Self-assembled Architectures Research Articles

Systematic Analysis of Self-Assembled Nanodielectric Architecture and Organization Effects on Organic Transistor Switching

The unconventional self-assembled nanodielectric (SAND) architecture is composed of solution-processed alternating inorganic (e.g., ZrOx and HfOx) and π-organic nanolayers (e.g., stilbazolium). As gate dielectrics, SANDs are compatible with a wide variety of organic and inorganic semiconductors and often impart superior thin-film transistor (TFT) performance in comparison to analogous inorganic-only dielectrics. The enhanced performance has been partly attributed to the interactions within the organic layers. To probe the role of the highly polarizable stilbazolium (Chr) organic layer in SAND structural organization and dielectric response, a saturated hydrocarbon chain-based self-assembling building block (Alk) was synthesized and incorporated in SAND structures. By using Chr and Alk in the different SAND organic layers, the effects of the Chr built-in dipole on bulk SAND structural and dielectric characteristics can be evaluated. The Zr-SAND structures are characterized by atomic force microscopy, X-ray reflectivity, metal-insulator-semiconductor electrical measurements, and pentacene-based organic TFTs. The layer identity and arrangement of the organic layers within the Zr-SAND structure are found to have a significant impact on the capacitor leakage current and pentacene transistor threshold voltage/turn-on voltage characteristics. Furthermore, significant cooperative interactions between adjacent Chr organic π-layers are important in enhancing these effects.

Tensional twist-folding of sheets into multilayered scrolled yarns.

Twisting sheets as a strategy to form functional yarns relies on millennia of human practice in making catguts and fabric wearables, but it still lacks overarching principles to guide their intricate architectures. We show that twisted hyperelastic sheets form multilayered self-scrolled yarns, through recursive folding and twist localization, that can be reconfigured and redeployed. We combine weakly nonlinear elasticity and origami to explain the observed ordered progression beyond the realm of perturbative models. Incorporating dominant stretching modes with folding kinematics, we explain the measured torque and energetics originating from geometric nonlinearities due to large displacements. Complementarily, we show that the resulting structures can be algorithmically generated using Schläfli symbols for star-shaped polygons. A geometric model is then introduced to explain the formation and structure of self-scrolled yarns. Our tensional twist-folding framework shows that origami can be harnessed to understand the transformation of stretchable sheets into self-assembled architectures with a simple twist.

Intermediate-induced repolymerization for constructing self-assembly architecture: Red crystalline carbon nitride nanosheets for notable hydrogen evolution

Few-layered polymeric carbon nitride (PCN) nanosheets with large specific surface area and effective charge/electron transport pathway have emerged as promising photocatalysts. However, PCN nanosheets normally exhibit enlarged bandgap, structural defects, and easy agglomeration. Herein, we report an intermediate-induced strategy for synthesizing red PCN nanosheets with a crystalline free self-assembly (CFSA) architecture, exhibiting a three-dimensional (3D) structure, minimum structural defects, small curved nanosheet subunits, and abundant reactive sites. The careful tuning of the condensation degree and repolymerization ability of intermediates affords CFSA PCN with an optimal 3D structure and optical properties, enabling the synergistic optimization of light absorption, charge mobility, and surface reactions during photocatalysis. The catalyst shows a superior H2 evolution rate of 14665 μmol g−1 h−1 (Pt 1.1 wt%), outperforming those of pristine bulk and nanosheet-structured PCN. This work provides a facile intermediate-induced strategy for guiding the design and synthesis of novel PCN-based photocatalysts.

How perfluoroalkyl substances modify fluorinated self-assembled monolayer architectures: An electrochemical and computational study

There is an urgent need for sensing strategies to screen perfluoroalkyl substances (PFAS) in aqueous matrices. These strategies must be applicable in large-scale monitoring plans to face the ubiquitous use of PFAS, their wide global spread, and their fast evolution towards short-chain, branched molecules. To this aim, the changes in fluorinated self-assembled monolayers (SAM) with different architectures (pinholes/defects-free and with randomized pinholes/defects) were studied upon exposure to both long and short-chain PFAS. The applicability of fluorinated SAM in PFAS sensing was evaluated. Changes in the SAM structures were characterised combining electrochemical impedance spectroscopy and voltammetric techniques. The experimental data interpretation was supported by molecular dynamics simulations to gain a more in-depth understanding of the interaction mechanisms involved. Pinhole/defect-free fluorinated SAM were found to be applicable to long-chain PFAS screening within switch-on sensing strategy, while a switch-off sensing strategy was reported for screening of both short/long-chain PFAS. These strategies confirmed the possibility to play on fluorophilic interactions when designing PFAS screening methods.

