Nanoparticle Delivery to Tumors: Challenges and Advances

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

Deadline for manuscript submissions: closed (31 July 2023) | Viewed by 31478

Special Issue Editors


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Guest Editor
Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Interests: cellular and molecular imaging; nanoparticle delivery; radiopharmaceuticals

E-Mail Website
Guest Editor
Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Interests: cellular and molecular imaging; drug and nanoparticle delivery; biomaterials; cell-based therapies

Special Issue Information

Dear Colleagues,

Nanoparticles have emerged as versatile drug delivery vehicles for applications in oncology and other pathologies. However, although several types of nanoparticles have been developed, their effective delivery to tumors is still a major challenge, especially nanoparticles ≥100 nm in diameter. Enhanced vascular permeability in tumors has been shown to play an essential role in the delivery of nanoparticles of this diameter range to tumors, through the enhanced permeability and retention (EPR) effect. Furthermore, the poor clinical performance of some nanoparticles has been partially attributed to variabilities in the vascular permeability within tumors and within different patient populations. Consequently, tumor-priming strategies designed specifically to enhance tumor vascular permeability and subsequently increase the delivery of nanoparticles to tumors are currently being explored. Imaging techniques to monitor the efficiency of these tumor-priming strategies are also being developed. In this Special Issue, we shall cover some of the challenges associated with delivering nanoparticles to tumors, and some advances that have been made to increase the delivery efficiency of nanoparticles to tumors.

Dr. Sangeeta Ray
Dr. Ethel J. Ngen
Guest Editors

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Keywords

  • nanoparticle delivery
  • image-guided nanoparticle delivery
  • enhanced permeability and retention effect (EPR effect)
  • tumor re-engineering
  • re-engineering tumor vascular permeability

Published Papers (12 papers)

