Statistical Copolymers Research Articles

Facile Synthesis of Catechol-Containing Polyacrylamide Copolymers: Synergistic Effects of Amine, Amide and Catechol Residues in Mussel-Inspired Adhesives.

The straightforward synthesis of polyamide-derived statistical copolymers with catechol, amine, amide and hydroxy residues via free radical polymerization is presented. In particular, catechol, amine and amide residues are present in natural mussel foot proteins, enabling strong underwater adhesion due to synergistic effects where cationic residues displace hydration and ion layers, followed by strong short-rang hydrogen bonding between the catechol or primary amides and SiO2 surfaces. The present study is aimed at investigating whether such synergistic effects also exist for statistical copolymer systems that lack the sequence-defined positioning of functional groups in mussel foot proteins. A series of copolymers is established and the adsorption in saline solutions on SiO2 is determined by quartz crystal microbalance measurements and ellipsometry. These studies confirm a synergy between cationic amine groups with catechol units and primary amide groups via an increased adsorptivity and increased polymer layer thicknesses. Therefore, the free radical polymerization of catechol, amine and amide monomers as shown here may lead to simplified mussel-inspired adhesives that can be prepared with the readily scalable methods required for large-scale applications.

Real-time 31P NMR reveals different gradient strengths in polyphosphoester copolymers as potential MRI-traceable nanomaterials

Polyphosphoesters (PPEs) are used in tissue engineering and drug delivery, as polyelectrolytes, and flame-retardants. Mostly polyphosphates have been investigated but copolymers involving different PPE subclasses have been rarely explored and the reactivity ratios of different cyclic phospholanes have not been reported. We synthesized binary and ternary PPE copolymers using cyclic comonomers, including side-chain phosphonates, phosphates, thiophosphate, and in-chain phosphonates, through organocatalyzed ring-opening copolymerization. Reactivity ratios were determined for all cases, including ternary PPE copolymers, using different nonterminal models. By combining different comonomers and organocatalysts, we created gradient copolymers with adjustable amphiphilicity and microstructure. Reactivity ratios ranging from 0.02 to 44 were observed for different comonomer sets. Statistical ring-opening copolymerization enabled the synthesis of amphiphilic gradient copolymers in a one-pot procedure, exhibiting tunable interfacial and magnetic resonance imaging (MRI) properties. These copolymers self-assembled in aqueous solutions, 31 P MRI imaging confirmed their potential as MRI-traceable nanostructures. This systematic study expands the possibilities of PPE-copolymers for drug delivery and theranostics.

Homology Violation in a Series of Amphiphilic Comb-Like Statistical Copolymers of N-Methyl-N-vinylacetamide and N-Methyl-N-vinylamine with Moderate Density of Grafting of Side Dodecyl Groups

A series of water-soluble comb-like copolymers of N-methyl-N-vinylacetamide and N-methyl-N-vinylamine (MVAA‒со‒MVA) bearing hydrophobic dodecyl side groups С12Н25 has been investigated by means of molecular hydrodynamics (viscometry, translational diffusion, and analytical ultracentrifugation) in dilute solutions in 0.1 M NaCl, under conditions of suppression of the polyelectrolyte effects. The issues of homology of these amphiphilic copolymers have been considered. The viscometry data plotted as lnηr as function of c[η] have allowed to distinguish between macromolecules of the copolymers according to their hydrophobicity. Positive values of the second derivative B2 determined from the initial parts of these curves have served as a measure of hydrophobicity of the amphiphilic copolymers. The noticeable differences in the B2 values for different copolymers have shown that they do not form true homologous series. For the quasi-homologous series of the MVAA–со–MVAC12H25·HI copolymers with close values of B2, the Kuhn–Mark–Houwink–Sakurada relationships have been obtained and the equilibrium rigidity of the chains has been assessed using the modified Gray–Bloomfield–Hearst equation.

Copolymer Brush Particle Hybrid Materials with "Recall-and-Repair" Capability.

