PEG Length Research Articles

Shedding light on surface exposition of poly(ethylene glycol) and folate targeting units on nanoparticles of poly(ε-caprolactone) diblock copolymers: Beyond a paradigm

Polymeric nanoparticles (NPs) of poly(ε-caprolactone) (PCL) covered with a hydrophilic poly(ethylene glycol) (PEG) shell are usually prepared from diblock PEG-PCL copolymers through different techniques. Furthermore PEG, NPs can be decorated with targeting ligands to accumulate in specific cell lines. However, the density and conformation of PEG on the surface and its impact on the exposition of small targeting ligands has been poorly considered so far although this has a huge impact on biological behaviour. Here, we focus on PEG-PCL NPs and their folate-targeted version to encourage accumulation in cancer cells overexpressing folate receptor α. NPs were prepared with mixtures of PEG-PCL with different PEG length (short 1.0kDa, long 2.0kDa,) and a folate-functionalized PEG-PCL (PEG 1.5kDa) by the widely employed solvent displacement method. In depth characterization of NPs surface by 1H NMR, fluorescence and photon correlation spectroscopy evidenced a PEGylation extent below 7% with PEG in a mushroom conformation and the presence of folate more exposed to water pool in the case of copolymer with short PEG. NPs with short PEG adsorbed HSA forming a soft corona without aggregating. Although limited, PEGylation overall reduced NPs uptake in human macrophages. Uptake of NPs exposing folate prepared with short PEG was higher in KB cells (FR+) than in A549 (FR−), occurred via FR-receptor and involved lipid rafts-dependent endocytosis. In conclusion, the present results demonstrate that PEG length critically affects protein interaction and folate exposition with a logical impact on receptor-mediated cell uptake. Our study highlights that the too simplistic view suggesting that PEG-PCL gives PEG-coated NPs needs to be re-examined in the light of actual surface properties, which should always be considered case-by-case.

In situ crosslinking of surface-initiated ring opening metathesis polymerization of polynorbornene for improved stability

HypothesisIn situ crosslinking is expected to increase the solvent stability of coatings formed by surface-initiated ring opening metathesis polymerization (SI ROMP). Solvent-associated degradation limits the utility of SI ROMP coatings. SI ROMP coatings have a unique capacity for post-functionalization through reaction of the unsaturated site on the polymer backbone. Any post-reaction scheme which requires a liquid solvent has the potential to degrade the coating and lower the thickness of the resulting film. ExperimentsWe designed a macromolecular crosslinking group based on PEG dinorbornene. The PEG length is tailored to the expected mean chain to chain distance during surface-initiated polymerization. This crosslinking macromer is randomly copolymerized with norbornene through SI ROMP on a gold coated substrate. The solvent stability of polynorbornene coatings with and without PEG dinorbornene is quantitatively determined, and the mechanism of degradation is further supported through XPS and AFM analyses. FindingsThe addition of the 0.25mol% PEG dinorbornene significantly increases the solvent stability of the SI ROMP coatings. The crosslinker presence in the more stable films is supported with observable PEG absorbances by FTIR and an increase in contact angle hysteresis when compared to non-crosslinked coatings. The oxidation of the SI ROMP coatings is supported by the observation of carbonyl oxygen in the polynorbornene coatings. The rapid loss of the non-crosslinked SI ROMP coating corresponds to nanoscale pitting across the surface and micron-scale regions of widespread film loss. The crosslinked coatings have uniform nanoscale pitting, but the crosslinked films show no evidence of micron-scale film damage. In all, the incorporation of minimal crosslinking content is a simple strategy for improving the solvent stability of SI ROMP coatings.

Structural Characterization of PEGylated Hexaphenylalanine Nanostructures Exhibiting Green Photoluminescence Emission.

Peptides containing aromatic residues are known to exhibit spontaneous phenomena of supramolecular organization into ordered nanostructures (NSs). In this work we studied the structural behavior and optoelectronic properties of new biocompatible materials obtained by the self-assembly of a series of hexaphenylalanines (F6) modified at the N terminus by a PEG chain of different lengths. PEG12 -F6, PEG18 -F6, and PEG24 -F6 peptides were synthesized by coupling sequentially two, three, or four units of amino-carboxy-PEG6 blocks, each one containing six oxyethylene repetitions. Changes in the length and composition of the PEG chain were found to modulate the structural organization of the phenylalanine-based nanostructures. An increase in the self-aggregation tendency was observed with longer PEG chains, whereas, independently of the PEG length, the peptide NSs display cross-β-like secondary structures with an antiparallel β-strand arrangement. WAXS/GIWAXS diffraction patterns indicate a progressive decrease in fiber order along the series. All the PEG-F6 derivatives present blue photoluminescent (PL) emission at 460 nm, with the adduct with the longest PEG chain (PEG24 -F6) showing an additional green emission at 530 nm.

