Molecular Self‐Assembly of a Homopolymer: An Alternative To Fabricate Drug‐Delivery Platforms for Cancer Therapy

Liu, Jinyao; Huang, Wei; Pang, Yan; Huang, Ping; Zhu, Xinyuan; Zhou, Yongfeng; Yan, Deyue

doi:10.1002/anie.201102280

Cited by 101 publications

(62 citation statements)

References 46 publications

(11 reference statements)

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“…[1][2][3] In the past a few decades, self-assembling materials with sophisticated multiple-level structures [4][5][6] have facilitated progresses in energy, 7,8 electronics, 9,10 optics, 11,12 disease diagnosing and clinical therapy. [13][14][15] However, manipulating the self-assembly of specifically designed building blocks to form predictable packing and ordered hierarchical structures remains a grand challenge. 16,17 Precise controls over the noncovalent or secondary interactions among the building blocks on different dimensions may be achieved through tuning primary chemical compositions.…”

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confidence: 99%

Manipulation of Self-Assembled Nanostructure Dimensions in Molecular Janus Particles

et al. 2016

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The ability to manipulate self-assembly of molecular building blocks is the key to achieving precise "bottom-up" fabrications of desired nanostructures. Herein, we report a rational design, facile synthesis, and self-assembly of a series of molecular Janus particles (MJPs) constructed by chemically linking α-Keggin-type polyoxometalate (POM) nanoclusters with functionalized polyhedral oligomeric silsesquioxane (POSS) cages. Diverse nanostructures were obtained by tuning secondary interactions among the building blocks and solvents via three factors: solvent polarity, surface functionality of POSS derivatives, and molecular topology. Self-assembled morphologies of KPOM-BPOSS (B denotes isobutyl groups) were found dependent on solvent polarity. In acetonitrile/water mixtures with a high dielectric constant, colloidal nanoparticles with nanophase-separated internal lamellar structures quickly formed, which gradually turned into one-dimensional nanobelt crystals upon aging, while stacked crystalline lamellae were dominantly observed in less polar methanol/chloroform solutions. When the crystallizable BPOSS was replaced with noncrystallizable cyclohexyl-functionalized CPOSS, the resulting KPOM-CPOSS also formed colloidal spheres; however, it failed to further evolve into crystalline nanobelt structures. In less polar solvents, KPOM-CPOSS crystallized into isolated two-dimensional nanosheets, which were composed of two inner crystalline layers of Keggin POM covered by two monolayers of amorphous CPOSS. In contrast, self-assembly of KPOM-2BPOSS was dominated by crystallization of the BPOSS cages, which was hardly sensitive to solvent polarity. The BPOSS cages formed the crystalline inner bilayer, sandwiched by two outer layers of Keggin POM clusters. These results illustrate a rational strategy to purposely fabricate self-assembled nanostructures with diverse dimensionality from MJPs with controlled molecular composition and topology.

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confidence: 99%

Manipulation of Self-Assembled Nanostructure Dimensions in Molecular Janus Particles

et al. 2016

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“…[12][13][14] As expected, the novel HPOXs without defined amphiphilic segments could self-assemble into nanoparticles, attributed to the inter-and intra-molecular multiple noncovalent interactions. 15,16 In particular, changing the surface functional groups and branched architecture of the HPOX led to the morphological transformation from spherical to bowl-shaped micelles. [17][18][19] Both oxime linkages and hydrogen bonds endowed the HPOXs with stimuli responsiveness.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and self-assembly of nonamphiphilic hyperbranched polyoximes