The effect of sequence structure on the self-healing and shape-memory properties of copolymer-tethered brush particle films was investigated and compared to linear copolymer analogs. Poly(n-butyl acrylate-co-methyl methacrylate), P(BA-co-MMA), and linear and brush analogs with controlled gradient and statistical sequence were synthesized by atom transfer radical polymerization (ATRP). The effect of sequence on self-healing in BA/MMA copolymer brush particle hybrids followed similar trends as for linear analogs. Most rapid restoration of mechanical properties was found for statistical copolymer sequence; an increase of the high Tg (MMA) component provided a path to raise the material's modulus while retaining self-heal ability. Creep testing revealed profound differences between linear and brush systems. While linear copolymers featured substantial viscous deformation when exposed to constant stress in the linear regime, brush analogs displayed minimal permanent deformation and featured shape restoration. The reduction of flow was interpreted to be a consequence of slow cooperative relaxation due to the complex microstructure of brush particle hybrids in which long-range motions are constrained through entanglements and slow-diffusing particle cores. The rubbery-like response imparts BA/MMA copolymer brush material systems concurrent "shape-memory" and "self-heal" capability. This ability to "recall-and-repair" could find application in the design of functional hybrid materials, for example, for soft robotics.

Wear resistance by copolymers with controlled structure under boundary lubrication conditions

AbstractLubricants are of paramount importance in protecting metallic contact surfaces and reducing friction. The viscosity of lubricating oil can be engineered by introducing long linear polymers, such as poly(lauryl methacrylate) (PLMA). In particular, the formation of adsorption films by using polymers with hydroxy or amino side groups has attracted much attention in recent years. In this study, copolymers with controlled structure were synthesised by SARA ATRP, which can be used in large scale production. A comparison of friction and wear under boundary lubrication was conducted using both statistical and block copolymers with low Ð. Friction test results using a reciprocating sliding machine (SRV) showed that the block copolymers were less likely to desorb from the metal surface than the statistical copolymers. In addition, the wear evaluation after the SRV test showed that the block copolymer had less wear and less wear debris.

CO2-switchable thermoresponsiveness of poly(N,N-(diethylamino)ethyl acrylamide)-based homo- and copolymers in water

The properties of thermo-sensitive polymers can be easily and reversibly switched using addition/removal of carbon dioxide (CO2) as an innovative and ecological trigger. N,N-(diethylamino)ethyl acrylamide (DEAEAM) was copolymerized with N-isopropylacrylamide (NIPAM) by Reversible Addition-Fragmentation chain Transfer (RAFT) polymerization to obtain copolymers with various compositions and architectures. The properties (solubility, aggregation behavior…) of these polymers in aqueous solution in the presence of CO2 was studied via scattering, microscopy and turbidimetry measurements. The copolymerization of DEAEAM monomer with NIPAM enables to produce either statistical or diblock copolymers and to tune the cloud point temperature of obtained copolymers either by changing the composition or the architecture (statistical, block) or by CO2 addition/removal. Whereas, for a given composition, statistical copolymer does not display thermoresponsive behavior, block copolymers present a thermoresponsiveness which depends on the protonation degree of tertiary amine functions. Additionally, CO2 can be used to reversibly modulate the properties of these materials in aqueous media.

Molecular Architecture of Multiblock Copolymers Synthesized by the Chain Shuttling Technology

AbstractRecent advances in the characterization of ethylene/1‐octene‐based statistical multiblock copolymers (MBCs) synthesized via chain shuttling copolymerization are illustrated. The Perspective focuses on the peculiarity of MBC systems that consists in the nonuniform chain architecture of these intriguing systems due to compositional heterogeneity occurring at inter‐ and intra‐chain level. In the first part, the effect of dispersity on the phase behavior and properties of MBCs and block copolymers in general is discussed along with the consequences of crystallization of one of the blocks on microphase separation, domain spacing, and morphology. In the second part, the main results achieved in the elucidation of details of the chain microstructure in terms of average length of the blocks and block length distribution are presented. It is shown that solvent and thermal fractionation techniques, coupled with other techniques such as transmission electron microscopy (TEM) and small angle X‐ray scattering (SAXS) represent powerful tools to elucidate the inter‐ and intra‐chain heterogeneous composition of the MBCs. Guidelines on how to establish structure/properties relationships for such polydisperse systems are also provided.

Synthetic Star Nanoengineered Antimicrobial Polymers as Antibiofilm Agents: Bacterial Membrane Disruption and Cell Aggregation.