KGF Enhances Oral Epithelial Adhesion and Rete Peg Elongation via Integrins

Oral epithelial adhesion to the lamina propria underlies the physiologic function of the oral mucosa and contributes to resisting bacterial invasion, preventing body fluid loss, and maintaining routine chewing; thus, understanding the factors that positively influence oral epithelial adhesion is a research topic of great interest. Rete pegs contribute to oral epithelial adhesion by enlarging the contact areas, whereas integrins are the major molecules that mediate epithelial cell adhesion to the basement membrane. Keratinocyte growth factor (KGF) can promote both rete peg elongation in the skin and the expression of integrins in various cell types. Herein, we tested the effects of submucosal injection of KGF in the ventral surfaces of rat tongues on oral epithelial adhesion. The data confirmed that topical injection of KGF elevated the adhesive forces, elongated the rete pegs, and increased the abundance of integrins, KGF, and KGF receptor on the rat tongue ventral surface. However, HYD-1 (Lys-Ile-Lys-Met-Val-Ile-Ser-Trp-Lys-Gly), an integrin antagonist, inhibited the KGF-enhanced epithelial adhesion and rete peg elongation. Moreover, KGF promoted the expression of integrin subunits α6, β4, α3, and β1 in human immortalized oral epithelial cells in 2- and 3-dimensional culture systems. In vitro cell attachment assays demonstrated that HYD-1 inhibited the adhesion of human immortalized oral epithelial cells on Matrigel. Strikingly, the expression of integrins, KGF, and KGFR in human masticatory mucosae with longer rete pegs was more abundant than that in the lining mucosae with shorter rete pegs. In addition, rete peg lengths were positively correlated with the expression levels of integrins, KGF, and KGF receptor. These findings indicate that KGF strengthens oral epithelial adhesion and rete peg elongation via integrins.

Ibuprofen-loaded micelles based on star-shaped erythritol-core PLLA-PEG copolymer: effect of molecular weights of PEG

Amphiphilic star-shaped copolymers based on star-shaped poly(L-lactide) (s-PLLA) and poly(ethylene glycol) (PEG) (s-PLLA-PEG) were synthesized with variable molecular weights (Mw) of PEG, and the relationship between the PEG block molecular weight of s-PLLA-PEG copolymers and their micelle properties were investigated. The structure and Mw of s-PLLA-PEG were characterized with 1H NMR, GPC, DSC, and XRD. The ibuprofen (IBU)-loaded s-PLLA-PEG micelles were prepared by dialysis method. The effects of PEG block molecular weight on the morphology, particle size, zeta potential, drug loading content (LC), drug encapsulation efficiency (EE), and in vitro drug release behavior of prepared micelles were investigated. Results indicated that the average diameters, LC, and EE of IBU-loaded s-PLLA-PEG micelles increased with increasing the Mw of PEG in s-PLLA-PEG copolymers. The in vitro study showed that the IBU accumulative release can be depressed by increasing the Mw of the s-PLLA-PEG, and the release profiles of IBU from s-PLLA-PEG followed the Baker-Lonsdale model equation. The results suggest that structural tailoring of PEG length from s-PLLA-PEG copolymers could provide a new strategy for designing drug carriers of high efficiency.

Removal studies of Cr2O3 colloidal particles using cationic poly(l-lysine) and its block copolymers with poly(ethylene glycol)

Cr2O3 dispersions are considered to be dangerous for aqueous ecosystems and for this reason it is necessary to develop methods allowing solid particles separation.Structure of the adsorption layer formed at the solid surface determines the colloidal suspension stability. Moreover, in the case of ionic polymers the solution pH considerably affects the chains arrangement. Hence, the influence of cationic poly(l-lysine) and its copolymers adsorption on the chromium(III) oxide (Cr2O3) particles stability was investigated. Although the analyzed substances are characterized by the similar average molecular weight, they exhibit various macromolecular structures resulting from the different PEG and polyamino acid length ratios. The sample's stability was examined by the use of the turbidimetric method enabling the Turbiscan Stability Index (TSI) parameter calculation.As one can see, solid suspensions without the tested polymers are relatively unstable. At pH 4, introduction of the cationic macromolecules causes the increase in the sample stability. This can be explained by the electrostatic repulsion between the totally ionized polymeric chains adsorbed on the adjacent Cr2O3 particles. At pHpzc, changes in the TSI values are related to the different polymer chain arrangements.