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Research

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15 pages, 3770 KiB  
Article
Theranostic Cancer Treatment Using Lentinan-Coated Selenium Nanoparticles and Label-Free CEST MRI
by Guanfu Liu, Jiabao Ling, Lizhen He, Yuan Xu, Tianfeng Chen, Changzheng Shi and Liangping Luo
Pharmaceutics 2023, 15(1), 120; https://doi.org/10.3390/pharmaceutics15010120 - 29 Dec 2022
Cited by 1 | Viewed by 1817
Abstract
Selenium nanoparticle (SeNP)-based nanotherapeutics have become an emerging cancer therapy, while effective drug delivery remains a technical hurdle. A theranostic approach, through which imaging companions are integrated with SeNPs, will allow image-guided drug delivery and, therefore, is highly desirable. Traditional methods require the [...] Read more.
Selenium nanoparticle (SeNP)-based nanotherapeutics have become an emerging cancer therapy, while effective drug delivery remains a technical hurdle. A theranostic approach, through which imaging companions are integrated with SeNPs, will allow image-guided drug delivery and, therefore, is highly desirable. Traditional methods require the chemical conjugation of imaging agents to the surface of nanoparticles, which may impede the later clinical translation. In this study, we developed a label-free strategy in which lentinan-functionalized SeNPs (LNT-SeNPs) are detected using MRI by the hydroxyl protons carried on LNT molecules. The in vitro phantom study showed that LNT and LNT-SeNPs have a strong CEST signal at 1.0 ppm apart from the water resonance, suggesting an in vivo detectability in the µM concentration range. Demonstrated on CT26 colon tumor cells, LNT-SeNPs exert a strong anticancer effect (IC50 = 4.8 μM), prominently attributed to the ability to generate intracellular reactive oxygen species. However, when testing in a mouse model of CT26 tumors, administration of LNT-SeNPs alone was found unable to deliver sufficient drugs to the tumor, leading to poor treatment responses. To improve the drug delivery, we co-injected LNT-SeNPs and TNF-α, a previously reported drug that could effectively damage the endothelial cells in the tumor vasculature, thereby increasing drug delivery to the tumor. Our results revealed a 75% increase in the intratumoral CEST MRI signal, indicating a markedly increased delivery efficiency of LNT-SeNPs when combined with TNF-α. The combination therapy also resulted in a significantly enhanced treatment outcome, as revealed by the tumor growth study. Taken together, our study demonstrates the first label-free, SeNP-based theranostic system, in which LNT was used for both functional surface coating and CEST MRI signal generating. Such a theranostic LNT-SeNP system is advantageous because it requires chemical labeling and, therefore, has high biocompatibility and low translatable barriers. Full article
(This article belongs to the Special Issue Nanoparticle Delivery to Tumors: Challenges and Advances)
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19 pages, 3869 KiB  
Article
Label-Free Assessment of Mannitol Accumulation Following Osmotic Blood–Brain Barrier Opening Using Chemical Exchange Saturation Transfer Magnetic Resonance Imaging
by Jing Liu, Chengyan Chu, Jia Zhang, Chongxue Bie, Lin Chen, Safiya Aafreen, Jiadi Xu, David O. Kamson, Peter C. M. van Zijl, Piotr Walczak, Miroslaw Janowski and Guanshu Liu
Pharmaceutics 2022, 14(11), 2529; https://doi.org/10.3390/pharmaceutics14112529 - 20 Nov 2022
Cited by 6 | Viewed by 2272
Abstract
Purpose: Mannitol is a hyperosmolar agent for reducing intracranial pressure and inducing osmotic blood–brain barrier opening (OBBBO). There is a great clinical need for a non-invasive method to optimize the safety of mannitol dosing. The aim of this study was to develop a [...] Read more.