Antimicrobial resistance has become a worldwide issue, with multiresistant bacterial strains emerging at an alarming rate. Multivalent antimicrobial polymer architectures such as bottle brush or star polymers have shown great potential, as they could lead to enhanced binding and interaction with the bacterial cell membrane. In this study, a library of amphiphilic star copolymers and their linear copolymer equivalents, based on acrylamide monomers, were synthesized via RAFT polymerization. Their monomer distribution and molecular weight were varied. Subsequently, their antimicrobial activity toward a Gram-negative bacterium (Pseudomonas aeruginosa PA14) and a Gram-positive bacterium (Staphylococcus aureus USA300) and their hemocompatibility were investigated. The statistical star copolymer, S-SP25, showed an improved antimicrobial activity compared to its linear equivalent againstP. aeruginosaPA14. The star architecture enhanced its antimicrobial activity, causing bacterial cell aggregation, as revealed via electron microscopy. However, it also induced increased red blood cell aggregation compared to its linear equivalents. Changing/shifting the position of the cationic block to the core of the structure prevents the cell aggregation effect while maintaining a potent antimicrobial activity for the smallest star copolymer. Finally, this compound showed antibiofilm properties against a robust in vitro biofilm model.

Toughening of Bio-Based PA6.19 by Copolymerization with PA 6.6 - Synthesis and Production of Melt-Spun Monofilaments and Knitted Fabrics.

This work reports on the synthesis of statistical copolymers of bio-based PA6.19 and PA6.6 together with the production of melt-spun monofilaments for the production of sustainable textile fibers. The plant oil-based 1.19-nonadecanedioic acid is synthesized from bio-derived oleic acid via isomerizing methoxycarbonylation. The homopolymer PA6.19 with a carbon-based bio-content of 72% showsa good elongation at break of 166%, but lower tensile strength than commercial PA6 (43MPa versus 82MPa). Addition of adipic acid to form statistical PA 6.6/6.19 copolymers improves toughness while maintaining the high elongation at break. Two PA6.6/6.19 copolymers with a carbon-based bio-content of 26% and 33% are successfully synthesized and exhibited comparable toughness (94 ± 6MPa and 92 ± 2MPa) to the commercial PA6 (92 ± 15MPa). The bio-based copolymers also exhibit a much lower water uptake than PA 6 and PA 6.6, resulting in a higher dimensional stability. Melt spinning of the oleic acid-based polyamides is successfully carried out to produce monofilaments with sufficient properties for further processing in a knitting process, demonstrating the capabilities of the bio-based PA6.6/6.19 copolymers for use in the textile industry.

Statistical Copolymers Comprising Bio‐Based Aromatic Methacrylate Segments and Their Influence on the Glass Transition Temperature

Front Cover: In article 2300031 by Veronika Strehmel and co-workers, copolymers made from 4-(4-methacryloyloxyphenyl)butan-2-one originating from birch bark and an aliphatic methacrylate, e.g., n-butyl methacrylate, show an increase in the glass transition temperature with increasing content on the aromatic segments that may be interesting for application in coatings.

Thermogels based on biocompatible OEGMA-MEGMA diblock copolymers

A series of biocompatible thermoresponsive copolymers were successfully synthesised via group transfer polymerisation (GTP) from methoxy ethylene glycol methacrylate (MEGMA) and methoxy oligo (ethylene glycol) methacrylate (OEGMA, Mn = 300 g mol -1). Statistical and diblock copolymers with molar mass around 8100 g mol−1 and various compositions were investigated. Specifically, the content in OEGMA and MEGMA was varied from 80 to 20, 70–30, 60–40, to 50–50 w/w%. The thermoresponsive and self-assembly behaviour of the copolymers was investigated throughvisual tests, rheology, dynamic light scattering (DLS) and transmission electron microscopy (TEM). Interestingly, the diblock copolymers with higher MEGMA content were able to form gels at relatively low concentrations (as low as 5% w/w) when increasing the temperature, something that is reported for the first time for linear ethylene glycol based copolymers. A transition of spherical micelle to worm-like micelle was observed in these diblock copolymers that promotes gelation. Furthermore, these in-house synthesised polymers were mixed with Pluronic® F127. It was found that the gelation area of Pluronic® F127 was broadened by the addition of the synthesised copolymers with one formulation, specifically a combination of 12.5% w/w Pluronic® F127 and 12.5% w/w of a statistical OEGMA-co-MEGMA, forming a stable gel from 34 °C to 48 °C that is a desirable temperature range for biological applications. Finally, cell viability experiments were performed for the three most promising diblock copolymers and they were confirmed to be non-toxic.

