxic, easy to synthesize, cost-effective, and feasible for scale up over and above their therapeutic efficacy. With regards to this, worldwide, exosomes, which are nano-sized vesicles obtained from [...] Read more.
Numerous factors need to be considered to develop a nanodrug delivery system that is biocompatible, non-toxic, easy to synthesize, cost-effective, and feasible for scale up over and above their therapeutic efficacy. With regards to this, worldwide, exosomes, which are nano-sized vesicles obtained from mammalian cells, are being explored as a biomimetic drug delivery system that has superior biocompatibility and high translational capability. However, the economics of undertaking large-scale mammalian culture to derive exosomal vesicles for translation seems to be challenging and unfeasible. Recently, Bacterial Membrane Vesicles (BMVs) derived from bacteria are being explored as a viable alternative as biomimetic drug delivery systems that can be manufactured relatively easily at much lower costs at a large scale. Until now, BMVs have been investigated extensively as successful immunomodulating agents, but their capability as drug delivery systems remains to be explored in detail. In this review, the use of BMVs as suitable cargo delivery vehicles is discussed with focus on their use for in vivo treatment of cancer and bacterial infections reported thus far. Additionally, the different types of BMVs, factors affecting their synthesis and different cargo loading techniques used in BMVs are also discussed. Full article
(This article belongs to the Special Issue Natural Nanoparticle for Cancer Diagnosis and Treatment)
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