Micelle-like Nanoparticles Research Articles

Self-assembly of cytotoxic peptide conjugated poly(β-amino ester)s for synergistic cancer chemotherapy.

Nanotechnology has played an important role in cancer therapy due to the potential advantages of nano-drugs including enhanced accumulation in the tumor sites, improved pharmacokinetics and minimized systemic toxicity in vivo. Self-assembled peptides can improve the cellular internalization of peptides effectively through the endocytosis pathway for enhanced bioavailability. Herein, cytotoxic peptide (KLAKLAK)2 (named KLAK) conjugated poly(β-amino ester)s (PAE-KLAK) were synthesized by Michael-type addition. The copolymers could self-assemble into micelle-like nanoparticles with pH-sensitive properties, which were measured by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The endocytosis pathway, mitochondria-regulated apoptosis and enhanced cytotoxicity of P2-KLAK micelles were proved by lysosome colocalization, JC-1 assay and CCK-8 assay in human breast cancer cells (MCF-7 cells), respectively. The cancer cell killing effect of P2-KLAK micelles was higher than that of free KLAK, which could be attributed to the efficient internalization into cells via an endocytosis pathway and a subsequent disruption of mitochondria in cells. Encapsulation of anti-cancer drug doxorubicin (DOX) into P2-KLAK micelles realized the co-delivery of the chemotherapeutic drug and the peptide drug with acid-triggered release in cells. The treatment efficacy of DOX-loaded P2-KLAK micelles was higher than that of DOX-loaded P2 micelles and blank P2-KLAK micelles, indicating their synergistic ability to kill MCF-7 cells. Finally, In vivo tumor imaging and growth inhibition were evaluated in MCF-7 cell-xenografted nude mice, demonstrating that DOX-loaded P2-KLAK micelles could inhibit tumor growth effectively with a one order magnitude lower injection amount of DOX, which was attributed to the specific accumulation in tumor sites, efficient cellular entry and controlled intracellular release of therapeutic drugs.

Luminescent nanoparticles with lanthanide-containing poly(ethylene glycol)-Poly(ε-caprolactone) block copolymers.

Lanthanide-containing nanoparticles have attracted much attention due to their unique optical properties and potential in nanotechnological applications. An amphiphilic block copolymer of poly(ethylene glycol)-b-poly(ε-caprolactone) methyl ether (mPEG-PCL) was functionalized with a dipicolinic acid (dpa) moiety and coordinated to lanthanide ions to afford [Ln(dpa-PCL-PEG-OCH3)3](HNEt3)3 (Ln = Eu(3+), Tb(3+)). Micelle-like nanoparticles of dpa-PCL-PEG-OCH3 macroligand and metal-centered polymers were prepared by solvent displacement methods. Dynamic light scattering analysis (DLS) and cryogenic transmission electron microscopy images confirmed the presence of solid sphere (<47 nm in diameter) and vesicle (>47 nm in diameter) morphologies. The viability and stability of the lanthanide complexes in micelle-like nanoparticles was explored by DLS and luminescence spectroscopy, and found to be stable for several weeks.

Star-shaped polycaprolactone-polyethyleneglycol copolymer micelle-like nanoparticles for picropodophyllin delivery.

