One-component nanomedicine

Su, Hao; Koo, Jin Mo; Cui, Honggang

doi:10.1016/j.jconrel.2015.09.056

Cited by 134 publications

(86 citation statements)

References 192 publications

(159 reference statements)

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“…When gradually diluted in a short-term stability experiment, the self-assembled filament showed a dissociation tendency, which was decreasing with higher drug content. 20 When exposed to mild sonication, dissociation was observed in the case of a similar DA called qCPT-Sub 35 which has four CPT drugs conjugated to a Sub 35 peptide. 90–92 After relaxing the computational system for 200 ns at 300 K, the filament is 0.576 μm.…”

Section: Resultsmentioning

confidence: 99%

“…Peptide-based drug amphiphiles (DAs) as designed by the Cui laboratory 20 are new candidates for drug delivery vehicles with the potential to address many of these issues. 33–35 DAs possess one hundred percent loading capacity, as well as the ability to optimize the delivery of the drug via a biodegradable linker. 36 This biodegradation is one of the key factors in the stability of the drug delivery vehicle, and resulting dissociation and delivery.…”

Section: Introductionmentioning

confidence: 99%

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Coarse-grained molecular dynamics studies of the structure and stability of peptide-based drug amphiphile filaments

2017

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Peptide-based supramolecular filaments, in particular filaments self-assembled by drug amphiphiles (DAs), possess great potential in the field of drug delivery. These filaments possess one hundred percent drug loading, with a release mechanism that can be tuned based on the dissociation of the supramolecular filaments and the degradation of the DAs [Cheetham et al., J. Am. Chem. Soc. 135 (8), 2907 (2013)]. Recently, much attention has been drawn to the competing intermolecular interactions that drive the self-assembly of peptide-based amphiphiles into supramolecular filaments. Recently, we reported on long-time atomistic molecular dynamics simulations to characterize the structure and growth of chiral filaments by the self-assembly of a DA containing the aromatic anti-cancer drug camptothecin [Kang et al., Macromolecules 49 (3), 994 (2016)]. We found that the π–π stacking of the aromatic drug governs the early stages of the self-assembly process, while also contributing towards the chirality of the self-assembled filament. Based on these all-atomistic simulations, we now build a chemically accurate coarse-grained model that can capture the structure and stability of these supramolecular filaments at long time-scales (microseconds). These coarse-grained models successfully recapitulate the growth of the molecular clusters (and their elongation trends) compared with previously reported atomistic simulations. Furthermore, the interfacial structure and the helicity of the filaments are conserved. Next, we focus on characterization of the disassembly process of a 0.675 μm DA filament at microsecond time-scales. These results provide very useful tools for the rational design of functional supramolecular filaments, in particular supramolecular filaments for drug delivery applications.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Coarse-grained molecular dynamics studies of the structure and stability of peptide-based drug amphiphile filaments

2017

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“…[169] Recently, a bifunctional dual-acting prodrug was prepared by conjugating PTX and DOX in the same carrier to realize combinational chemotherapy. The prodrug incorporated a 1,6-self-immolative para-aminobenzyloxycarbonyl (PABC) spacer between the conjugated drug and the lysosomally cleavable dipeptide Phe-Lys.…”

Section: Prodrug Strategiesmentioning

confidence: 99%

Preclinical development of drug delivery systems for paclitaxel-based cancer chemotherapy

Wang

Porter

Konstantopoulos

et al. 2017

Journal of Controlled Release

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Paclitaxel (PTX) is one of the most successful drugs ever used in cancer chemotherapy, acting against a variety of cancer types. Formulating PTX with Cremophor EL and ethanol (Taxol®) realized its clinical potential, but the formulation falls short of expectations due to side effects such as peripheral neuropathy, hypotension, and hypersensitivity. Abraxane®, the albumin bound PTX, represents a superior replacement of Taxol® that mitigates the side effects associated with Cremophor EL. While Abraxane® is now considered a gold standard in chemotherapy, its 21% response rate leaves much room for further improvement. The quest for safer and more effective cancer treatments has led to the development of a plethora of innovative PTX formulations, many of which are currently undergoing clinical trials. In this context, we review recent development of PTX drug delivery systems and analyze the design principles underpinning each delivery strategy. We chose several representative examples to highlight the opportunities and challenges of polymeric systems, lipid-based formulations, as well as prodrug strategies.

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“…This approach aims to take advantage of the potential interactions that the drug has to offer, thus making the drug a vital structural element rather than just a functional unit. The following sections will focus on a number of recent strategies that are being used to further improve the delivery of drugs via construction of nanostructures, creating entities that have been termed one-component nanomedicines [48]. …”

Section: Nanostructure Formed By Free Drugsmentioning

confidence: 99%

Building nanostructures with drugs

2016

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The convergence of nanoscience and drug delivery has prompted the formation of the field of nanomedicine, one that exploits the novel physicochemical and biological properties of nanostructures for improved medical treatments and reduced side effects. Until recently, this nanostructure-mediated strategy considered the drug to be solely a biologically active compound to be delivered, and its potential as a molecular building unit remained largely unexplored. A growing trend within nanomedicine has been the use of drug molecules to build well-defined nanostructures of various sizes and shapes. This strategy allows for the creation of self-delivering supramolecular nanomedicines containing a high and fixed drug content. Through rational design of the number and type of the drug incorporated, the resulting nanostructures can be tailored to assume various morphologies (e.g. nanospheres, rods, nanofibers, or nanotubes) for a particular mode of administration such as systemic, topical, and local delivery. This review covers the recent advances in this rapidly developing field, with the aim of providing an in-depth evaluation of the exciting opportunities that this new field could create to improve the current clinical practice of nanomedicine.

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One-component nanomedicine

Cited by 134 publications

References 192 publications

Coarse-grained molecular dynamics studies of the structure and stability of peptide-based drug amphiphile filaments

Coarse-grained molecular dynamics studies of the structure and stability of peptide-based drug amphiphile filaments

Preclinical development of drug delivery systems for paclitaxel-based cancer chemotherapy

Building nanostructures with drugs

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