Purpose: Mannitol is a hyperosmolar agent for reducing intracranial pressure and inducing osmotic blood–brain barrier opening (OBBBO). There is a great clinical need for a non-invasive method to optimize the safety of mannitol dosing. The aim of this study was to develop a label-free Chemical Exchange Saturation Transfer (CEST)-based MRI approach for detecting intracranial accumulation of mannitol following OBBBO. Methods: In vitro MRI was conducted to measure the CEST properties of D-mannitol of different concentrations and pH. In vivo MRI and MRS measurements were conducted on Sprague-Dawley rats using a Biospec 11.7T horizontal MRI scanner. Rats were catheterized at the internal carotid artery (ICA) and randomly grouped to receive either 1 mL or 3 mL D-mannitol. CEST MR images were acquired before and at 20 min after the infusion. Results: In vitro MRI showed that mannitol has a strong, broad CEST contrast at around 0.8 ppm with a mM CEST MRI detectability. In vivo studies showed that CEST MRI could effectively detect mannitol in the brain. The low dose mannitol treatment led to OBBBO but no significant mannitol accumulation, whereas the high dose regimen resulted in both OBBBO and mannitol accumulation. The CEST MRI findings were consistent with 1H-MRS and Gd-enhanced MRI assessments. Conclusion: We demonstrated that CEST MRI can be used for non-invasive, label-free detection of mannitol accumulation in the brain following BBBO treatment. This method may be useful as a rapid imaging tool to optimize the dosing of mannitol-based OBBBO and improve its safety and efficacy. Full article
(This article belongs to the Special Issue Nanoparticle Delivery to Tumors: Challenges and Advances)
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14 pages, 2972 KiB  
Article
Laminin Receptor-Mediated Nanoparticle Uptake by Tumor Cells: Interplay of Epigallocatechin Gallate and Magnetic Force at Nano–Bio Interface
by Sheng-Chieh Hsu, Nian-Ping Wu, Yi-Ching Lu and Yunn-Hwa Ma
Pharmaceutics 2022, 14(8), 1523; https://doi.org/10.3390/pharmaceutics14081523 - 22 Jul 2022
Cited by 2 | Viewed by 2083
Abstract
Epigallocatechin gallate (EGCG), a major tea catechin, enhances cellular uptake of magnetic nanoparticles (MNPs), but the mechanism remains unclear. Since EGCG may interact with the 67-kDa laminin receptor (67LR) and epidermal growth factor receptor (EGFR), we investigate whether a receptor and its downstream [...] Read more.
Epigallocatechin gallate (EGCG), a major tea catechin, enhances cellular uptake of magnetic nanoparticles (MNPs), but the mechanism remains unclear. Since EGCG may interact with the 67-kDa laminin receptor (67LR) and epidermal growth factor receptor (EGFR), we investigate whether a receptor and its downstream signaling may mediate EGCG’s enhancement effects on nanoparticle uptake. As measured using a colorimetric iron assay, EGCG induced a concentration-dependent enhancement effect of MNP internalization by LN-229 glioma cells, which was synergistically enhanced by the application of a magnetic field. Transmission electron microscopy demonstrated that EGCG increased the number, but not the size, of internalized vesicles, whereas EGCG and the magnet synergistically increased the size of vesicles. EGCG appears to enhance particle–particle interaction and thus aggregation following a 5-min magnet application. An antibody against 67LR, knockdown of 67LR, and a 67LR peptide (amino acid 161–170 of 67LR) attenuated EGCG-induced MNP uptake by 35%, 100%, and 45%, respectively, suggesting a crucial role of 67LR in the effects of EGCG. Heparin, the 67LR-binding glycosaminoglycan, attenuated EGCG-induced MNP uptake in the absence, but not presence, of the magnet. Such enhancement effects of EGCG were attenuated by LY294002 (a phosphoinositide 3-kinase inhibitor) and Akt inhibitor, but not by agents affecting cGMP levels, suggesting potential involvement of signaling downstream of 67LR. In contrast, the antibody against EGFR exerted no effect on EGCG-enhanced internalization. These results suggest that 67LR may be potentially amenable to tumor-targeted therapeutics. Full article
(This article belongs to the Special Issue Nanoparticle Delivery to Tumors: Challenges and Advances)
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15 pages, 2309 KiB  
Article
VEGF Overexpression Significantly Increases Nanoparticle-Mediated siRNA Delivery and Target-Gene Downregulation
by Shanshan Tan, Zhihang Chen, Yelena Mironchik, Noriko Mori, Marie-France Penet, Ge Si, Balaji Krishnamachary and Zaver M. Bhujwalla
Pharmaceutics 2022, 14(6), 1260; https://doi.org/10.3390/pharmaceutics14061260 - 14 Jun 2022
Cited by 4 | Viewed by 2039
Abstract
The availability of nanoparticles (NPs) to deliver small interfering RNA (siRNA) has significantly expanded the specificity and range of ‘druggable’ targets for precision medicine in cancer. This is especially important for cancers such as triple negative breast cancer (TNBC) for which there are [...] Read more.