The purpose of this work was to develop a novel picropodophyllin-loaded micelle-like nanoparticle with a biodegradable amphiphilic star-shaped polycaprolactone-polyethyleneglycol copolymer (S-PCL-PEG). S-PCL-PEG was synthesized using star-shaped polycaprolactone (S-PCL) as a hydrophobic block and monomethoxy polyethyleneglycol (PEG) as a hydrophilic block and characterized by 1H-NMR. It was confirmed by the pyrene fluorescence probe method that the obtained S-PCL-PEG could form micelles through self-assembly in aqueous media. In addition, picropodophyllin (PPP), a hydrophobic anticancer drug, could be entrapped in the hydrophobic inner core of the micelles using the thin film hydration method, forming PPP-loaded micelle-like nanoparticles (PPP-NPs). PPP-NPs had a high encapsulation efficiency of greater than 90%, an average size of 90-110 nm with a symmetrical monodisperse distribution and a zeta potential of -18 mV. Additionally, in vitro release tests showed that approximately 70% of the drug was released from PPP-NPs into PBS (pH 7.4) containing 0.2% Tween 80 at 37 degrees C for 96 h, and the drug release data fit well to the Higuchi equation. Furthermore, an in vitro tumor cell growth inhibition assay showed that the IC50 values of the PPP solution and PPP-NPs against SMMC7721 liver cancer cell lines were 0.4 microg/ml and 0.2 microg/ml respectively, which indicated that the cytotoxicity of PPP-NPs against tumor cells was greater than that of the PPP solution. In conclusion, S-PCL-PEG micelle-like nanoparticles loaded with PPP have a promising future for administration by injection.

Pluronic-poly[alpha-(4-aminobutyl)-1-glycolic acid] polymeric micelle-like nanoparticles as carrier for drug delivery.

Pluronic-poly[alpha-(4-aminobutyl)-1-glycolic acid] (Pluronic-PAGA) with different types of Pluronic, the different molecule weight of PAGA, and the different molar ratios of Pluronic to PAGA were synthesized. These materials were bio-degradable, amphiphilic, could be degraded into non-toxic small molecules and could be used to carry drugs. 5-Fluorouracil (5-Fu) loaded Pluronic-PAGA micelle-like nanoparticles (5-Fu loaded P-PAGA NPs) were prepared by a simple self-assembly method, and characterized by dynamic light scattering, transmission electron microscope. The degradation and release characteristics have also been studied in this paper. With the time passing, the 5-Fu loaded P-PAGA NPs degraded into smaller ones with the similar characteristics of the original NPs. Both the types of Pluronic and the molecule weight of the PAGA affected the releasing progresses. It was found that 5-Fu loaded P-PAGA NPs exhibited high growth inhibitory effect on human gastric cancer cells by MTT assay. The cellular uptake of Rhodamine B loaded P-PAGA NPs was higher than free Rhodamine B. This study suggested that the Pluronic-PAGA with acceptable drug entrapment efficiencies, drug loading efficiencies and tunable release profiles could offer an alternative carrier for 5-Fu delivery and have the potential for the delivery of other anti-tumour drug.

Self-Assembling Micelle-like Nanoparticles with Detachable Envelopes for Enhanced Delivery of Nucleic Acid Therapeutics

In spite of the great potential of nucleic acids as therapeutic agents, the clinical application of nucleic acid therapeutics requires the development of effective systemic delivery strategies. In an effort to develop effective nucleic acid delivery systems suitable for clinical application, we previously reported a self-assembling micelle-like nanoparticle that was based on phospholipid-polyethylenimine conjugates, i.e., "micelle-like nanoparticles" (MNPs). In this study, we aimed to improve the system by enhancing the efficiency of intracellular delivery of the payload via pH-responsive detachment of the monolayer envelope and release of the nucleic acid therapeutics upon reaching the target tissues with an acidic pH, e.g., tumors. The acid-cleavable phospholipid-polyethylenimine conjugate was synthesized via hydrazone bond, and acid-cleavable MNPs were then prepared and characterized as before. We evaluated the acid-cleavable MNP construct for in vitro and in vivo nucleic acid delivery efficiency using cultured tumor cells and tumor-bearing mice. The acid-cleavable nanocarrier showed an enhanced cellular delivery at pH 6.5 as compared to pH 7.4, whereas the noncleavable nanocarrier did not show any differences. Tail vein injections also led to enhanced intracellular uptake of the acid-cleavable nanocarrier compared to the noncleavable nanocarrier into tumor cells of tumor-bearing mice although no significant difference was observed in total tumor accumulation.

