A Supramolecular Approach for Preparation of Size‐Controlled Nanoparticles

Wang, Hao; Wang, Shutao; Su, Helen C.; Chen, Kuan‐Ju; Armijo, Amanda L.; Lin, Wei‐Yu; Wang, Yanju; Sun, Jing; Kamei, Kazuhito; Czernin, Johannes; Radu, Caius G.; Tseng, Hsian-Rong

doi:10.1002/ange.200900063

Cited by 58 publications

(88 citation statements)

References 34 publications

(27 reference statements)

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“…Although most clinically approved anticancer NMs have size ranging from 100 to 200 nm (8,9), recent studies showed that anticancer NMs with smaller sizes exhibited enhanced performance in vivo, such as greater tissue penetration and enhanced tumor inhibition, particularly those with size around or smaller than 50 nm (5)(6)(7)(10)(11)(12). As such, there has been a major push recently in the field of anticancer NM to miniaturize nanoparticle (NP) size using novel chemistry and engineering design (13)(14)(15)(16)(17).…”

mentioning

confidence: 99%

Investigating the optimal size of anticancer nanomedicine

Tang

Yang²,

Yin

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

561

378

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Nanomedicines (NMs) offer new solutions for cancer diagnosis and therapy. However, extension of progression-free interval and overall survival time achieved by Food and Drug Administrationapproved NMs remain modest. To develop next generation NMs to achieve superior anticancer activities, it is crucial to investigate and understand the correlation between the physicochemical properties of NMs (particle size in particular) and their interactions with biological systems to establish criteria for NM optimization. Here, we systematically evaluated the size-dependent biological profiles of three monodisperse drug-silica nanoconjugates (NCs; 20, 50, and 200 nm) through both experiments and mathematical modeling and aimed to identify the optimal size for the most effective anticancer drug delivery. Among the three NCs investigated, the 50-nm NC shows the highest tumor tissue retention integrated over time, which is the collective outcome of deep tumor tissue penetration and efficient cancer cell internalization as well as slow tumor clearance, and thus, the highest efficacy against both primary and metastatic tumors in vivo.O ver the last two to three decades, consensus has been reached that the size of anticancer nanomedicines (NMs) plays a pivotal role in determining their biodistribution, tumor penetration, cellular internalization, and clearance from blood plasma and tissues as well as excretion from body, and thus, it has significant impact on overall therapeutic efficacy against cancers (1-7). Although most clinically approved anticancer NMs have size ranging from 100 to 200 nm (8, 9), recent studies showed that anticancer NMs with smaller sizes exhibited enhanced performance in vivo, such as greater tissue penetration and enhanced tumor inhibition, particularly those with size around or smaller than 50 nm (5-7, 10-12). As such, there has been a major push recently in the field of anticancer NM to miniaturize nanoparticle (NP) size using novel chemistry and engineering design (13-17). One unanswered question, however, is whether additional miniaturization of NM size would be necessary and result in additional improved anticancer efficacy. Widely evaluated small molecular therapeutics (<1,500 Da and <2 nm) can traverse most tumor tissues freely (18). However, they diffuse away from tumor tissues rapidly and get cleared primarily into tumor blood capillaries, leading to minimal tumor accumulation (18). Macromolecules of relatively low molecular masses (<40,000 Da and <10 nm) were also shown to have low overall tumor retention because of both rapid permeation into and clearance from tumor tissues, behaving to some extent like small molecule drugs (18,19). In conjunction with the renal clearance threshold (<10-15 nm) (20, 21) and interstitial/lymphatic fenestration (<20 nm) (22) for NPs, it becomes essential to carefully and comprehensively evaluate the in vivo behavior and anticancer efficacy of NMs in the size range of 20-50 nm to determine the optimal size of NM for cancer therapy.In this study, we used monodisper...