Lightning rod resonance of a plasmonic near-field transducer.

We demonstrate the lightning-rod resonance of a lollipop near-field transducer integrated in magnetic writer for heat-assisted magnetic recording by collecting the two-photon excited photoluminescence (TPL) signal when excited by a pulsed femto-second fiber laser tuned to the desired mode resonance. The lollipop transducer consists of a round disk and a protruding peg to take advantage of the lightning-rod effect. It is found that the TPL signal is extremely sensitive to the peg length where even a 3-5 nm deviation from the optimal peg length halves the TPL signal. This method conveniently quantifies the optical performance of an NFT device in situ as a function of geometry with a resolution of better than the light wavelength (λ) divided by 200.

A Trivalent Enzymatic System for Uricolytic Therapy of HPRT Deficiency and Lesch-Nyhan Disease

PurposeBecause of the evolutionary loss of the uricolytic pathway, humans accumulate poorly soluble urate as the final product of purine catabolism. Restoration of uricolysis through enzyme therapy is a promising treatment for severe hyperuricemia caused by deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT). To this end, we studied the effect of PEG conjugation on the activity and stability of the enzymatic complement required for conversion of urate into the more soluble (S)-allantoin.MethodsWe produced in recombinant form three zebrafish enzymes required in the uricolytic pathway. We carried out a systematic study of the effect of PEGylation on the function and stability of the three enzymes by varying PEG length, chemistry and degree of conjugation. We assayed in vitro the uricolytic activity of the PEGylated enzymatic triad.ResultsWe defined conditions that allow PEGylated enzymes to retain native-like enzymatic activity even after lyophilization or prolonged storage. A combination of the three enzymes in an appropriate ratio allowed efficient conversion of urate to (S)-allantoin with no accumulation of intermediate metabolites.ConclusionsPharmaceutical restoration of the uricolytic pathway is a viable approach for the treatment of severe hyperuricemia.

Structural and Rheological Properties of Temperature-Responsive Amphiphilic Triblock Copolymers in Aqueous Media.

Thermoresponsive amphiphilic biodegradable block copolymers of the type poly(ε-caprolactone-co-lactide)-poly(ethylene glycol)-poly(ε-caprolactone-co-lactide) (PCLA-PEGm-PCLA) have great potential for various biomedical applications. In the present study, we have surveyed the effects of PEG spacer length (m = 1000 and 1500), temperature, and polymer concentration on the self-assembling process to form supramolecular structures in aqueous solutions of the PCLA-PEGm-PCLA copolymer. This copolymer has a lower critical solution temperature, and the cloud point depends on both concentration and PEG length. Thermoreversible hydrogels are formed in the semidilute regime; the gel windows in the phase diagrams can be tuned by the concentration and length of the PEG spacer. The rheological properties of both dilute and semidilute samples were characterized; especially the sol-to-gel transition was examined. Small-angle neutron scattering (SANS) experiments reveal fundamental structural differences between the two copolymers for both dilute and semidilute samples. The intensity profiles for the copolymer with the long PEG spacer could be described by a spherical core-shell model over a broad temperature domain, whereas the copolymer with the short hydrophilic spacer forms rod-like species over an extended temperature range. This finding is supported by cryo-TEM images. At temperatures approaching macroscopic phase separation, both copolymers seem to assume extended rod-like structures.

Optimization of a PEGylated Glucuronide-Monomethylauristatin E Linker for Antibody–Drug Conjugates