Self-Assembly of Amphiphilic Plasmonic Micelle-Like Nanoparticles in Selective Solvents

Amphiphilic plasmonic micelle-like nanoparticles (APMNs) composed of gold nanoparticles (AuNPs) and amphiphilic block copolymers (BCPs) structurally resemble polymer micelles with well-defined architectures and chemistry. The APMNs can be potentially considered as a prototype for modeling a higher-level self-assembly of micelles. The understanding of such secondary self-assembly is of particular importance for the bottom-up design of new hierarchical nanostructures. This article describes the self-assembly, modeling, and applications of APMN assemblies in selective solvents. In a mixture of water/tetrahydrofuran, APMNs assembled into various superstructures, including unimolecular micelles, clusters with controlled number of APMNs, and vesicles, depending on the lengths of polymer tethers and the sizes of AuNP cores. The delicate interplay of entropy and enthalpy contributions to the overall free energy associated with the assembly process, which is strongly dependent on the spherical architecture of APMNs, yields an assembly diagram that is different from the assembly of linear BCPs. Our experimental and computational studies suggested that the morphologies of assemblies were largely determined by the deformability of the effective nanoparticles (that is, nanoparticles together with tethered chains as a whole). The assemblies of APMNs resulted in strong absorption in near-infrared range due to the remarkable plasmonic coupling of Au cores, thus facilitating their biomedical applications in bioimaging and photothermal therapy of cancer.

Oxidation-Accelerated Hydrolysis of the Ortho Ester-Containing Acid-Labile Polymers.

We report a versatile method to tune the hydrolysis of the ortho ester-containing block copolymers by covalently incorporating oxidation-sensitive phenylboronic ester units. A series of block copolymers which contain a polyethylene glycol (PEG) block and a hydrophobic segment composed of different amounts of pendent ortho ester and phenylboronic ester groups were synthesized. These copolymers can self-assemble into narrowly dispersed micelle-like nanoparticles in phosphate buffer. The kinetics of phenylboronic ester oxidation and ortho ester hydrolysis in the nanoparticles were studied at different pH and H2O2 concentration. The results indicated that the phenylboronic ester oxidation rate was faster than the ortho ester hydrolysis rate at neutral pH, and both processes were accelerated with increasing H2O2 concentration. Nanoparticles which are extremely sensitive to the biorelevant concentration of H2O2 (50 μM) at pH 7.4 were obtained, suggesting great promise for inflammation-specific drug delivery.

Synthesis and evaluation of methionine and folate co-decorated chitosan self-assembly polymeric micelles as a potential hydrophobic drug-delivery system

In this study, an amphiphilic copolymer folate-succinyl-methionine-chitosan-octyl (FSMCO) was successfully synthesized step by step for self-assembling polymeric micelles. The copolymers formed micelle-like nanoparticles by their amphiphilic characteristics and structures were examined by UV-Vis absorption and Fourier transform spectroscopy. The sizes of blank and ICG derivative-loaded micelles measured by dynamic light scattering were about 170 and 140 nm, respectively, which were spherical in shape with an average zeta potential of −10 mV. Further studies on the stability showed that the micellar solutions maintain their sizes at room temperature for 1 month without distinct aggregation or dissociation. ICG derivative was much better photostable after being entrapped by the new carrier. The prepared FSMCO micelles displayed a good drug loading content (11.7%), entrapment efficiency (66.5%) and sustained release rate for the model drug fluorescein. The copolymers demonstrated weeny cytotoxicity toward Bel-7402, L02 and A549 cells when incubated for 2 d. Ligands modified micelles endowed preferable cell targeting capability and beautiful cell inhibition of HCPT-FSMCO on Bel-7402 tumor cells. This kind of polymeric micelles may be a promising nanovehicle in delivering near-infrared dyes for tumors imaging and chemotherapeutic drugs for cancer therapeutics.

Sequential thermo-induced self-gelation and acid-triggered self-release process of drug-conjugated nanoparticles: a strategy for the sustained and controlled drug delivery to tumors.