Synthesis and Micellization Behavior of Amphiphilic Block Copolymers of Poly(N-vinyl Pyrrolidone) and Poly(Benzyl Methacrylate): Block versus Statistical Copolymers.

Block copolymers of N-vinyl pyrrolidone (NVP) and benzyl methacrylate (BzMA), PNVP-b-PBzMA, were prepared by RAFT polymerization techniques and sequential addition of monomers. The copolymers were characterized by Size Exclusion Chromatography (SEC) and NMR spectroscopy. Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA) and Differential Thermogravimetry (DTG) were employed to study the thermal properties of these copolymers. The micellization behavior in THF, which is a selective solvent for the PBzMA blocks, was examined. For comparison the self-assembly properties of the corresponding statistical copolymers, PNVP-stat-PBzMA, were studied. In addition, the association behavior in aqueous solutions was analyzed for the block copolymers, PNVP-b-PBzMA. In this case, the solvent is selective for the PNVP blocks. Dilute solution viscometry, static (SLS) and dynamic light scattering (DLS) were employed as the tools to investigate the micellar assemblies. The efficient encapsulation of the hydrophobic curcumin within the micellar core of the supramolecular structures in aqueous solutions was demonstrated by UV-Vis spectroscopy and DLS measurements.

Exploring the influence of rigid carbocycles on terpenoid copolymer properties

AbstractSynthesizing soft polymers with uncommon architectural elements is critical for enhancing our understanding of fundamental structure–property relationships in macromolecules. Terpenoid materials are interesting candidates for addressing this grand challenge, as their constituent monomers can exhibit a diverse array of structural and functional groups. Moreover, these biologically‐derived materials can potentially expand the sphere of knowledge surrounding trends in related petrochemically‐derived polymers. For example, vinyl‐addition copolymers of norbornene and acyclic olefins can exhibit predictable properties (e.g., linear changes in Tg as a function of composition). Due to synthetic limitations, however, it is not well understood if other rigid carbocycles engender similar behavior in a range of copolymers. As numerous terpene scaffolds display rigid motifs (such as pinane systems), terpenoid polymers are uniquely positioned to address this deficiency. Here, we report the synthesis and characterization of terpenoid copolymers (both statistical and block) with systematically tailored compositions of pinene‐based comonomers. We found that the pinane core (which is a constitutional isomer of norbornene) appears to promote ideal behavior with regard to bulk thermal properties of statistical copolymers, which mirrors the behavior of norbornene‐based systems. We also found that block copolymers exhibited thermomechanical properties that were highly tunable (and apparently correlated to carbocycle composition).

Interface Manipulations Using Cross-Linked Underlayers and Surface-Active Diblock Copolymers to Extend Morphological Diversity in High-χ Diblock Copolymer Thin Films

Top and bottom interfaces of high-χ cylinder-forming polystyrene-block-maltoheptaose (PS-b-MH) diblock copolymer (BCP) thin films are manipulated using cross-linked copolymer underlayers and a fluorinated phase-preferential surface-active polymer (SAP) additive to direct the self-assembly (both morphology and orientation) of BCP microdomains into sub-10 nm patterns. A series of four photo-cross-linkable statistical copolymers with various contents of styrene, a 4-vinylbenzyl azide cross-linker, and a carbohydrate-based acrylamide are processed into 15 nm-thick cross-linked passivation layers on silicon substrates. A partially fluorinated analogue of the PS-b-MH phase-preferential SAP additive is designed to tune the surface energy of the top interface. The self-assembly of PS-b-MH thin films on top of different cross-linked underlayers and including 0-20 wt % of SAP additive is investigated by atomic force microscopy and synchrotron grazing incidence small-angle X-ray scattering analysis. The precise manipulation of the interfaces of ca. 30 nm thick PS-b-MH films not only allows the control of the in-plane/out-of-plane orientation of hexagonally packed (HEX) cylinders but also promotes epitaxial order-order transitions from HEX cylinders to either face-centered orthorhombic or body-centered cubic spheres without modifying the volume fraction of both blocks. This general approach paves the way for the controlled self-assembly of other high-χ BCP systems.