The emergence of antibody-drug conjugates (ADC), such as brentuximab vedotin and ado-trastuzumab emtansine, has led to increased efforts to identify new payloads and develop improved drug-linker technologies. Most antibody payloads impart significant hydrophobicity to the ADC, resulting in accelerated plasma clearance and suboptimal in vivo activity, particularly for conjugates with high drug-to-antibody ratios (DAR). We recently reported on the incorporation of a discrete PEG24 polymer as a side chain in a β-glucuronidase-cleavable monomethylauristatin E (MMAE) linker to provide homogeneous DAR 8 conjugates with decreased plasma clearance and increased antitumor activity in xenograft models relative to a non-PEGylated control. In this work, we optimized the drug-linker by minimizing the size of the PEG side chain and incorporating a self-stabilizing maleimide to prevent payload de-conjugation in vivo Multiple PEG-glucuronide-MMAE linkers were prepared with PEG size up to 24 ethylene oxide units, and homogeneous DAR 8 ADCs were evaluated. A clear relationship was observed between PEG length and conjugate pharmacology when tested in vivo Longer PEG chains resulted in slower clearance, with a threshold length of PEG8 beyond which clearance was not impacted. Conjugates bearing PEG of sufficient length to minimize plasma clearance provided a wider therapeutic window relative to faster clearing conjugates bearing shorter PEGs. A lead PEGylated glucuronide-MMAE linker was identified incorporating a self-stabilizing maleimide and a PEG12 side chain emerged from these efforts, enabling highly potent, homogeneous DAR 8 conjugates and is under consideration for future ADC programs. Mol Cancer Ther; 16(1); 116-23. ©2016 AACR.

Correction: PEGylated gold nanoparticles: polymer quantification as a function of PEG lengths and nanoparticle dimensions

Correction for ‘PEGylated gold nanoparticles: polymer quantification as a function of PEG lengths and nanoparticle dimensions’ by Kamil Rahme et al., RSC Adv., 2013, 3, 6085–6094.

Effects of the PEG length of polycarboxylate-based terpolymers on their dispersion properties

Polycarboxylate-based terpolymers with different PEG length, PAE-Na, were synthesized by free radical emulsion polymerization. The monomers are Poly(ethylene glycol) monomethyl ether monomethacrylate (PMEM, Mn=950g/mol, 500g/mol and 300g/mol), 2-ethylhexyl acrylate (2-EHA) and acrylic acid (AA), respectively. The structures of terpolymers were characterized by 1H NMR and FT-IR. This particular molecular structure of terpolymers guarantees its good dispersibility. Here, PAE-Na terpolymers were used as dispersant and CaCO3 as solid suspension to calculate the dispersion amounts (DAs) by means of titration method. PAE-Na terpolymers with different PEG length show great differences in DAs. Furthermore, the particle size distribution (PSD) and transmission electron microscopy (TEM) were carried out to evaluate the particle size of CaCO3 suspensions. The experiment results show that the dispersibility of terpolymers has an increasing trend while increasing the PEG side chain length. Based on the theory of Flatt and Scaling law, the molecule size of terpolymers with different length of PEG side chain was calculated. The Flory energy as a function H was calculated when two particles approach. Finally, the anti-redepositing power of 3# terpolymer was investigated. The result shows that 3# terpolymer has strong anti-redepositing power. This study may help elucidate the mechanism of dispersion and develop structure-property relationships which could provide theoretical guidance in the design of molecular structure in the practical application.

Parametric analysis of glenoid implant design and fixation type.

Common post-operative problems in shoulder arthroplasty such as glenoid loosening and joint instability may be reduced by improvements in glenoid design, shape, material choice, and fixation method. A framework for parametric analysis of different implant fixation configurations was developed in order to efficiently sift through potential glenoid component designs. We investigated the influence of design factors such as fixation type, component thickness, and peg position, number, diameter, and length in a multi-factorial design investigation. The proposed method allowed for simultaneous comparison of the mechanical performance of 344 different parametric variations of 10 different reference geometries with either large central fixation features or small peripheral pegs, undergoing four different worst-case scenario loading conditions, and averaging 64.7 s per model. The impact of design parameters were assessed for different factors responsible for post-operative problems in shoulder arthroplasty, such as bone volume preservation, stresses in the implant, central displacement or fixation stability, and the worst performing geometries all relied on conventional central fixation. Of the remaining geometries, four peripheral fixation configurations produced von Mises stresses comfortably below the material's yield strength. We show that the developed method allows for simple, direct, rapid, and repeatable comparison of different design features, material choices, or fixation methods by analyzing how they influence the bone-implant mechanical environment. The proposed method can provide valuable insight in implant design optimization by screening through multiple potential design modifications at an early design evaluation stage and highlighting the best performing combinations according to the failure mechanism to mitigate. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:775-784, 2017.