A novel strategy was purposed to sustainedly deliver drug-loaded nanoparticles (NPs) to tumor sites and further enhance intracellular drug release. NPs with the ability of sequential self-gelation and self-release in response to a tumor-specific microenvironment were developed, which involved the conjugation of doxorubicin (DOX) on a thermosensitive amphiphilic copolymer (poly(ε-caprolactone)-b-poly(ethylene glycol)-b-poly(ε-caprolactone), PCEC) via acid-cleavable hydrazone linkages. The conjugate (PCEC-co-DOX) can self-assemble into micelle-like NPs in water. Moreover, the freeze-dried PCEC-co-DOX NP powder with good dispersibility in water can easily be constructed into an injectable NP aqueous dispersion at ambient temperature, making it convenient for storage and clinical applications. After injection, the dispersion can in situ thermosensitively self-gelate, anchoring large amounts of NPs at the tumor site. Subsequently, the formed NP self-supported gel can sustainedly release NPs themselves in an acidic tumor microenvironment. The released DOX-co-PCEC NPs were taken up by tumor cells and finally realized in intracellular drug release by the acid-triggered cleavage of the hydrazone bond. Compared with the repeated injection of free DOX, a single peritumoral injection of DOX-co-PCEC NP aqueous dispersion achieved a similar tumor inhibition effect but exhibited lower systemic toxicity. In vivo biodistribution studies indicated that DOX delivered by the DOX-co-PCEC NP hydrogel accumulated mainly in tumor tissue rather than in healthy tissue in mice treated with a single peritumoral injection. These results suggest that the design presented here provides a promising nanomedicine platform for cancer therapy.

Flt1 peptide–hyaluronate conjugate micelle-like nanoparticles encapsulating genistein for the treatment of ocular neovascularization

Flt1 peptide of GNQWFI is an antagonistic peptide for vascular endothelial growth factor receptor 1 (VEGFR1 or Flt1). In this work, Flt1 peptide–hyaluronate (HA) conjugates were successfully synthesized and the resulting micelle-like nanoparticles were exploited to encapsulate genistein, an inhibitor of tyrosine-specific protein kinases, for the treatment of ocular neovascularization. The mean diameter of genistein-loaded Flt1 peptide–HA conjugate micelles was measured to be 172.0±18.7nm, with a drug-loading efficiency of 40–50%. In vitro release tests of genistein from the genistein-loaded Flt1 peptide–HA conjugate micelles exhibited the controlled release for longer than 24h. In vitro biological activity of genistein/Flt1 peptide–HA micelles was corroborated from the synergistic anti-proliferation of human umbilical vein endothelial cells (HUVECs). Furthermore, we could confirm the anti-angiogenic effect of genistein/Flt1 peptide–HA micelles from the statistically significant suppression of corneal neovascularization in silver nitrate cauterized corneas of SD rats. The retinal vascular hyperpermeability was also drastically reduced by the treatment in diabetic retinopathy model rats.

Gold half-shell coated hyaluronic acid-doxorubicin conjugate micelles for theranostic applications

Theranostic systems have been widely investigated for application in the diagnostic therapy of cancers. In this work, hyaluronic acid (HA)-doxorubicin (DOX) conjugate was successfully synthesized by the amide bond formation between amine groups of DOX and carboxylic groups of HA activated with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysulfosuccinimide. The 1H nuclear magnetic resonance (NMR) and gel permeation chromatographic (GPC) analyses confirmed the successful synthesis of HA-DOX conjugates. HA-DOX conjugates self-assembled to micelle-like nanoparticles in aqueous solution. In vitro anti-proliferation tests of cancer cells confirmed the anti-tumor effect of HA-DOX conjugate micelles. For further application, the micelles were coated with a gold (Au) half-shell by the thermal vapor deposition method, which might contribute to prolonging the residence time in the body with a versatile surface modification on the Au surface. TEM analysis confirmed the successful Au coating on HA-DOX conjugate micelles with a thickness of 15 nm. The Au half-shell-coated HADOX conjugate micelles might be successfully exploited for cancer theranostic applications such as chemotherapy, hyperthermia, and bioimaging. Open image in new window

