Tunable Lipidoid‐Telodendrimer Hybrid Nanoparticles for Intracellular Protein Delivery in Brain Tumor Treatment

Wang, Xu; Bodman, Alexa; Shi, Changying; Guo, Dandan; Wang, Lili; Luo, Juntao; Hall, Walter A.

doi:10.1002/smll.201601234

Cited by 17 publications

(13 citation statements)

References 51 publications

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“…[62, 63] DOX has a positively charged amine group, which should be able to migrate under electric field. Being stably loaded in a nanocarrier, DOX should be trapped in the loading well due to the size effects.…”

Section: Resultsmentioning

confidence: 99%

Riboflavin-containing telodendrimer nanocarriers for efficient doxorubicin delivery: High loading capacity, increased stability, and improved anticancer efficacy

et al. 2017

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We have developed two linear-dendritic telodendrimers (TDs) with rational design using amphiphilic riboflavin (Rf) as building blocks for efficient doxorubicin (DOX) delivery. Micellar TD nanoparticles (NPs) are composed of a hydrophilic polyethylene glycol (PEG) shell and a Rf-containing affinitive core for DOX encapsulation. Strong DOX-Rf interactions and amphiphilic Rf structure render these nanocarriers with an ultra-high DOX loading capacity (>1/1, DOX/TD, w/w), ~100% loading efficiency, the sustained drug release and the optimal particle sizes (20~40 nm) for efficient tumor-targeted drug delivery. These nanoformulations significantly prolonged DOX circulation time in the blood without the accelerated clearance observed after multiple injections. DOX-TDs target several types of tumors efficiently in vivo, e.g. Raji lymphoma, MDA-MB-231 breast cancer, and SKOV3 ovarian cancer. In vivo maximum tolerated dose (MTD) of DOX was increased by 2~2.5 folds for the nanoformulations in mice relative to those of free DOX and Doxil®. These nanoformulations significantly inhibited tumor growth and prolonged survival of mice bearing SKOV3 ovarian cancer xenografts. In summary, Rf-containing nanoformulations with high DOX loading capacity, improved stability and efficient tumor targeting lead to superior antitumor efficacy, which merit the further development for clinical application.

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Section: Resultsmentioning

confidence: 99%

Riboflavin-containing telodendrimer nanocarriers for efficient doxorubicin delivery: High loading capacity, increased stability, and improved anticancer efficacy

et al. 2017

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“…The polycationic molecules or complexes were reported to be toxic for many cell lines. [2, 4, 34] HT-29 colon cancer cell line was selected as a model cell line to investigate the cytotoxicity of protein-polycation and protein-polycation-PEG 5k (OAOA-L-CHO) 4 nanocomplexes. The cell viability results after a 72-h continuous incubation at 37 °C in Fig.…”

Section: Resultsmentioning

confidence: 99%

Polycation-telodendrimer nanocomplexes for intracellular protein delivery

Wang

Shi

Wang

et al. 2018

Colloids and Surfaces B: Biointerfaces

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Intracellular delivery of protein therapeutics by cationic polymer vehicles is an emerging technique that is, however, encountering poor stability, high cytotoxicity and non-specific cell uptake. Herein, we present a facile strategy to optimize the protein-polycation complexes by encapsulating with linear-dendritic telodendrimers. The telodendrimers with well-defined structures enable the rational design and integration of multiple functionalities for efficient encapsulation of the protein-polycation complexes by multivalent and hybrid supramolecular interactions to produce sub-20 nm nanoparticles. This strategy not only reduces the polycation-associated cytotoxicity and hemolytic activity, but also eliminates the aggregation and non-specific binding of polycations to other biomacromolecules. Moreover, the telodendrimers dissociate readily from the complexes during the cellular uptake process, which restores the capability of polycations for intracellular protein delivery. This strategy overcomes the limitations of polycationic vectors for intracellular delivery of protein therapeutics.

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“…In another interesting study, telodendrimers based on PEG-poly(lysine) containing cholic acid and/or cholesterol were investigated for the delivery of proteins across the blood–brain barrier. Using bovine serum albumin functionalized with fluorescent dye Cy5, it was found that telodendrimers assisted and improved the delivery of the protein into the brain [ 207 ]. The results are interesting, and suggest that the telodendrimer can overcome significant challenges in drug delivery across the blood–brain barrier.…”

Section: Telodendrimersmentioning

confidence: 99%

Telodendrimers: Promising Architectural Polymers for Drug Delivery

Mejlsøe

Kakkar

2020

Molecules

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Architectural complexity has played a key role in enhancing the efficacy of nanocarriers for a variety of applications, including those in the biomedical field. With the continued evolution in designing macromolecules-based nanoparticles for drug delivery, the combination approach of using important features of linear polymers with dendrimers has offered an advantageous and viable platform. Such nanostructures, which are commonly referred to as telodendrimers, are hybrids of linear polymers covalently linked with different dendrimer generations and backbones. There is considerable variety in selection from widely studied linear polymers and dendrimers, which can help tune the overall composition of the resulting hybrid structures. This review highlights the advances in articulating syntheses of these macromolecules, and the contributions these are making in facilitating therapeutic administration. Limited progress has been made in the design and synthesis of these hybrid macromolecules, and it is through an understanding of their physicochemical properties and aqueous self-assembly that one can expect to fully exploit their potential in drug delivery.

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Tunable Lipidoid‐Telodendrimer Hybrid Nanoparticles for Intracellular Protein Delivery in Brain Tumor Treatment

Cited by 17 publications

References 51 publications

Riboflavin-containing telodendrimer nanocarriers for efficient doxorubicin delivery: High loading capacity, increased stability, and improved anticancer efficacy

Riboflavin-containing telodendrimer nanocarriers for efficient doxorubicin delivery: High loading capacity, increased stability, and improved anticancer efficacy

Polycation-telodendrimer nanocomplexes for intracellular protein delivery

Telodendrimers: Promising Architectural Polymers for Drug Delivery

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