Statistical Copolymers Comprising Bio‐Based Aromatic Methacrylate Segments and Their Influence on the Glass Transition Temperature

AbstractSynthesis of statistical copolymers is described from bio‐based 4‐(4‐methacryloyloxyphenyl)butan‐2‐one (1) with an aliphatic methacrylate, such asn‐butyl methacrylate (2),N,N‐(dimethylamino)ethyl methacrylate (3), and lauryl methacrylate (4), using mostly dimethyl sulfoxide as solvent in the free radical polymerization. Though4 is insoluble in dimethyl sulfoxide, diethyl carbonate is the preferred solvent for the copolymerization using this monomer although both yield and molecular weight are lower even for poly(4‐(4‐methacryloyloxyphenyl)butan‐2‐one) than using dimethyl sulfoxide as solvent.1H NMR spectroscopic analysis gives information about the content on the monomer segments in all copolymers. Furthermore, elementary analysis additionally supports the results obtained for the copolymers made from1 and3. As shown by the copolymerization diagrams and the copolymerization parameters, the copolymerization of1with2is a nearly ideal copolymerization using short polymerization time (20 min). Extending the polymerization time results in slight deviation from an ideal copolymerization. Furthermore, the glass transition temperature of the copolymers determined by DSC and calculated using both the Fox equation and the Gibbs‐DiMarzio equation show the strong influence of the copolymer composition. As expected, the glass transition temperature increases with increasing content on aromatic segments in the copolymer that may be interesting for application in coatings and adhesives, respectively.

All-Polyhydroxyalkanoate Triblock Copolymers via a Stereoselective-Chemocatalytic Route

Biodegradable polyhydroxyalkanoate (PHA) homopolymers and statistical copolymers are ubiquitous in microbially produced PHAs, but the step-growth polycondensation mechanism the biosynthesis operates on presents a challenge to access well-defined block copolymers (BCPs), especially higher-order tri-BCP PHAs. Here we report a stereoselective-chemocatalytic route to produce discrete hard-soft-hard ABA all-PHA tri-BCPs based on the living chain-growth ring-opening polymerization of racemic (rac) 8-membered diolides (rac-8DLR; R denotes the two substituents on the ring). Depending on the composition of the soft B block, originated from rac-8DLR (R = Et, nBu), and its ratio to the semicrystalline, high-melting hard A block, derived from rac-8DLMe, the resulting all-PHA tri-BCPs with high molar mass (Mn up to 238 kg mol-1) and low dispersity (Đ = 1.07) exhibit tunable mechanical properties characteristic of a strong and tough thermoplastic, elastomer, or a semicrystalline thermoplastic elastomer.

Statistical Copolymers of N-Vinylpyrrolidone and 2-Chloroethyl Vinyl Ether via Radical RAFT Polymerization: Monomer Reactivity Ratios, Thermal Properties, and Kinetics of Thermal Decomposition of the Statistical Copolymers.

The radical statistical copolymerization of N-vinyl pyrrolidone (NVP) and 2-chloroethyl vinyl ether (CEVE) was conducted using the Reversible Addition-Fragmentation chain Transfer (RAFT) polymerization technique, employing [(O-ethylxanthyl)methyl]benzene (CTA-1) and O-ethyl S-(phthalimidylmethyl) xanthate (CTA-2) as the Chain Transfer Agents (CTAs), leading to P(NVP-stat-CEVE) products. After optimizing copolymerization conditions, monomer reactivity ratios were estimated using various linear graphical methods, as well as the COPOINT program, which was applied in the framework of the terminal model. Structural parameters of the copolymers were obtained by calculating the dyad sequence fractions and the monomers' mean sequence lengths. Thermal properties of the copolymers were studied by Differential Scanning Calorimetry (DSC) and kinetics of their thermal degradation by Thermogravimetric Analysis (TGA) and Differential Thermogravimetry (DTG), applying the isoconversional methodologies of Ozawa-Flynn-Wall (OFW) and Kissinger-Akahira-Sunose (KAS).

The Energy Characteristics of the Surface of Statistical Copolymers.