Fmoc-protected amino acids as luminescent and circularly polarized luminescence materials based on charge transfer interaction

Fluorenylmethyloxycarbonyl (Fmoc)-protected amino acids are effective building blocks in self-assembled architectures at hierarchical levels, which however show limited luminescent properties and chiroptical activities. Here we introduce a charge-transfer strategy to build two-component luminescent materials with emerged circularly polarized luminescence properties. A library of Fmoc-amino acids was built, which selectively form charge-transfer complexes with the electron-deficient acceptor. Embedding in amorphous polymer matrix or physical grinding could trigger the charge-transfer luminescence with adjusted wavelengths in a general manner. X-ray diffraction results suggest the multiple binding modes between donor and acceptor. And, the solution-processed coassembly could selectively exhibit circularly polarized luminescence with high dissymmetry g-factors. This work illustrates a noncovalent charge-transfer strategy to construct luminescent and chiroptical organic composites based on the easy-accessible and economic chiral N-terminal aromatic amino acids.

Stereodivergent Chirality Transfer by Noncovalent Control of Disulfide Bonds.

Controlling dynamic stereochemistry is an important challenge, as it is not only inherent to protein structure and function but often governs supramolecular systems and self-assembly. Typically, disulfide bonds exhibit stereodivergent behavior in proteins; however, how chiral information is transmitted to disulfide bonds remains unclear. Here, we report that hydrogen bonds are essential in the control of disulfide chirality and enable stereodivergent chirality transfer. The formation of S–S···H–N hydrogen bonds in solution can drive conformational adaption to allow intramolecular chirality transfer, while the formation of C=O···H–N hydrogen bonds results in supramolecular chirality transfer to form antiparallel helically self-assembled solid-state architectures. The dependence on the structural information encoded in the homochiral amino acid building blocks reveals the remarkable dynamic stereochemical space accessible through noncovalent chirality transmission.

Engineering NH3-induced 1D self-assembly architecture with conductive polymer for advanced hybrid Na-CO2 batteries via morphology modulation

Designing catalytic cathodes with excellent electrocatalytic activities and durability for Na-CO 2 batteries has captured considerable attention so far. Here, a series of morphologically controlled low-crystalline CuCo 2 O 4 was prepared by thermal oxidation of self-assembled Cu-Co precursors ( p -CCO). One-dimensional (1D) rod-like of CuCo 2 O 4 was subsequently encapsulated in polypyrrole shell (PPy) by in-situ polymerization of pyrrole monomers as an advanced catalyst (CCO/PPy) for high-performance Na-CO 2 batteries. It was demonstrated that ammonia solution exerts an important influence on the surface morphology and size of the p -CCO crystallites by the rate of nucleation and growth. Particle size and 1D architecture modulation, associated with the encapsulation of conductive PPy effectively improve the directional transfer rate of ions and the conductivity of the electrode. More importantly, PPy introduction not only induces interfacial reconstruction of CuCo 2 O 4 , arousing more oxygen vacancies and catalytic active sites, but also contributes to the corrosion protection of the active material from the electrolyte during long-term operation. Bestowed by these advantages, the fabricated hybrid Na-CO 2 battery manifested prominent electrochemical performance with a superior areal discharge capacity of 31.3 mAh cm −2 , low discharge-charge voltage gap of 0.6 V, over 400 cycles. • The 1D rod-like CuCo 2 O 4 with oxygen vacancies was obtained by morphology modulation. • A mechanism for the directional growth of NH 3 -induced Cu-Co precursors was proposed. • CCO/PPy exhibited enriched active sites with superior CRR and CER performance. • A high areal capacity of 31.3 mAh·cm −2 and over 400 cycles were achieved.

Heterochirality-Mediated Cross-Strand Nested Hydrophobic Interaction Effects Manifested in Surface-Bound Peptide Assembly Structures.