P-Glycoprotein Silencing with siRNA Delivered by Dope-Modified Pei Overcomes Doxorubicin Resistance in Breast Cancer Cells

Multidrug resistance (MDR) mediated by overexpression of drug efflux transporters such as P-glycoprotein (P-gp), is a major problem, limiting successful chemotherapy of breast cancer. The use of siRNA to inhibit P-gp expression in MDR tumors is an attractive strategy to improve the effectiveness of anticancer drugs. We have synthesized a novel conjugate between a phospholipid (dioleoylphosphatidylethanolamine) and polyethylenimine (PEI) for siRNA delivery, for the purpose of silencing P-gp to overcome doxorubicin resistance in MCF-7 human breast cancer cells. The dioleoylphosphatidylethanolamine-PEI conjugate enhanced the transfection efficacy of low-molecular-weight PEI, which was otherwise totally ineffective. In addition, the polyethylene glycol/lipid coating of the new complexes gave rise to small micelle-like nanoparticles with improved biocompatibility properties. Both coated and noncoated formulations delivered P-gp-specific siRNA to MDR cells. The combination of doxorubicin and P-gp silencing formulations led to a twofold increase of doxorubicin uptake and a significant improvement of the therapeutic effect of doxorubicin in resistant cells.

Anti-Flt1 peptide – Hyaluronate conjugate for the treatment of retinal neovascularization and diabetic retinopathy

Anti-angiogenic therapeutics has been investigated extensively for the treatment of retinal and choroidal vascular diseases, and diabetic retinopathy. Anti-Flt1 peptide of GNQWFI is an antagonistic peptide for vascular endothelial growth factor receptor 1 (VEGFR1 or Flt1) inhibiting VEGFR1-mediated endothelial cell migration and tube formation. In this work, anti-Flt1 peptide (GGNQWFI) was chemically conjugated to tetra-n-butyl ammonium modified hyaluronate (HA-TBA) via amide bond formation in dimethyl sulfoxide (DMSO) using benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP). The resulting HA – GGNQWFI conjugate self-assembled to form micelle-like nanoparticles in aqueous solution, as confirmed and characterized by transmission electron microscopy (TEM). According to in vitro biological activity tests, HA – GGNQWFI conjugate exhibited a dose-dependent inhibition effect on the binding of Flt1-Fc to VEGF165 coated on the well. Furthermore, anti-Flt1 peptide – HA conjugate effectively inhibited retinal choroidal neovascularization (CNV) in laser induced CNV model rats. The retinal vascular permeability and the deformation of retinal vascular structure were also significantly reduced in diabetic retinopathy model rats after treatment with anti-Flt1 peptide – HA conjugate. Pharmacokinetic analysis confirmed the increased mean residence time of anti-Flt1 peptide after conjugation to HA longer than 2 weeks.

Phospholipid–polyethylenimine conjugate-based micelle-like nanoparticles for siRNA delivery

Gene silencing using small interfering RNA (siRNA) is a promising therapeutic strategy for the treatment of various diseases, in particular, cancer. Recently, our group reported on a novel gene carrier, the micelle-like nanoparticle (MNP), based on the combination of a covalent conjugate of phospholipid and polyethylenimine (PLPEI) with polyethylene glycol (PEG) and lipids. These long-circulating MNPs loaded with plasmid DNA-mediated gene expression in distal tumors after systemic administration in vivo. In the current study, we investigated the potential of MNPs for siRNA delivery. MNPs were prepared by condensing siRNA with PLPEI at a nitrogen/phosphate ratio of 10, where the binding of siRNA is complete. The addition of a PEG/lipid coating to the PLPEI complexes generated particles with sizes of ca. 200 nm and a neutral surface charge compared with positively charged PLPEI polyplexes without the additional coating. MNPs protected the loaded siRNA against enzymatic digestion and enhanced the cellular uptake of the siRNA payload. MNPs carrying green fluorescent protein (GFP)-targeted siRNA effectively downregulated the gene in cells that stably express GFP. Finally, MNPs were non-toxic at a wide range of concentrations and for different cell lines.

