Layer-by-Layer Nanoparticles with a pH-Sheddable Layer for <i>in Vivo</i> Targeting of Tumor Hypoxia

Poon, Zhiyong; Chang, Dongsook; Zhao, Xiaoyong; Hammond, Paula T.

doi:10.1021/nn200876f

Cited by 319 publications

(265 citation statements)

References 50 publications

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“…Layer by layer (LbL) assembled NPs are promising strategies for incorporating polyelectrolytes onto the surfaces of nanocarriers to provide enhanced stability, cellular uptake, regulation of drug release and targeting capabilities, [26][27][28][29] and have recently shown great value in gene and drug delivery. 28,[30][31][32] With multilayer alternative deposition of oppositely charged polyelectrolytes, drugloaded carriers and drug microcrystals could decrease initial drug burst release and sustain drug release.…”

Section: Introductionmentioning

confidence: 99%

Doxorubicin-loaded poly (lactic-co-glycolic acid) nanoparticles coated with chitosan/alginate by layer by layer technology for antitumor applications

Chai

Sun

et al. 2017

IJN

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Natural polyelectrolyte multilayers of chitosan (CHI) and alginate (ALG) were alternately deposited on doxorubicin (DOX)-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) with layer by layer self-assembly to control drug release for antitumor activity. Numerous factors which influenced the multilayer growth on nano-colloidal particles were studied: polyelectrolyte concentration, NaCl concentration and temperature. Then the growth regime of the CHI/ALG multilayers was elucidated. The coated NPs were characterized by transmission electron microscopy, atomic force microscopy, X-ray diffraction and a zeta potential analyzer. In vitro studies demonstrated an undesirable initial burst release of DOX-loaded PLGA NPs (DOX-PLGA NPs), which was relieved from 55.12% to 5.78% through the use of the layer by layer technique. The release of DOX increased more than 40% as the pH of media decreased from 7.4 to 5.0. More importantly, DOX-PLGA (CHI/ALG) 3 NPs had superior in vivo tumor inhibition rates at 83.17% and decreased toxicity, compared with DOX-PLGA NPs and DOX in solution. Thus, the presently formulated PLGA-polyelectrolyte NPs have strong potential applications for numerous controlled anticancer drug release applications.

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Section: Introductionmentioning

confidence: 99%

Doxorubicin-loaded poly (lactic-co-glycolic acid) nanoparticles coated with chitosan/alginate by layer by layer technology for antitumor applications

Chai

Sun

et al. 2017

IJN

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“…When apolipoprotein B small interfering RNA as a model drug was used, apolipoprotein B mRNA level in the liver tissue was markedly reduced. Poon et al 56 developed LbL nanoparticles with appropriately designed layered structures for targeting of tumor hypoxia. The capsules were coated with a stealth layer of poly(ethylene glycol) to suppress nonspecific cellular uptake of positively charged LbL nanoparticles.…”

Section: Biomedical Applicationsmentioning

confidence: 99%

Forming nanomaterials as layered functional structures toward materials nanoarchitectonics

et al. 2012

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Although progress in nanotechnology is anticipated to stimulate the development of innovative materials, the areas of nanotechnology and materials science are somehow separated with little common ground in current technologies. Nanotechnology has some analytical aspects that are beneficial mainly to the nanoscopic sciences at the atom or molecular levels. Experience of these advanced techniques has only been applied in synthetic approaches to macroscopic materials in rather immature level. Forming nanomaterials into hierarchic and organized structures is a rational way of preparing advanced functional materials. Recently, one of us coined the term materials' nanoarchitectonics to express this innovation. This review focuses on recent research to develop functional materials by forming nanomaterials into organized structures, especially in well-ordered layered structural motifs. This layered nanoarchitectonics can be achieved by using the versatile technology of layer-by-layer assembly. Reassembly of bulk materials into novel layered structures through layered nanoarchitectonics has created many innovative functional materials in a wide variety of fields as can be seen in ferromagnetic nanosheets, sensors, flame-retardant coatings, transparent conductors, electrodes and transistors, walking devices, drug release surfaces, targeting drug carriers and cell culturing.

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“…These obstacles existing in the body could considerably prevent nanomedicine from reaching its targets in a sufficient drug concentration (7,8). To overcome these barriers, a variety of strategies have been envisioned (9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Despite great advances, these strategies have mainly focused on one or a few biological barriers and led to suboptimal therapeutic effect.…”

mentioning

confidence: 99%

Stimuli-responsive clustered nanoparticles for improved tumor penetration and therapeutic efficacy

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

647

406

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A principal goal of cancer nanomedicine is to deliver therapeutics effectively to cancer cells within solid tumors. However, there are a series of biological barriers that impede nanomedicine from reaching target cells. Here, we report a stimuli-responsive clustered nanoparticle to systematically overcome these multiple barriers by sequentially responding to the endogenous attributes of the tumor microenvironment. The smart polymeric clustered nanoparticle (iCluster) has an initial size of ∼100 nm, which is favorable for long blood circulation and high propensity of extravasation through tumor vascular fenestrations. Once iCluster accumulates at tumor sites, the intrinsic tumor extracellular acidity would trigger the discharge of platinum prodrug-conjugated poly(amidoamine) dendrimers (diameter ∼5 nm). Such a structural alteration greatly facilitates tumor penetration and cell internalization of the therapeutics. The internalized dendrimer prodrugs are further reduced intracellularly to release cisplatin to kill cancer cells. The superior in vivo antitumor activities of iCluster are validated in varying intractable tumor models including poorly permeable pancreatic cancer, drug-resistant cancer, and metastatic cancer, demonstrating its versatility and broad applicability.nanomedicine | particle size | tumor penetration | tumor extracellular pH | stimuli responsive

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Layer-by-Layer Nanoparticles with a pH-Sheddable Layer for in Vivo Targeting of Tumor Hypoxia

Cited by 319 publications

References 50 publications

Doxorubicin-loaded poly (lactic-co-glycolic acid) nanoparticles coated with chitosan/alginate by layer by layer technology for antitumor applications

Doxorubicin-loaded poly (lactic-co-glycolic acid) nanoparticles coated with chitosan/alginate by layer by layer technology for antitumor applications

Forming nanomaterials as layered functional structures toward materials nanoarchitectonics

Stimuli-responsive clustered nanoparticles for improved tumor penetration and therapeutic efficacy

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