The results of systematic studies on the surface energy γ and its polar γP and dispersion γD components of statistical copolymers of styrene and butadiene, acrylonitrile and butadiene, and butyl acrylate and vinyl acetate, with regard to their thermal prehistory, are generalized. Along with copolymers, the surfaces of their composing homopolymers were examined. We obtained the energy characteristics of the adhesive surfaces of copolymers that contacted with air, high-energy aluminium Al (γ = 160 mJ/m2), and the low-energy substrate surface of polytetrafluoroethylene F4 (PTFE) (γ = 18 mJ/m2). The surfaces of copolymers in contact with air, aluminium, and PTFE were investigated for the first time. It was found that the surface energy of these copolymers tended to occupy an intermediate value between the surface energy of the homopolymers. The additive nature of the change in the surface energy of the copolymers with their composition, as previously established in the works of Wu, extends to the dispersive component of the free surface energy γD and the critical surface energy γcr, according to Zisman. It was shown that a significant influence on the adhesive activity of copolymers was exerted by the substrate surface upon which the adhesive was formed. Thus, for the butadiene-nitrile copolymer (BNC) samples formed in contact with a high-energy substrate, their surface energy growth was associated with a significant increase in the polar component of the surface energy γP from 2 mJ/m2 for the samples formed in contact with air, to an increase from 10 to 11 mJ/m2 for the samples formed in contact with Al. The reason why the interface influenced the change in the energy characteristics of the adhesives was the selective interaction of each macromolecule fragment with the active centres of the substrate surface. As a result, the composition of the boundary layer changed and it became enriched with one of the components. The structure of such layers is nonequilibrium. The thermal annealing of copolymers in the mode of a stepwise temperature increase led to a convergence in the values of γ, asymptotically tending to the value characteristic of the surface of the copolymers formed in air. The activation energies for the processes of the conformational rearrangements of the macromolecules in the surface layers of the copolymers were calculated. It was found that the conformational rearrangements of the macromolecules in the surface layers occurred as a result of the internal rotation of the functional groups that determined the polar component of the surface energy.

Synthesis of methacrylic acid-acrylonitrile alternating copolymer using an extremely bulky methacrylate and the sequence-dependent thermal reaction behaviors

In this work, we achieved the synthesis of the alternating copolymer composed of commodity monomer units, methacrylic acid (MAA) and acrylonitrile (AN), by using a bulky and transformable methacrylate carrying 2-ethylfenchyl ester group (EFMA). The low propensity of EFMA in radical homopolymerization and the high reactivity of AN radical to methacrylate monomer in radical copolymerization allowed the peculiar alternating propagation, which was supported by the low reactivity ratios [r1 = 0.03, r2 = 0.23 for EFMA (M1) and AN (M2)]. The resultant EFMA-AN alternating copolymer was quantitatively transformed into the MAA-AN counterpart via acidolysis, as supported by 1H and 13C NMR analyses in comparison with the corresponding 1:1 statistical copolymer. The MAA-AN alternating copolymer underwent thermal reaction between neighboring pendant groups in alternating sequence, which was different from the statistical copolymer composed of various sequence patterns.

Ultrasmall, elementary and highly translational nanoparticle X-ray contrast media from amphiphilic iodinated statistical copolymers.

To expand the single-dose duration over which noninvasive clinical and preclinical cancer imaging can be conducted with high sensitivity, and well-defined spatial and temporal resolutions, a facile strategy to prepare ultrasmall nanoparticulate X-ray contrast media (nano-XRCM) as dual-modality imaging agents for positron emission tomography (PET) and computed tomography (CT) has been established. Synthesized from controlled copolymerization of triiodobenzoyl ethyl acrylate and oligo(ethylene oxide) acrylate monomers, the amphiphilic statistical iodocopolymers (ICPs) could directly dissolve in water to afford thermodynamically stable solutions with high aqueous iodine concentrations (>140mg iodine/mL water) and comparable viscosities to conventional small molecule XRCM. The formation of ultrasmall iodinated nanoparticles with hydrodynamic diameters of ca. 10nm in water was confirmed by dynamic and static light scattering techniques. In a breast cancer mouse model, invivo biodistribution studies revealed that the 64Cu-chelator-functionalized iodinated nano-XRCM exhibited extended blood residency and higher tumor accumulation compared to typical small molecule imaging agents. PET/CT imaging of tumor over 3 days showed good correlation between PET and CT signals, while CT imaging allowed continuous observation of tumor retention even after 10 days post-injection, enabling longitudinal monitoring of tumor retention for imaging or potentially therapeutic effect after a single administration of nano-XRCM.