Micelle-like nanoparticles of block copolymer poly(ethylene oxide)- block-poly(methacrylic acid) incorporating fluorescently substituted metallacarboranes designed as HIV protease inhibitor interaction probes

We prepared nanoparticles differing in morphology from double-hydrophilic block copolymer poly(ethylene oxide)- block-poly(methacrylic acid), PEO–PMA, and two types of fluorescein–[3-cobalt(III) bis(1,2-dicarbollide)] conjugates, GB176 and GB179, in alkaline buffer. GB176 molecule consists of fluorescein attached to the metallacarborane anion. In GB179 molecule, the fluorescein moiety connects two metallacarborane anions. The self-assembly is based on the unusual interaction of metallacarborane clusters with PEO blocks which form insoluble micellar cores. The GB176 containing nanoparticles are loose and irregular, while the GB179 ones are rigid and spherical. The structure of nanoparticles depends to some extent on a procedure of preparation. The micelles were studied by static and dynamic light scattering, fluorometry and atomic force microscopy. Since the metallacarborane conjugates act as potent inhibitors of HIV protease, the presented system is important from the point of view of drug delivery.

Amphiphilic Block Copolymers Bearing Ortho Ester Side‐Chains: pH‐Dependent Hydrolysis and Self‐Assembly in Water

A new type of pH-responsive block copolymer nanoparticle has been synthesized and characterized. The amphiphilic diblock copolymer, PEG-b-PMYM, contains acid-labile ortho ester side-chains in the hydrophobic block and can self-assemble into micelle-like nanoparticles in water at neutral pH. Hydrolysis of the ortho ester side-chains follows a distinct exocyclic mechanism and shows pH-dependent kinetics, which triggers changes in nanoparticle size and morphology. The nanoparticles have been found to be non-toxic to cells in vitro. The ability to tune the size and morphology of biocompatible block copolymer nanoparticles by controlling the pH-sensitive side-chain hydrolysis represents a unique approach that may be exploited to improve the efficacy of nanometer-scale drug delivery.

Organic support for ethylene polymerization based on the self-assembly in heptane of end-functionalized polyisoprene

In this work, we report how micellar structures obtained by the self-assembly in heptane of polyisoprene end-capped with a hindered tertiary alcohol moiety (PI-φ2OH) can be efficiently used as organic supports for olefin polymerization single-site catalysts. PI-φ2OH has been synthesized by end-capping living polyisoprenyllithium with an excess of benzophenone. Dynamic light scattering analysis indicates a self-assembly of PI-φ2OH in heptane, a good solvent for polyisoprene and a poor one for the polar end-group. The so-formed micelle-like nanoparticles, composed of a di-phenyl alcohol group core and a polyisoprene corona were used as organic supports for catalytic system composed of aluminic activators, trimethylaluminium (TMA) or methylaluminoxane (MAO), and metallocene or post-metallocene catalysts, to produce micrometric polyethylene beads.

Hybrid inorganic–organic proton conducting membranes based on Nafion, SiO 2 and triethylammonium trifluoromethanesulfonate ionic liquid

