Bilirubin Nanoparticles as a Nanomedicine for Anti‐inflammation Therapy

Lee, Yonghyun; Kim, Hyungjun; Kang, Sukmo; Lee, Jinju; Park, Jinho; Jon, Sangyong

doi:10.1002/anie.201602525

Cited by 166 publications

(109 citation statements)

References 34 publications

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“…However, most hydrophobic chemotherapeutics alone cannot self-assemble into stable nanoprecipitates in aqueous media without the help of adjuvant matrices. By exploiting the innate hydrophobicity of therapeutics, various amphiphilic prodrugs covalently coupled with hydrophilic motifs [e.g., oligo(ethylene glycol) (17)(18)(19), polypeptides (20,21), and copolymers (22)(23)(24)(25)] have been leveraged to mimic the self-assembly behavior that ubiquitously occurs in nature. More intriguingly, several groups, including us, have recently demonstrated that the attachment of lipophilic moieties to anticancer agents conferred the prodrug amphiphiles with the ability to form colloidally stable nanoaggregates rather than precipitants, despite the enhanced overall lipophilicity of prodrugs (26)(27)(28)(29)(30)(31).…”

Section: Introductionmentioning

confidence: 99%

New Generation Nanomedicines Constructed from Self-Assembling Small-Molecule Prodrugs Alleviate Cancer Drug Toxicity

et al. 2017

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The therapeutic index for chemotherapeutic drugs is determined in part by systemic toxicity, so strategies for dose intensification to improve efficacy must also address tolerability. In addressing this issue, we have investigated a novel combinatorial strategy of reconstructing a drug molecule and using sequential drug-induced nanoassembly to fabricate supramolecular nanomedicines (SNM). Using cabazitaxel as a target agent, we established that individual synthetic prodrugs tethered with polyunsaturated fatty acids were capable of recapitulating self-assembly behavior independent of exogenous excipients. The resulting SNM could be further refined by PEGylation with amphiphilic copolymers suitable for preclinical studies. Among these cabazitaxel derivatives, docosahexaenoic acid-derived compound 1 retained high antiproliferative activity. SNM assembled with compound 1 displayed an unexpected enhancement of tolerability in animals along with effective therapeutic efficacy in a mouse xenograft model of human cancer, compared with free drug administered in its clinical formulation. Overall, our studies showed how attaching flexible lipid chains to a hydrophobic and highly toxic anticancer drug can convert it to a systemic self-deliverable nanotherapy, preserving its pharmacologic efficacy while improving its safety profile. Cancer Res; 77(24); 6963-74. Ó2017 AACR.

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Section: Introductionmentioning

confidence: 99%

New Generation Nanomedicines Constructed from Self-Assembling Small-Molecule Prodrugs Alleviate Cancer Drug Toxicity

et al. 2017

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“…What happens during the phototherapy caught our attention. [13] However,the multistimuli-responsiveness of BRNPs and its potential as asmart drug-delivery carrier have not been investigated in the report. Interestingly,u pon irradiation with ap roper wavelength of light, bilirubin undergoes photoisomerization (via the breaking of intramolecular hydrogen bonds) and is converted into several photoisomers,a ll of which have much higher water solubility and thus are easily processed and excreted by the liver and kidneys.…”

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confidence: 99%

Multistimuli‐Responsive Bilirubin Nanoparticles for Anticancer Therapy

Lee

et al. 2016

Angew Chem Int Ed

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Although stimuli-responsive materials hold potential for use as drug-delivery carriers for treating cancers,t heir clinical translation has been limited. Ideally,materials used for the purpose should be biocompatible and nontoxic,p rovide "on-demand" drug release in response to internal or external stimuli, allowl arge-scale manufacturing,a nd exhibit intrinsic anticancer efficacy.W ep resent multistimuli-responsive nanoparticles formed from bilirubin, ap otent endogenous antioxidant that possesses intrinsic anticancer and anti-inflammatory activity.E xposure of the bilirubin nanoparticles (BRNPs) to either reactive oxygen species (ROS)o re xternal laser light causes rapid disruption of the BRNP nanostructure as aresult of as witch in bilirubin solubility,t hereby releasing encapsulated drugs.I naxenograft tumor model, BRNPs loaded with the anticancer drug doxorubicin (DOX@BRNPs), when combined with laser irradiation of 650 nm, significantly inhibited tumor growth. This study suggests that BRNPs may be used as ad rug-delivery carrier as well as ac ompanion medicine for effectively treating cancers.

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“…These BRNPs had a potent therapeutic effect in an animal model of acute inflammatory diseases. [55] Ischemia-reperfusion injury (IRI) is a major problem that may occur after liver transplantation. These PEG-BR molecules then self-assembled into nanoscale BRNPs, with a diameter of about 110 nm.…”

Section: Bilirubinmentioning

confidence: 99%

“…Reproduced with permission [55]. BRNPs self-assemble into nanoparticles after PEGylation of bilirubin.…”

mentioning

confidence: 99%

Naturally Occurring Bioactive Compound‐Derived Nanoparticles for Biomedical Applications

Saw

Lee

Jon

2019

Advanced Therapeutics

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Bioactive, small molecular compounds from a variety of plants and organisms have tremendous potential for use as treatments for cancer, microbial infections, inflammatory diseases, and other medical conditions. There have also been attempts to use naturally occurring bioactive compounds as delivery carriers. Such bioactive, natural compound-derived nanocarriers are expected to have better biocompatibility than synthetic material-derived drug-delivery systems and also exhibit intrinsic therapeutic efficacy. Despite these expectations, however, research on the topic is limited and thus has been the subject of very few reviews. Here, the authors describe carriers derived from four typical naturally occurring bioactive compounds-curcumin, resveratrol, epigallocatechin gallate (EGCG) (an active ingredient in green tea), and bilirubin-that have been used for biomedical applications. In this review, the pros and cons of each bioactive small molecular compound and processes for synthesizing and preparing these compound-derived delivery carriers are discussed. A number of examples that show the potential of these delivery carriers as disease treatments are considered, and their future prospects for biomedical applications are assessed. Nanoparticles that simply encapsulate or encase such bioactive compounds are outside the scope of this review and thus are not considered.

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Bilirubin Nanoparticles as a Nanomedicine for Anti‐inflammation Therapy

Cited by 166 publications

References 34 publications

New Generation Nanomedicines Constructed from Self-Assembling Small-Molecule Prodrugs Alleviate Cancer Drug Toxicity

New Generation Nanomedicines Constructed from Self-Assembling Small-Molecule Prodrugs Alleviate Cancer Drug Toxicity

Multistimuli‐Responsive Bilirubin Nanoparticles for Anticancer Therapy

Naturally Occurring Bioactive Compound‐Derived Nanoparticles for Biomedical Applications

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