The availability of nanoparticles (NPs) to deliver small interfering RNA (siRNA) has significantly expanded the specificity and range of ‘druggable’ targets for precision medicine in cancer. This is especially important for cancers such as triple negative breast cancer (TNBC) for which there are no targeted treatments. Our purpose here was to understand the role of tumor vasculature and vascular endothelial growth factor (VEGF) overexpression in a TNBC xenograft in improving the delivery and function of siRNA NPs using in vivo as well as ex vivo imaging. We used triple negative MDA-MB-231 human breast cancer xenografts derived from cells engineered to overexpress VEGF to understand the role of VEGF and vascularization in NP delivery and function. We used polyethylene glycol (PEG) conjugated polyethylenimine (PEI) NPs to deliver siRNA that downregulates choline kinase alpha (Chkα), an enzyme that is associated with malignant transformation and tumor progression. Because Chkα converts choline to phosphocholine, effective delivery of Chkα siRNA NPs resulted in functional changes of a significant decrease in phosphocholine and total choline that was detected with 1H magnetic resonance spectroscopy (MRS). We observed a significant increase in NP delivery and a significant decrease in Chkα and phosphocholine in VEGF overexpressing xenografts. Our results demonstrated the importance of tumor vascularization in achieving effective siRNA delivery and downregulation of the target gene Chkα and its function. Full article
(This article belongs to the Special Issue Nanoparticle Delivery to Tumors: Challenges and Advances)
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13 pages, 2212 KiB  
Article
Image-Based Quantification of Gold Nanoparticle Uptake and Localization in 3D Tumor Models to Inform Radiosensitization Schedule
by Ljubica Z. Petrovic, Michael Oumano, Justin Hanlon, Mark Arnoldussen, Igor Koruga, Sayeda Yasmin-Karim, Wilfred Ngwa and Jonathan Celli
Pharmaceutics 2022, 14(3), 667; https://doi.org/10.3390/pharmaceutics14030667 - 18 Mar 2022
Cited by 2 | Viewed by 2165
Abstract
Gold nanoparticles (GNPs) have shown particular promise as radiosensitizing agents and as complementary drug delivery agents to improve therapeutic index in cancer treatment. Optimal implementation, however, depends critically on the localization of GNPs at the time of irradiation, which, in turn, depends on [...] Read more.
Gold nanoparticles (GNPs) have shown particular promise as radiosensitizing agents and as complementary drug delivery agents to improve therapeutic index in cancer treatment. Optimal implementation, however, depends critically on the localization of GNPs at the time of irradiation, which, in turn, depends on their size, shape, and chemical functionalization, as well as organism-level pharmacokinetics and interactions with the tumor microenvironment. Here, we use in vitro 3D cultures of A549 lung carcinoma cells, which recapitulate interaction with extracellular matrix (ECM) components, combined with quantitative fluorescence imaging to study how time-dependent localization of ultrasmall GNPs in tumors and ECM impacts the degree of damage enhancement to tumor cells. Confocal imaging of fluorescence-labeled GNPs in 3D culture reveals that nanoparticles are initially embedded in ECM and only gradually accumulate in cancer cells over multiple days. Furthermore, the timing of GNP redistribution from ECM to cellular compartments directly impacts efficacy, with major damage enhancement when irradiation is performed after GNPs have accumulated significantly in 3D tumor nodules. These results underscore the importance of the timing and scheduling in treatment planning to ensure optimal radiosensitization, as well as the necessity of studying these effects in model systems that recapitulate elements of tumor microenvironment interaction. Full article
(This article belongs to the Special Issue Nanoparticle Delivery to Tumors: Challenges and Advances)
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14 pages, 1665 KiB  
Article
An Evaluation of CXCR4 Targeting with PAMAM Dendrimer Conjugates for Oncologic Applications
by Wojciech G. Lesniak, Babak Behnam Azad, Samit Chatterjee, Ala Lisok and Martin G. Pomper
