pH-sensitive degradable nanoparticles for highly efficient intracellular delivery of exogenous protein

Xu, Dan; Wu, Fei; Chen, Yinghui; Wei, Liangming; Yuan, Weien

doi:10.2147/ijn.s47701

Cited by 7 publications

(3 citation statements)

References 35 publications

(32 reference statements)

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“…Moreover, drugs have been targeted to early endosomes by exploiting the low pH of the endosomal network or by conjugation to ligands that are internalised via receptor-mediated processes (reviewed in Rajendran et al, 2010). As an alternative to conjugation, the use of nanoparticles to encapsulate a drug of interest provides greater flexibility due to the possibility of functionalising the exterior of the particle with targeting motifs, or the use of pH-sensitive polymers (Friedman et al, 2013;Xu et al, 2013). A focus on the method of drug delivery, rather than on the design of novel small molecule allosteric compounds, may provide a much quicker and ultimately more efficient route to the generation of selective AC inhibitors.…”

Section: Selectively Inhibit Acs Within Sub-cellular Microdomainsmentioning

confidence: 99%

Adenylyl cyclase signalling complexes – Pharmacological challenges and opportunities

Halls

Cooper

2017

Pharmacology & Therapeutics

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Section: Selectively Inhibit Acs Within Sub-cellular Microdomainsmentioning

confidence: 99%

Adenylyl cyclase signalling complexes – Pharmacological challenges and opportunities

Halls

Cooper

2017

Pharmacology & Therapeutics

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“…In vitro experiments showed the prepared NPs were nontoxic to both NIH 3T3 fibroblasts and HepG2 cells. Xu et al 95 prepared pH-sensitive NPs with potential as a protein delivery system. The core contained glassy NPs formed from cross-linked dextran that was pH-sensitive and the protein was encapsulated inside.…”

Section: Ph-sensitive Nanocarriersmentioning

confidence: 99%

“…They display good encapsulation capability and their rigid surfaces allow controlled functionalization. 95 Some inorganic NPs can be used as pH-sensitive functional materials when combined with organic components such as chitosan, 104 polydopamine, 105 poly(acrylic acid), 106 etc.…”

Section: Ph-sensitive Nanocarriersmentioning

confidence: 99%

pH‐Sensitive stimulus‐responsive nanocarriers for targeted delivery of therapeutic agents

Karimi

Eslami

Zangabad

et al. 2016

WIREs Nanomed Nanobiotechnol

198

105

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In recent years miscellaneous smart micro/nanosystems that respond to various exogenous/endogenous stimuli including temperature, magnetic/electric field, mechanical force, ultrasound/light irradiation, redox potentials, and biomolecule concentration have been developed for targeted delivery and release of encapsulated therapeutic agents such as drugs, genes, proteins, and metal ions specifically at their required site of action. Owing to physiological differences between malignant and normal cells, or between tumors and normal tissues, pH-sensitive nanosystems represent promising smart delivery vehicles for transport and delivery of anticancer agents. Furthermore, pH-sensitive systems possess applications in delivery of metal ions and biomolecules such as proteins, insulin, etc., as well as co-delivery of cargos, dual pH-sensitive nanocarriers, dual/multi stimuli-responsive nanosystems, and even in the search for new solutions for therapy of diseases such as Alzheimer’s. In order to design an optimized system, it is necessary to understand the various pH-responsive micro/nanoparticles and the different mechanisms of pH-sensitive drug release. This should be accompanied by an assessment of the theoretical and practical challenges in the design and use of these carriers.

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Chitosan Nanoparticles for Nuclear Targeting: The Effect of Nanoparticle Size and Nuclear Localization Sequence Density

et al. 2015

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Many recently discovered therapeutic proteins exert their main function in the nucleus, thus requiring both efficient uptake and correct intracellular targeting. Chitosan nanoparticles (NPs) have attracted interest as protein delivery vehicles due to their biocompatibility and ability to escape the endosomes offering high potential for nuclear delivery. Molecular entry into the nucleus occurs through the nuclear pore complexes, the efficiency of which is dependent on NP size and the presence of nuclear localization sequence (NLS). Chitosan nanoparticles of different sizes (S-NPs ≈ 25 nm; L-NP ≈ 150 nm) were formulated, and they were modified with different densities of the octapeptide NLS CPKKKRKV (S-NPs, 0.25, 0.5, 2.0 NLS/nm(2); L-NPs, 0.6, 0.9, 2 NLS/nm(2)). Unmodified and NLS-tagged NPs were evaluated for their protein loading capacity, extent of cell association, cell uptake, cell surface binding, and finally nuclear delivery efficiency in L929 fibroblasts. To avoid errors generated with cell fractionation and nuclear isolation protocols, nuclear delivery was assessed in intact cells utilizing Förster resonance energy transfer (FRET) fluorometry and microscopy. Although L-NPs showed ≈10-fold increase in protein loading per NP when compared to S-NPs, due to higher cell association and uptake S-NPs showed superior protein delivery. NLS exerts a size and density dependent effect on nanoparticle uptake and surface binding, with a general reduction in NP cell surface binding and an increase in cell uptake with the increase in NLS density (up to 8.4-fold increase in uptake of High-NLS-L-NPs (2 NLS/nm(2)) compared to unmodified L-NPs). However, for nuclear delivery, unmodified S-NPs show higher nuclear localization rates when compared to NLS modified NPs (up to 5-fold by FRET microscopy). For L-NPs an intermediate NLS density (0.9 NLS/nm(2)) seems to provide highest nuclear localization (3.7-fold increase in nuclear delivery compared to High-NLS-L-NPs). Results indicate that a higher NLS density does not result in maximum protein nuclear localization and that a universal optimal density for NPs of different sizes does not exist.

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pH-sensitive degradable nanoparticles for highly efficient intracellular delivery of exogenous protein

Cited by 7 publications

References 35 publications

Adenylyl cyclase signalling complexes – Pharmacological challenges and opportunities

Adenylyl cyclase signalling complexes – Pharmacological challenges and opportunities

pH‐Sensitive stimulus‐responsive nanocarriers for targeted delivery of therapeutic agents

Chitosan Nanoparticles for Nuclear Targeting: The Effect of Nanoparticle Size and Nuclear Localization Sequence Density

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