et al. 2012

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Nonamphiphilic hyperbranched polyoximes (HPOXs) were successfully synthesized by the polycondensation of trialdehyde and bis-aminooxy monomers with different molar feeding ratios.Various characterization techniques, such as 1D and 2D nuclear magnetic resonance (NMR), Fourier transform infrared spectroscopy (FTIR), and multi-detector gel permeation chromatography (GPC) were used to identify the highly branched structure of the HPOXs. Despite there being no amphiphilic block segments, HPOXs with a torispherical structure could self-assemble into nanoparticles in a mixed solution of dimethyl sulfoxide and H 2 O. Besides, the modulation of the degree of branching (DB) and the terminal groups resulted in the appearance of spherical and bowl-shaped morphologies due to the change of the intra-and inter-molecular interactions. Accordingly, dynamic light scattering (DLS), transmission electron microscopy (TEM), atomic force microscopy (AFM), scanning electron microscopy (SEM), fluorescence spectroscopy (FL) together with ultraviolet and visible spectrometery (UV-vis) were employed to unravel the tentative mechanism of the formation of the HPOX selfassemblies. Moreover, dynamic oxime linkages and hydrogen bonds endowed the HPOX nanoparticles with pH and thermal dual responsiveness, which was confirmed by TEM measurements. HPOXs are developed to offer a novel pathway for the design of nonamphiphilic self-assemblies with dual responsiveness.

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“…Terminal β-D-galactose (GAL) or N-acetylgalactosamine residues have been recognized as liver-specific targeting ligand for their binding affinity to the ASGP-Rs. [43][44] The desirable cystamine (BAC), methacrylic acid (MAA) and ammonium persulfate (APS, 98%) were purchased from Sigma Aldrich. 22,[33][34][35][36][37] Enhanced hepatic uptake was observed after incorporation of galactose residues or lactose moieties to proteins and drug-loaded polymers.…”

Section: Introductionmentioning

confidence: 99%

“…8,[27][28][29]44 Moreover, the intracellular GSH concentration is much higher in cancer cells, which has been an important feature for the development of anti-cancer drug delivery systems.In the present study, we have designed a multi-responsive and biodegradable nanogel-based drug delivery system with hepatocellular carcinoma targeting property via galactose functionalization. The nanogel exhibited redox, pH and temperature-responsive property, which can be adjusted by varying the monomer feeding ratio.…”

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Galactose-functionalized multi-responsive nanogels for hepatoma-targeted drug delivery

et al. 2015

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We report here a hepatoma-targeting multi-responsive biodegradable crosslinked nanogel, poly(6-O-vinyladipoyl-D-galactose-ss-N-vinylcaprolactam-ss-methacrylic acid) P(ODGal-VCL-MAA), using a combination of enzymatic transesterification and emulsion copolymerization for intracellular drug delivery. The nanogel exhibited redox, pH and temperature-responsive properties, which can be adjusted by varying the monomer feeding ratio. Furthermore, the volume phase transition temperature (VPTT) of the nanogels was close to body temperature and can result in rapid thermal gelation at 37 °C. Scanning electron microscopy also revealed that the P(ODGal-VCL-MAA) nanogel showed uniform spherical monodispersion. With pyrene as a probe, the fluorescence excitation spectra demonstrated nanogel degradation in response to glutathione (GSH). X-ray diffraction (XRD) showed an amorphous property of DOX within the nanogel, which was used in this study as a model anti-cancer drug. Drug-releasing characteristics of the nanogel were examined in vitro. The results showed multi-responsiveness of DOX release by the variation of environmental pH values, temperature or the availability of GSH, a biological reductase. An in vitro cytotoxicity assay showed a higher anti-tumor activity of the galactose-functionalized DOX-loaded nanogels against human hepatoma HepG2 cells, which was, at least in part, due to specific binding between the galactose segments and the asialoglycoprotein receptors (ASGP-Rs) in hepatic cells. Confocal laser scanning microscopy (CLSM) and flow cytometric profiles further confirmed elevated cellular uptake of DOX by the galactose-functionalised nanogels. Thus, we report here a multi-responsive P(ODGal-VCL-MAA) nanogel with a hepatoma-specific targeting ability for anti-cancer drug delivery.

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Molecular Self‐Assembly of a Homopolymer: An Alternative To Fabricate Drug‐Delivery Platforms for Cancer Therapy

Cited by 101 publications

References 46 publications

Manipulation of Self-Assembled Nanostructure Dimensions in Molecular Janus Particles

Manipulation of Self-Assembled Nanostructure Dimensions in Molecular Janus Particles

Synthesis and self-assembly of nonamphiphilic hyperbranched polyoximes

Galactose-functionalized multi-responsive nanogels for hepatoma-targeted drug delivery

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