New hybrid inorganic–organic nanocomposite proton conducting membranes based on Nafion, SiO 2 and triethylammonium trifluoromethanesulfonate (TEATF), a protic ionic liquid, were prepared in two steps. First, various [Nafion/(SiO 2) ψ ] membranes with a SiO 2 weight percentage ranging from 0 to 15 wt.% were prepared by a solvent-casting protocol from DMF solutions. Second, the resulting hybrid membranes were neutralized with triethylammine (TEA) and then impregnated with triethylammonium trifluoromethanesulfonate (TEATF). The structure of the bulk hybrid materials and the interactions occurring between their components were investigated by vibrational spectroscopy (FT-IR ATR and FT-Raman). These latter studies allowed to determine that: (a) the fluorocarbon domains of Nafion consist of a mixture of helical chains with 10 3 and 15 7 helical conformations; (b) interactions take place between the components of the hydrophilic domains, which give rise to micelle-like nanoparticles where a SiO 2 core is covered by a shell of solvating TEATF molecules. The thermal, mechanical and electrical properties of the proposed materials were investigated by thermogravimetry (TG) and differential scanning calorimetry (DSC) measurements, by dynamical mechanical analyses (DMA) and by broadband dielectric spectroscopy (BDS), respectively. The electric measurements indicated that [Nafion/(SiO 2) ψ (TEA)] 3.67/(TEATF) 1.2 exhibits a σ dc of 4.7 × 10 −3 S cm −1 at T = 105 °C and a SRC of 5 < T < 135 °C. These results classified this membrane as a very promising material for application in fuel cells.

Acid-Sensitive Polymeric Micelles Based on Thermoresponsive Block Copolymers with Pendent Cyclic Orthoester Groups

An orthoester-containing monomer, trans-N-(2-ethoxy-1,3-dioxan-5-yl)acrylamide (tNEA), was synthesized. Atom transfer radical polymerization of tNEA using a poly(ethylene glycol) (PEG) macroinitiator afforded three acid-labile thermoresponsive block copolymers: PEG-b-PtNEA27, PEG-b-PtNEA56, and PEG-b-PtNEA73. These block copolymers are water-soluble at low temperatures (<13 °C). Thermally induced phase transition behaviors, including the critical aggregation temperatures (CATs), of these polymers were investigated by light scattering and 1H NMR. The results indicated that the longer the PtNEA chain length, the lower the CAT. Upon heating above the CATs, all the three polymers underwent a phase transition and formed polymeric micelles or micelle-like nanoparticles with PEG as the shell and PtNEA block as the core. Both the sizes and morphologies of the micelles were found to be affected by the heating rate and the salt concentration in the buffers. The micelles, formed through a fast heating procedure in the buffer with a relatively high salt concentration, have a smaller size and a more compacted structure. pH-dependent destabilization of the polymeric micelles prepared from PEG-b-PtNEA73 was studied by using light scattering and Nile Red fluorescence. The results demonstrated that hydrophobic Nile Red could be loaded in the micelles that were stable at pH 7.4, but destabilized in mildly acidic media. The dissociation of the micelles and the subsequent release of Nile Red were induced by the acid-triggered hydrolysis of the orthoester groups, which was proved by the 1H NMR spectra.

Iron Tris(bipyridine)-Centered Poly(ethylene glycol)-Poly(lactic acid) Star Block Copolymers

Block copolymers incorporating biocompatible poly(ethylene glycol) (PEG) and poly(lactide) (PLA) polymers and labile metal complexes can serve as stimuli responsive biomaterials. Bipyridine-centered PEG-PLA materials were prepared via ring opening polymerization of ethylene oxide and lactide (d,l and l). Macroligands and their iron complexes [Fe{bpy(PEG-PLA)2}3]Cl2 were characterized by gel permeation chromatography, 1H NMR, and UV−vis spectroscopy. Solvent and counterion effects were also explored by UV−vis spectroscopy. Extinction coefficients drop 3-fold in CH2Cl2; values typical for iron(II) tris(bipyridine) complexes are restored by addition of very small quantities of MeOH. Thermal properties of bpy(PEG-PLA)2 and [Fe{bpy(PEG-PLA)2}3]2+ were investigated by thermogravimetric analysis and differential scanning calorimetry, showing values typical for the polymer blocks and little effect of incorporated ligand or metal sites. Micelle-like nanoparticles of block copolymer macroligands and iron star polym...