Supramolecular Host–Guest Chemistry-Based Folate/Riboflavin Functionalization and Cancer Cell Labeling of Nanoparticles

Pal, Suman; Dalal, Chumki; Jana, Nikhil R.

doi:10.1021/acsomega.7b01506

Cited by 12 publications

(8 citation statements)

References 58 publications

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“…The RFVTs were presented at the apical membrane promoting a fast and efficient uptake of riboflavin. This is a highly desired feature of tumor-targeted pharmaceuticals providing an explanation for the promising results obtained with riboflavin-targeted diagnostics (Tsvetkova et al, 2016, 2017; Beztsinna et al, 2017; Pal et al, 2017) and therapeutics (Bareford et al, 2013; Beztsinna et al, 2016) at the in vitro and in vivo level.…”

Section: Discussionmentioning

confidence: 95%

Evaluation of Riboflavin Transporters as Targets for Drug Delivery and Theranostics

et al. 2019

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The retention and cellular internalization of drug delivery systems and theranostics for cancer therapy can be improved by targeting molecules. Since an increased uptake of riboflavin was reported for various cancers, riboflavin and its derivatives may be promising binding moieties to trigger internalization via the riboflavin transporters (RFVT) 1, 2, and 3. Riboflavin is a vitamin with pivotal role in energy metabolism and indispensable for cellular growth. In previous preclinical studies on mice, we showed the target-specific accumulation of riboflavin-functionalized nanocarriers in cancer cells. Although the uptake mechanism of riboflavin has been studied for over a decade, little is known about the riboflavin transporters and their expression on cancer cells, tumor stroma, and healthy tissues. Furthermore, evidence is lacking concerning the representativeness of the preclinical findings to the situation in humans. In this study, we investigated the expression pattern of riboflavin transporters in human squamous cell carcinoma (SCC), melanoma and luminal A breast cancer samples, as well as in healthy skin, breast, aorta, and kidney tissues. Low constitutive expression levels of RFVT1–3 were found on all healthy tissues, while RFVT2 and 3 were significantly overexpressed in melanoma, RFVT1 and 3 in luminal A breast cancer and RFVT1–3 in SCC. Correspondingly, the SCC cell line A431 was highly positive for all RFVTs, thus qualifying as suitable in vitro model. In contrast, activated endothelial cells (HUVEC) only presented with a strong expression of RFVT2, and HK2 kidney cells only with a low constitutive expression of RFVT1–3. Functional in vitro studies on A431 and HK2 cells using confocal microscopy showed that riboflavin uptake is mostly ATP dependent and primarily driven by endocytosis. Furthermore, riboflavin is partially trafficked to the mitochondria. Riboflavin uptake and trafficking was significantly higher in A431 than in healthy kidney cells. Thus, this manuscript supports the hypothesis that addressing the riboflavin internalization pathway may be highly valuable for tumor targeted drug delivery.

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Section: Discussionmentioning

confidence: 95%

Evaluation of Riboflavin Transporters as Targets for Drug Delivery and Theranostics

et al. 2019

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“… 90 , 91 Bio conjugated QDs are also considered for the site-specific gene as well as drug delivery in cancer. Targeting moieties, such as antibodies, 92 high-molecular-weight dextran, 93 aptamers, 94 peptides, 95 or folate, 96 can then be combined with QDs.…”

Section: Various Types Of Nanocarrier-based Drug Delivery Systemsmentioning

confidence: 99%

Nanocarriers-Mediated Drug Delivery Systems for Anticancer Agents: An Overview and Perspectives

Edis¹,

Wang²,

Waqas³

et al. 2021

IJN

220

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Nanotechnology has been actively integrated as drug carriers over the last few years to treat various cancers. The main hurdle in the clinical management of cancer is the development of multidrug resistance against chemotherapeutic agents. To overcome the limitations of chemotherapy, the researchers have been developing technological advances for significant progress in the oncotherapy by enabling the delivery of chemotherapeutic agents at increased drug content levels to the targeted spots. Several nano-drug delivery systems designed for tumor-targeting are evaluated in preclinical and clinical trials and showed promising outcomes in cancerous tumors’ clinical management. This review describes nanocarrier’s importance in managing different types of cancers and emphasizing nanocarriers for drug delivery and cancer nanotherapeutics. It also highlights the recent advances in nanocarriers-based delivery systems, including polymeric nanocarriers, micelles, nanotubes, dendrimers, magnetic nanoparticles, solid lipid nanoparticles, and quantum dots (QDs). The nanocarrier-based composites are discussed in terms of their structure, characteristics, and therapeutic applications in oncology. To conclude, the challenges and future exploration opportunities of nanocarriers in chemotherapeutics are also presented.

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“…Size and morphology influence, e.g., the functionalization capacity of nanoparticles, determine their motional behavior in solution, decide upon their optical properties [63] or the uptake into cells, [64] to name a few. The accessible outer and inner surface-area are the key for specific surface functionalization in host-guest interactions (Section 5) [65] or loading of molecules to nanoparticle drug delivery systems (Section 8.2). [66] In particular in aqueous solution, the surface charge of nanoparticles dominates the interactions between the particle and its surrounding and determine its trend toward aggregation.…”

Section: Characterization Of Reticular Nanoparticlesmentioning

confidence: 99%

The Chemistry of Reticular Framework Nanoparticles: MOF, ZIF, and COF Materials

Ploetz

Engelke

Lächelt

et al. 2020

Adv Funct Materials

231

145

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Nanoparticles have become a vital part of a vast number of established processes and products; they are used as catalysts, in cosmetics, and even by the pharmaceutical industry. Despite this, however, the reliable and reproducible production of functional nanoparticles for specific applications remains a great challenge. In this respect, reticular chemistry provides methods for connecting molecular building blocks to nanoparticles whose chemical composition, structure, porosity, and functionality can be controlled and tuned with atomic precision. Thus, reticular chemistry allows for the translation of the green chemistry principle of atom economy to functional nanomaterials, giving rise to the multifunctional efficiency concept. This principle encourages the design of highly active nanomaterials by maximizing the number of integrated functional units while minimizing the number of inactive components. State-ofthe-art research on reticular nanoparticles-metal-organic frameworks, zeolitic imidazolate frameworks, and covalent organic frameworks-is critically assessed and the beneficial features and particular challenges that set reticular chemistry apart from other nanoparticle material classes are highlighted. Reviewing the power of reticular chemistry, it is suggested that the unique possibility to efficiently and straightforwardly synthesize multifunctional nanoparticles should guide the synthesis of customized nanoparticles in the future.

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Supramolecular Host–Guest Chemistry-Based Folate/Riboflavin Functionalization and Cancer Cell Labeling of Nanoparticles

Cited by 12 publications

References 58 publications

Evaluation of Riboflavin Transporters as Targets for Drug Delivery and Theranostics

Evaluation of Riboflavin Transporters as Targets for Drug Delivery and Theranostics

Nanocarriers-Mediated Drug Delivery Systems for Anticancer Agents: An Overview and Perspectives

The Chemistry of Reticular Framework Nanoparticles: MOF, ZIF, and COF Materials

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