Nano-supramolecular complex synthesis: Switch on/off enhanced fluorescence control and molecular release using a simple chemistry reaction

A nanosensor based on β-cyclodextrin (βCD) macrocycles linked to gold nanoparticles for rhodamine B (RhB) sensing was developed applying the metal-enhanced fluorescence effect (MEF). Hence, we have developed many ways to control the distance of supramolecular systems to nanoparticle surface with different bioconjugation strategies in order to optimize signal detection. Different PEG spacer arm lengths were used to cover the nanoparticle surface with molecular spacers. This type of molecular shell is biocompatible, enabling to switch on/off the MEF effect using a dithiane linker by a simple reduction reaction. In the presence of the nanosensor obtained, an increase was observed in RhB fluorescence emission depending on molecular length, that is a characteristic effect of MEF. The major increase measured was 60% compared with RhB emission in buffer at 1nM level, for a spacer length of 3.58nm and an 80% increase as compared with that in the presence of βCD. These differences are ascribed to the fact that, in the presence of macrocycle, we can observe a well-known quenching effect that is overcome by the presence of the metallic core. Even at shorter spacer distances, with PEG lengths of 1.2 and 2.17nm, increases of 25 and 47% respectively allow the analyte detection by the RhB complexation with βCD. The optimal MEF enhancement was measured with the maximal emission signal stabilized after 50min due to plasmonic effects based on inter nanoparticle interactions. Moreover, the emission increase, in the presence of the metallic core, was accompanied with a diminution in the fluorescence lifetime's decay value averages, characteristic of MEF. This fact shows that the excited state is protected from the non-radiative emission decays enhancing the analytical signal.

Effect of type of poly(ethylene glycol) (PEG) based amphiphilic copolymer on antifouling properties of copolymer/poly(vinylidene fluoride) (PVDF) blend membranes

The antifouling properties of poly(vinylidene fluoride) (PVDF) membranes were investigated by blending several types of synthesized amphiphilic poly(poly(ethylene glycol) methyl ether methacrylate- methyl methacrylate) [P(PEGMA- MMA)] copolymers with different initial PEGMA/MMA monomer ratios and PEG side chain lengths. Many types of membranes were prepared using different copolymer/PVDF blend ratios via nonsolvent induced phase separation. The membranes with similar pure water permeabilities and surface pore sizes were prepared by controlling the dope solution composition. Thus, the bovine serum albumin antifouling properties could be assessed under similar hydrodynamic filtration conditions. The membrane hydrophilicity, surface PEGMA coverage, and antifouling properties of the prepared membranes increased with increasing copolymer/PVDF ratio and PEGMA/MMA monomer ratio of the copolymers and PEG length of the copolymer. A molecular dynamics simulation was performed to assess the surface chemical composition, and the results were compared with those of X-ray photoelectron spectroscopy. The antifouling properties depended more strongly on the membrane surface hydrophilicity when the copolymer chemical structures, that is, the PEGMA/MMA monomer ratio and PEG side chain length, were changed, rather than when the copolymer/PVDF blend ratio was changed.

MMP2-Sensitive PEG-Lipid Copolymers: A New Type of Tumor-Targeted P-Glycoprotein Inhibitor.

Low tumor targetability and multidrug resistance (MDR) are two major impediments to the success of cancer treatments. Nanomaterials which possess high tumor targetability and the ability to reverse the MDR are rare. This report describes a new type of self-assembling polyethylene glycol-phosphoethanolamine-based copolymers (PEG-pp-PE) which showed both the matrix metalloproteinase 2 (MMP2)-sensitive tumor-targeted drug delivery and ability to inhibit the P-glycoprotein (P-gp)-mediated drug efflux. In this study, we synthesized a series of the homologous analogues of PEG-pp-PE copolymers and investigated the influence of their structures, including PEG lengths and peptide linkers, on the drug efflux, and identified the underlying mechanisms. We found that the whole structure (PEG-peptide-lipid) rather than any parts of the copolymers was key for the P-gp inhibition and a delicate balance between the hydrophilic and lipophilic segments of the PEG-pp-PE copolymers was needed for better modulating the P-gp-mediated drug efflux. The best copolymer, PEG2k-pp-PE, showed even higher P-gp inhibition effect than the d-α-tocopherol polyethylene glycol 1000 succinate (TPGS1k). We also found that the P-gp inhibition capability of PEG-pp-PE copolymers was highly associated with the P-gp down-regulation, the increase in the plasma membrane fluidity, and the inhibition of the P-gp ATPase activity. Besides, the excellent physicochemical properties, high drug loading, MMP2-dependent drug release, and improved drug efficacy in the MDR cancer cells suggested that the PEG-pp-PE copolymers might have great potential for building tumor-targeted drug delivery systems for treating drug-resistant cancers.