Pharmaceutics 2022, 14(3), 655; https://doi.org/10.3390/pharmaceutics14030655 - 16 Mar 2022
Cited by 4 | Viewed by 2563
Abstract
The chemokine receptor 4 (CXCR4) is a promising diagnostic and therapeutic target for the management of various cancers. CXCR4 has been utilized in immunotherapy, targeted drug delivery, and endoradiotherapy. Poly(amidoamine) [PAMAM] dendrimers are well-defined polymers with unique properties that have been used in [...] Read more.
The chemokine receptor 4 (CXCR4) is a promising diagnostic and therapeutic target for the management of various cancers. CXCR4 has been utilized in immunotherapy, targeted drug delivery, and endoradiotherapy. Poly(amidoamine) [PAMAM] dendrimers are well-defined polymers with unique properties that have been used in the fabrication of nanomaterials for several biomedical applications. Here, we describe the formulation and pharmacokinetics of generation-5 CXCR4-targeted PAMAM (G5-X4) dendrimers. G5-X4 demonstrated an IC50 of 0.95 nM to CXCR4 against CXCL12-Red in CHO-SNAP-CXCR4 cells. Single-photon computed tomography/computed tomography imaging and biodistribution studies of 111In-labeled G5-X4 showed enhanced uptake in subcutaneous U87 glioblastoma tumors stably expressing CXCR4 with 8.2 ± 2.1, 8.4 ± 0.5, 11.5 ± 0.9, 10.4 ± 2.6, and 8.8 ± 0.5% injected dose per gram of tissue at 1, 3, 24, 48, and 120 h after injection, respectively. Specific accumulation of [111In]G5-X4 in CXCR4-positive tumors was inhibited by the peptidomimetic CXCR4 inhibitor, POL3026. Our results demonstrate that while CXCR4 targeting is beneficial for tumor accumulation at early time points, differences in tumor uptake are diminished over time as passive accumulation takes place. This study further confirms the applicability of PAMAM dendrimers for imaging and therapeutic applications. It also emphasizes careful consideration of image acquisition and/or treatment times when designing dendritic nanoplatforms for tumor targeting. Full article
(This article belongs to the Special Issue Nanoparticle Delivery to Tumors: Challenges and Advances)
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14 pages, 9635 KiB  
Article
A Dual-Reporter Platform for Screening Tumor-Targeted Extracellular Vesicles
by Masamitsu Kanada, Lauren Linenfelser, Elyssa Cox and Assaf A. Gilad
Pharmaceutics 2022, 14(3), 475; https://doi.org/10.3390/pharmaceutics14030475 - 22 Feb 2022
Cited by 6 | Viewed by 2418
Abstract
Extracellular vesicle (EV)-mediated transfer of biomolecules plays an essential role in intercellular communication and may improve targeted drug delivery. In the past decade, various approaches to EV surface modification for targeting specific cells or tissues have been proposed, including genetic engineering of parental [...] Read more.
Extracellular vesicle (EV)-mediated transfer of biomolecules plays an essential role in intercellular communication and may improve targeted drug delivery. In the past decade, various approaches to EV surface modification for targeting specific cells or tissues have been proposed, including genetic engineering of parental cells or postproduction EV engineering. However, due to technical limitations, targeting moieties of engineered EVs have not been thoroughly characterized. Here, we report the bioluminescence resonance energy transfer (BRET) EV reporter, PalmReNL-based dual-reporter platform for characterizing the cellular uptake of tumor-homing peptide (THP)-engineered EVs, targeting PDL1, uPAR, or EGFR proteins expressed in MDA-MB-231 breast cancer cells, simultaneously by bioluminescence measurement and fluorescence microscopy. Bioluminescence analysis of cellular EV uptake revealed the highest binding efficiency of uPAR-targeted EVs, whereas PDL1-targeted EVs showed slower cellular uptake. EVs engineered with two known EGFR-binding peptides via lipid nanoprobes did not increase cellular uptake, indicating that designs of EGFR-binding peptide conjugation to the EV surface are critical for functional EV engineering. Fluorescence analysis of cellular EV uptake allowed us to track individual PalmReNL-EVs bearing THPs in recipient cells. These results demonstrate that the PalmReNL-based EV assay platform can be a foundation for high-throughput screening of tumor-targeted EVs. Full article
