Nanoparticle-Based Passive Drug Targeting to Tumors: Considerations and Implications for Optimization

Ogawara, Ken Ichi; Yoshizawa, Yuta; Un, Keita; Araki, Tomoya; Kimura, Toshikiro; Higaki, Kazutaka

doi:10.1248/bpb.b13-00015

Cited by 18 publications

(11 citation statements)

References 22 publications

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“…Overall, TDP-A-loaded targeted micelles were the most effective in retarding tumor growth among the various groups studied including TDP-A-loaded non-targeted micelles and free TDP-A. This observation can be largely contributed to the fact that the TDP-A-loaded, OCT-conjugated NET-targeting unimolecular micelles have both passive (via the EPR effect [45,46]) and active (via OCT conjugation) tumor targeting abilities [47–49]. In contrast, the TDP-A-loaded non-targeted unimolecular micelles only have passive tumor targeting ability, while free TDP-A does not have any specific tumor targeting ability resulting in high in vivo systemic toxicity.…”

Section: Resultsmentioning

confidence: 99%

Thailandepsin A-loaded and octreotide-functionalized unimolecular micelles for targeted neuroendocrine cancer therapy

Jaskula-Sztul

Chen

et al. 2016

Biomaterials

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Due to the overexpression of somatostatin receptors in neuroendocrine (NE) cancers, drug nanocarriers conjugated with somatostatin analogs, such as octreotide (OCT), for targeted NE cancer therapy may offer increased therapeutic efficacies and decreased adverse effects. In this study, OCT-functionalized unimolecular micelles were prepared using individual hyperbranched polymer molecules consisting of a hyperbranched polymer core (Boltorn® H40) and approximately 25 amphiphilic polylactide-poly(-ethlyene glycol) (PLA-PEG) block copolymer arms (H40-PLA-PEG-OCH3/OCT). The resulting micelles, exhibiting a uniform core-shell shape and an average hydrodynamic diameter size of 66 nm, were loaded with thailandepsin-A (TDP-A), a relatively new naturally produced histone deacetylase (HDAC) inhibitor. In vitro studies using flow cytometry and confocal laser scanning microscopy (CLSM) demonstrated that OCT conjugation enhanced the cellular uptake of the unimolecular micelles. Consequently, TDP-A-loaded and OCT-conjugated micelles exhibited the highest cytotoxicity and caused the highest reduction of NE tumor markers. Finally, the in vivo studies on NE cancer bearing nude mice demonstrated that TDP-A-loaded and OCT-conjugated micelles possessed superior anticancer activity in comparison with other TDP-A formulations or drug alone, while showing no detectable systemic toxicity. Thus, these TDP-A-loaded and OCT-conjugated micelles offer a promising approach for targeted NE cancer therapy.

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Section: Resultsmentioning

confidence: 99%

Thailandepsin A-loaded and octreotide-functionalized unimolecular micelles for targeted neuroendocrine cancer therapy

Jaskula-Sztul

Chen

et al. 2016

Biomaterials

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“…In addition, using this strategy, passive accumulation of the DDS in the tumor environment can be achieved, which is called the enhanced permeability and retention effect. 22 , 23 Furthermore, targeted delivery of the drug can be achieved by several receptors overexpressed on some tumor cells, such as asialoglycoproteins, 24 transferrin, 25 integrin receptors 26 , 27 and folate. 28 …”

Section: Potential Strategies To Enhance Chemotherapy By 5-fumentioning

confidence: 99%

<p>Recent Advances in Designing 5-Fluorouracil Delivery Systems: A Stepping Stone in the Safe Treatment of Colorectal Cancer</p>

Entezar-Almahdi¹,

Mohammadi-Samani²,

Tayebi³

et al. 2020

IJN

124

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5-Fluorouracil (5-FU) has become one of the most widely employed antimetabolite chemotherapeutic agents in recent decades. It is considered a first line antineoplastic agent for the treatment of colorectal cancer. Unfortunately, chemotherapy with 5-FU has several limitations, including its short half-life, high cytotoxicity and low bioavailability. In order to overcome the drawbacks of 5-FU and enhance its therapeutic efficiency, many scientific groups have focused on designing a new delivery system to successfully deliver 5-FU to tumor sites. We provide a comprehensive review on different strategies to design effective delivery systems, including nanoformulations, drug-conjugate formulations and other strategies for the delivery of 5-FU to colorectal cancer. Furthermore, co-delivery of 5-FU with other therapeutics is discussed. This review critically highlights the recent innovations in and literature on various types of carrier system for 5-FU.

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“…Targeting is achieved through either active or passive means. Active targeting (Nag and Delehanty, 2019) involves a specific ligand functionalized to the nanoparticle exterior that binds to receptors that are overexpressed in the outer cell membrane of cells of the target tissue and passive targeting involves global properties (Ogawara et al, 2013) of the nanoparticle that lead to a greater percentage becoming lodged in the target tissue in comparison to other tissues. An example of passive targeting is what is referred to as the enhanced permeability and retention (EPR) effect (Maeda et al, 2013); liposomes can be designed to take advantage of the leaky vasculature of tumor tissue to become preferentially lodged there; PEGylation is a common means to achieve this.…”

Section: Nanoparticle Design and Functionmentioning

confidence: 99%

Mechanistic Understanding From Molecular Dynamics Simulation in Pharmaceutical Research 1: Drug Delivery

Bunker

Róg

2020

Front. Mol. Biosci.

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In this review, we outline the growing role that molecular dynamics simulation is able to play as a design tool in drug delivery. We cover both the pharmaceutical and computational backgrounds, in a pedagogical fashion, as this review is designed to be equally accessible to pharmaceutical researchers interested in what this new computational tool is capable of and experts in molecular modeling who wish to pursue pharmaceutical applications as a context for their research. The field has become too broad for us to concisely describe all work that has been carried out; many comprehensive reviews on subtopics of this area are cited. We discuss the insight molecular dynamics modeling has provided in dissolution and solubility, however, the majority of the discussion is focused on nanomedicine: the development of nanoscale drug delivery vehicles. Here we focus on three areas where molecular dynamics modeling has had a particularly strong impact: (1) behavior in the bloodstream and protective polymer corona, (2) Drug loading and controlled release, and (3) Nanoparticle interaction with both model and biological membranes. We conclude with some thoughts on the role that molecular dynamics simulation can grow to play in the development of new drug delivery systems.

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Nanoparticle-Based Passive Drug Targeting to Tumors: Considerations and Implications for Optimization

Cited by 18 publications

References 22 publications

Thailandepsin A-loaded and octreotide-functionalized unimolecular micelles for targeted neuroendocrine cancer therapy

Thailandepsin A-loaded and octreotide-functionalized unimolecular micelles for targeted neuroendocrine cancer therapy

<p>Recent Advances in Designing 5-Fluorouracil Delivery Systems: A Stepping Stone in the Safe Treatment of Colorectal Cancer</p>

Mechanistic Understanding From Molecular Dynamics Simulation in Pharmaceutical Research 1: Drug Delivery

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