Controlling Interlamellar Spacing in Periodically Grafted Amphiphilic Copolymers

We have examined a series of periodically grafted amphiphilic copolymers (PGACs) wherein pendant MPEG segments of varying lengths (TREG, 350, 550, and 750) were grafted at periodic intervals along a long crystallizable alkylene (C-20) backbone. The immiscibility of the alkylene and PEG segments, and the strong propensity of the alkylene segments to crystallize, drive these PGACs to self-segregate by folding in a zigzag fashion and subsequently organize into a lamellar morphology, which was evident from DSC, SAXS, WAXS, and AFM studies; the interlamellar spacing was seen to increase linearly with MPEG length. Co-grafted PGACs, prepared by grafting a mixture of two different MPEGs (MPEG 350 and MPEG 750), also exhibited a lamellar morphology; interestingly, the interlamellar spacing was seen to depend only on the total PEG content, while the presence of a mixture of PEG lengths exerted little influence. However, a mixture of two homo-PGACs bearing either pendant MPEG350 or MPEG750 segments underwent macroph...

Microparticles on the Basis of Segmented Polyurethanes for Drug Respiratory Administration

Microparticles based on segmented polyurethane were synthesized by polycondensation of a series of diols having various molecular weight with tolyene-2,4-diisocyanate in water-in-oil emulsion. The resulting spherical microparticles were 6-10 μm in diameter following the Gauss distribution. The size of microcapsules at maximum distribution band increases with growing PEG length. It was observed that with higher length of PEG wall surfaces of capsules become more stable mechanically, however a capsule itself is no more brittle and rough. Some aggregation also occurs for microparticles based on PEG 4200. Since respiratory way of drug administration considers size of particles within 1-10 μm as the most applicable, the resulting PU microparticles could be an ideal candidate as domain for respirable antiTB drug administration.

Effect of Surface Functionalization on the Cellular Uptake and Toxicity of Nanozeolite A.

Extensive use of zeolite nanoparticles in many areas, including medicine, has led to the concern about an impact and possible risk of their use for human health and the environment.In our studies, we investigated an uptake, retention, and cytotoxicity of nanozeolite A (BaA) functionalized with aminopropyl or poly(ethylene glycol) (PEG) of different chain lengths using human cervical carcinoma cell line. For internalization studies, nanozeolite was labeled with 133Ba radionuclide.The results show that in the case of PEG modification, toxicity and uptake depend on the PEG chain length. The highest toxicity has been observed for nanozeolites coated with short-length chain (Ba-silane-PEGm(MW350). Also, amine-modified nanozeolites exhibited high toxicity, while nanozeolites coated with long PEG molecules, BaA-silane-PEGm(MW1000), and BaA-silane-PEGm(MW2000), as well as unmodified nanozeolite, seem to be nontoxic.In conclusion, this study shows that uptake, retention, and toxicity of nanozeolites coated with various length PEG molecules groups depend on the molecular weight of PEG.Electronic supplementary materialThe online version of this article (doi:10.1186/s11671-016-1334-8) contains supplementary material, which is available to authorized users.

PCL-PEG graft copolymers with tunable amphiphilicity as efficient drug delivery systems.

The development of flexible drug delivery systems that can be tuned as a function of the drug to be delivered and of the target disease is crucial in modern medicine. For this aim, novel amphiphilic poly(ε-caprolactone)-g-poly(ethylene glycol) (PCL-g-PEG) copolymers with well-controlled design were synthesized by thiol-yne photochemistry. The grafting density and the copolymer amphiphilicity were easily controlled via the reaction parameters: concentration, reaction time, PEG length and the molar ratio between PCL and PEG or the photoinitiator in the reaction mixture. The self-assembling behavior of the copolymers was studied and a correlation between the composition of PCL-g-PEG and the nanoaggregate diameter sizes (28 to 73 nm) and critical aggregation concentrations (1.1 to 4.3 mg L-1) was found. The influence of copolymer amphiphilicity on the drug loading was evaluated with various drugs including anticancer drugs (paclitaxel, ABT-199), drugs to overcome multidrug resistance in cancer cells (curcumin, elacridar), an anti-inflammatory drug (dexamethasone) and an antibacterial drug (clofazimine). Finally, the influence of amphiphilicity on curcumin release and toxicity towards MCF-7 cancer cell lines was studied. The impact of the grafting density, PEG length and the overall EG/CL ratio is discussed in detail. Curcumin loaded PCL-g-PEG with lower EG/CL ratios and shorter PEG chains showed higher toxicity compared to their more hydrophilic counterparts.