(This article belongs to the Special Issue Nanoparticle Delivery to Tumors: Challenges and Advances)
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17 pages, 3821 KiB  
Article
A Unique Core–Shell Structured, Glycol Chitosan-Based Nanoparticle Achieves Cancer-Selective Gene Delivery with Reduced Off-Target Effects
by Bei Cheng, Hye-Hyun Ahn, Hwanhee Nam, Zirui Jiang, Feng J. Gao, Il Minn and Martin G. Pomper
Pharmaceutics 2022, 14(2), 373; https://doi.org/10.3390/pharmaceutics14020373 - 7 Feb 2022
Cited by 9 | Viewed by 2629
Abstract
The inherent instability of nucleic acids within serum and the tumor microenvironment necessitates a suitable vehicle for non-viral gene delivery to malignant lesions. A specificity-conferring mechanism is also often needed to mitigate off-target toxicity. In the present study, we report a stable and [...] Read more.
The inherent instability of nucleic acids within serum and the tumor microenvironment necessitates a suitable vehicle for non-viral gene delivery to malignant lesions. A specificity-conferring mechanism is also often needed to mitigate off-target toxicity. In the present study, we report a stable and efficient redox-sensitive nanoparticle system with a unique core–shell structure as a DNA carrier for cancer theranostics. Thiolated polyethylenimine (PEI-SH) is complexed with DNA through electrostatic interactions to form the core, and glycol chitosan-modified with succinimidyl 3-(2-pyridyldithio)propionate (GCS-PDP) is grafted on the surface through a thiolate-disulfide interchange reaction to form the shell. The resulting nanoparticles, GCS-PDP/PEI-SH/DNA nanoparticles (GNPs), exhibit high colloid stability in a simulated physiological environment and redox-responsive DNA release. GNPs not only show a high and redox-responsive cellular uptake, high transfection efficiency, and low cytotoxicity in vitro, but also exhibit selective tumor targeting, with minimal toxicity, in vivo, upon systemic administration. Such a performance positions GNPs as viable candidates for molecular-genetic imaging and theranostic applications. Full article
(This article belongs to the Special Issue Nanoparticle Delivery to Tumors: Challenges and Advances)
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9 pages, 2266 KiB  
Article
Two Laser Treatments Can Improve Tumor Ablation Efficiency of Chemophototherapy
by Sanjana Ghosh and Jonathan F. Lovell
Pharmaceutics 2021, 13(12), 2183; https://doi.org/10.3390/pharmaceutics13122183 - 17 Dec 2021
Cited by 3 | Viewed by 2235
Abstract
Chemophototherapy is an emerging tumor ablation modality that can improve local delivery of chemotherapeutic agents. Long circulating doxorubicin (Dox) in porphyrin-phospholipid (PoP) liposomes (LC-Dox-PoP) has previously been developed as an effective chemophototherapy agent. In the present study, we observed that in mice, LC-Dox-PoP [...] Read more.
Chemophototherapy is an emerging tumor ablation modality that can improve local delivery of chemotherapeutic agents. Long circulating doxorubicin (Dox) in porphyrin-phospholipid (PoP) liposomes (LC-Dox-PoP) has previously been developed as an effective chemophototherapy agent. In the present study, we observed that in mice, LC-Dox-PoP showed enhanced accumulation in human pancreatic tumor xenografts even with suboptimal light doses, as assessed by fluorometric analysis of tissue homogenates and microscopic imaging of Dox and PoP in tumor slices. A second laser treatment, at a time point in which tumors had greater drug accumulation as a result of the first laser treatment, induced potent tumor ablation. Efficacy studies were carried out in two human pancreatic cancer subcutaneous mouse tumor models; MIA PaCa-2 or low-passage patient derived pancreatic cancer xenografts. A single treatment of 3 mg/kg LC-Dox-PoP and an initial 150 J/cm2 laser treatment 1 h after drug administration, followed by second laser treatment of 50 J/cm2 8 h after drug administration, was more effective than a single laser treatment of 200 J/cm2 at either of those time points. Thus, this study presents proof-of-principle and rationale for using two discrete laser treatments to enhance the efficacy of chemophototherapy. Full article
(This article belongs to the Special Issue Nanoparticle Delivery to Tumors: Challenges and Advances)
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Review