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mentioning

confidence: 99%

Investigating the optimal size of anticancer nanomedicine

Tang

Yang²,

Yin

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

561

378

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“…Recent reports have highlighted the need for systematic investigation of unknown, but potentially harmful, effects of nanomaterials in order to permit safer design and application in biomedicine. [1][2][3][4] Ultrafine ambient particles (diameter ,100 nm) overlap in size with engineered nanomaterials. Systematic studies of toxicity/trafficking of defined/ trackable engineered nanomaterials in the lung as a portal of entry to the systemic circulation and end organs would provide insight into the environmental health effects of air pollution and design of inhaled drug delivery systems.…”

Section: Introductionmentioning

confidence: 99%

Translocation of PEGylated quantum dots across rat alveolar epithelial cell monolayers

Fazlollahi¹,

Sipos²,

Kim³

et al. 2011

IJN

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Background: In this study, primary rat alveolar epithelial cell monolayers (RAECM) were used to investigate transalveolar epithelial quantum dot trafficking rates and underlying transport mechanisms. Methods: Trafficking rates of quantum dots (PEGylated CdSe/ZnS, core size 5.3 nm, hydrodynamic size 25 nm) in the apical-to-basolateral direction across RAECM were determined. Changes in bioelectric properties (ie, transmonolayer resistance and equivalent active ion transport rate) of RAECM in the presence or absence of quantum dots were measured. Involvement of endocytic pathways in quantum dot trafficking across RAECM was assessed using specific inhibitors (eg, methyl-β-cyclodextrin, chlorpromazine, and dynasore for caveolin-, clathrin-, and dynamin-mediated endocytosis, respectively). The effects of lowering tight junctional resistance on quantum dot trafficking were determined by depleting Ca 2+ in apical and basolateral bathing fluids of RAECM using 2 mM EGTA. Effects of temperature on quantum dot trafficking were studied by lowering temperature from 37°C to 4°C. Results: Apical exposure of RAECM to quantum dots did not elicit changes in transmonolayer resistance or ion transport rate for up to 24 hours; quantum dot trafficking rates were not surface charge-dependent; methyl-β-cyclodextrin, chlorpromazine, and dynasore did not decrease quantum dot trafficking rates; lowering of temperature decreased transmonolayer resistance by approximately 90% with a concomitant increase in quantum dot trafficking by about 80%; and 24 hours of treatment of RAECM with EGTA decreased transmonolayer resistance by about 95%, with increased quantum dot trafficking of up to approximately 130%. Conclusion: These data indicate that quantum dots do not injure RAECM and that quantum dot trafficking does not appear to take place via endocytic pathways involving caveolin, clathrin, or dynamin. We conclude that quantum dot translocation across RAECM takes place via both transcellular and paracellular pathways and, based on comparison with our prior studies, interactions of nanoparticles with RAECM are strongly dependent on nanoparticle composition and surface properties.

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“…Moreover, the structures and syntheses of the entire of this family are important for their binding of a broad range of guests, utilizing a collection of interactions. [2][3][4][5][6][7][8][9][10] Bacteria digest starch comprise of an unrefined blend of linear, cyclodextrins plus proteins, and other impurities. Isolation of pure CDs is a difficult task.…”

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confidence: 99%

Computer‐aided drug design to explore cyclodextrin therapeutics and biomedical applications

Abdolmaleki

Ghasemi

2017

Chem Biol Drug Des

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Cyclodextrin (CD) is a subset of the macrocyclic structural class, which is an important class of small organic agents that are useful functional excipients. They have wide range application possibilities in different fields of sciences such as material preparation, medicine, analytical chemistry, and separation processes. They are used widely in pharmaceutical formulations and drug delivery for increasing the water solubility of low soluble drugs and drug candidates. Due to the ring structure, they behave differently than smaller molecules and may be capable of hitting new classes of targets. A macrocyclic molecule presents varied functionality and stereochemical complexity in a pre-organized conformation of the ring structure. This can result in high selectivity and affinity for protein targets while conserving enough bioavailability to arrive at intracellular locations. Regardless of these valuable features, and the verified success of several marketed macrocycle drugs isolated from natural compounds, this class has been little explored in drug development. This study describes some of the key features of the CDs therapeutic discovery. Also, the application of computational chemistry approaches such as QSAR/QSPR, molecular docking, and molecular/quantum mechanics for modeling of CD-drug system is reviewed briefly. K E Y W O R D Sbioavailability, computational, cyclodextrin, drug design, drug discovery, macrocyclic, therapeutic

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A Supramolecular Approach for Preparation of Size‐Controlled Nanoparticles

Cited by 58 publications

References 34 publications

Investigating the optimal size of anticancer nanomedicine

Investigating the optimal size of anticancer nanomedicine

Translocation of PEGylated quantum dots across rat alveolar epithelial cell monolayers

Computer‐aided drug design to explore cyclodextrin therapeutics and biomedical applications

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