Jump to: Research

24 pages, 2865 KiB  
Review
Nanocarriers as a Delivery Platform for Anticancer Treatment: Biological Limits and Perspectives in B-Cell Malignancies
by Sara Bozzer, Michele Dal Bo, Maria Cristina Grimaldi, Giuseppe Toffoli and Paolo Macor
Pharmaceutics 2022, 14(9), 1965; https://doi.org/10.3390/pharmaceutics14091965 - 17 Sep 2022
Cited by 6 | Viewed by 1905
Abstract
Nanoparticle-based therapies have been proposed in oncology research using various delivery methods to increase selectivity toward tumor tissues. Enhanced drug delivery through nanoparticle-based therapies could improve anti-tumor efficacy and also prevent drug resistance. However, there are still problems to overcome, such as the [...] Read more.
Nanoparticle-based therapies have been proposed in oncology research using various delivery methods to increase selectivity toward tumor tissues. Enhanced drug delivery through nanoparticle-based therapies could improve anti-tumor efficacy and also prevent drug resistance. However, there are still problems to overcome, such as the main biological interactions of nanocarriers. Among the various nanostructures for drug delivery, drug delivery based on polymeric nanoparticles has numerous advantages for controlling the release of biological factors, such as the ability to add a selective targeting mechanism, controlled release, protection of administered drugs, and prolonging the circulation time in the body. In addition, the functionalization of nanoparticles helps to achieve the best possible outcome. One of the most promising applications for nanoparticle-based drug delivery is in the field of onco-hematology, where there are many already approved targeted therapies, such as immunotherapies with monoclonal antibodies targeting specific tumor-associated antigens; however, several patients have experienced relapsed or refractory disease. This review describes the major nanocarriers proposed as new treatments for hematologic cancer, describing the main biological interactions of these nanocarriers and the related limitations of their use as drug delivery strategies. Full article
(This article belongs to the Special Issue Nanoparticle Delivery to Tumors: Challenges and Advances)
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26 pages, 5235 KiB  
Review
Molecular Imaging of Brain Tumors and Drug Delivery Using CEST MRI: Promises and Challenges
by Jianpan Huang, Zilin Chen, Se-Weon Park, Joseph H. C. Lai and Kannie W. Y. Chan
Pharmaceutics 2022, 14(2), 451; https://doi.org/10.3390/pharmaceutics14020451 - 20 Feb 2022
Cited by 13 | Viewed by 4033
Abstract
Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) detects molecules in their natural forms in a sensitive and non-invasive manner. This makes it a robust approach to assess brain tumors and related molecular alterations using endogenous molecules, such as proteins/peptides, and drugs [...] Read more.
Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) detects molecules in their natural forms in a sensitive and non-invasive manner. This makes it a robust approach to assess brain tumors and related molecular alterations using endogenous molecules, such as proteins/peptides, and drugs approved for clinical use. In this review, we will discuss the promises of CEST MRI in the identification of tumors, tumor grading, detecting molecular alterations related to isocitrate dehydrogenase (IDH) and O-6-methylguanine-DNA methyltransferase (MGMT), assessment of treatment effects, and using multiple contrasts of CEST to develop theranostic approaches for cancer treatments. Promising applications include (i) using the CEST contrast of amide protons of proteins/peptides to detect brain tumors, such as glioblastoma multiforme (GBM) and low-grade gliomas; (ii) using multiple CEST contrasts for tumor stratification, and (iii) evaluation of the efficacy of drug delivery without the need of metallic or radioactive labels. These promising applications have raised enthusiasm, however, the use of CEST MRI is not trivial. CEST contrast depends on the pulse sequences, saturation parameters, methods used to analyze the CEST spectrum (i.e., Z-spectrum), and, importantly, how to interpret changes in CEST contrast and related molecular alterations in the brain. Emerging pulse sequence designs and data analysis approaches, including those assisted with deep learning, have enhanced the capability of CEST MRI in detecting molecules in brain tumors. CEST has become a specific marker for tumor grading and has the potential for prognosis and theranostics in brain tumors. With increasing understanding of the technical aspects and associated molecular alterations detected by CEST MRI, this young field is expected to have wide clinical applications in the near future. Full article
(This article belongs to the Special Issue Nanoparticle Delivery to Tumors: Challenges and Advances)
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36 pages, 1383 KiB  
Review
Salinomycin-Based Drug Delivery Systems: Overcoming the Hurdles in Cancer Therapy
by Lucia Ruxandra Tefas, Cristina Barbălată, Cristian Tefas and Ioan Tomuță
Pharmaceutics 2021, 13(8), 1120; https://doi.org/10.3390/pharmaceutics13081120 - 22 Jul 2021
Cited by 11 | Viewed by 3783
Abstract
Cancer stem cells (CSCs) are reportedly responsible for the initiation and propagation of cancer. Since CSCs are highly resistant to conventional chemo- and radiotherapy, they are considered the main cause of cancer relapse and metastasis. Salinomycin (Sali), an anticoccidial polyether antibiotic, has emerged [...] Read more.
Cancer stem cells (CSCs) are reportedly responsible for the initiation and propagation of cancer. Since CSCs are highly resistant to conventional chemo- and radiotherapy, they are considered the main cause of cancer relapse and metastasis. Salinomycin (Sali), an anticoccidial polyether antibiotic, has emerged as a promising new candidate for cancer therapy, with selective cytotoxicity against CSCs in various malignancies. Nanotechnology provides an efficient means of delivering Sali to tumors in view of reducing collateral damage to healthy tissues and enhancing the therapeutic outcome. This review offers an insight into the most recent advances in cancer therapy using Sali-based nanocarriers. Full article
(This article belongs to the Special Issue Nanoparticle Delivery to Tumors: Challenges and Advances)
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