Amino acid chirality has been envisioned as an important strategy to regulate structure and function of peptide self-assembled architectures. However, the molecular mechanism of chirality effects in peptide assemblies remains largely elusive. Here, the assembly structures of l-peptide polyphenylalanine F10 (FFFFFFFFFF) and block heterochiral peptide F5f5 (FFFFFfffff) composed of two FFFFF repeat blocks with opposite chirality were characterized at the single-molecule level by using scanning tunneling microscopy. Each peptide formed two distinctively different assembly structures on the HOPG surface, in which peptide chains took parallel and antiparallel β-sheet conformations, respectively. The molecular-level observations revealed that the staggered arrangement of cross-strand side chains achieved in the antiparallel β-sheet structure of the block heterochiral peptide facilitated intimate packing of side chains and maximized inter-residue van der Waals interactions, which led to more residues participating in assembly and greatly stabilized the β-sheet structure of the surface-bound peptide assembly, but such cross-strand nested interactions were not accessible in the heterochiral parallel β-sheet structure and the enantiomerically pure assembly structures. This work could contribute to the molecular insights of stereochemical interactions in peptide assemblies and feasibility of extending this block heterochirality pattern to other peptides with various lengths and amino acid compositions for structural regulations.

Templation and Concentration Drive Conversion Between a FeII12L12 Pseudoicosahedron, a FeII4L4 Tetrahedron, and a FeII2L3 Helicate.

We report the construction of three structurally distinct self-assembled architectures: FeII12L12 pseudoicosahedron 1, FeII2L3 helicate 2, and FeII4L4 tetrahedron 3, formed from a single triazatriangulenium subcomponent A under different reaction conditions. Pseudoicosahedral capsule 1 is the largest formed through subcomponent self-assembly to date, with an outer-sphere diameter of 5.4 nm and a cavity volume of 15 nm3. The outcome of self-assembly depended upon concentration, where the formation of pseudoicosahedron 1 was favored at higher concentrations, while helicate 2 exclusively formed at lower concentrations. The conversion of pseudoicosahedron 1 or helicate 2 into tetrahedron 3 occurred following the addition of a CB11H12– or B12F122– template.

A bottom-up design strategy for controllable self-assembly based on the isotropic double-well potential.

Controllable self-assembly of particles or atoms is still challenging in the synthesis of materials with desirable properties that are highly relevant to the microscopic structures determined by the interparticle interactions. To gain insight into how the interactions affect the self-assembly, we designed various kinds of isotropic double-well potentials and simulated the motion of the particles. By controlling the depth and location of the potential wells and the height of the barriers, we studied their effects on the aggregation structures and the related microscopic kinetic processes. We identified five aggregation patterns at different temperatures and eight kinds of crystals, including Frank-Kasper phases, and observed the expansion or contraction of crystals. We found that the system usually stays in a sparse configuration at very low or very high temperatures. The particles typically assemble into a loosely packed cluster at medium temperatures and then deplete into a tightly packed state with a specific pattern. These phenomena can be explained from the perspective of energy. In contrast, very few structures could be obtained for the system guided by a single-well potential under the same simulation conditions. Thus, the interparticle interactions driven by the double-well potential greatly enrich the possible packing morphology of the system. The information obtained from this work helps us to understand how to achieve a specific self-assembled architecture through a reasonable selection of materials.

Shape dependent photocatalytic H2 evolution of a zinc porphyrin.

Hydrogen is regarded as a promising molecular fuel in order to produce clean energy, thus it is of great importance to produce and store H2 in order to replace fossil fuels and to resolve the global energy and environmental problems. One strategy to produce hydrogen is the photocatalytic splitting of water. In this study different supramolecular architectures of a Zn(II) porphyrin, showing "flower", octahedral and "manta ray" shaped structures, were obtained using the "good-bad" solvent self-assembly protocol. More specifically, the bad solvent (methanol) was retained and the good solvent was alerted obtaining diverse assemblies. The different structures were studied by scanning electron microscopy, PXRD, UV-Vis and IR spectroscopies. The prepared structures were capable of proton reduction and production of molecular H2 in the presence of 5% w/w Pt-nanoparticles as catalysts and ascorbic acid as a sacrificial electron donor. Moreover, depending on the structure of the chromophore that is formed the amount of H2 produced varies. The maximum H2 production was obtained with the octahedral structures (185.5 μmol g-1 h-1).

Heterocycle‐modified 2′‐Deoxyguanosine Nucleolipid Analogs Stabilize Guanosine Gels and Self‐assemble to Form Green Fluorescent Gels

Nucleoside-lipid conjugates are very useful supramolecular building blocks to construct self-assembled architectures suited for biomedical and material applications. Such nucleoside derivatives can be further synthetically manipulated to endow additional functionalities that could augment the assembling process and impart interesting properties. Here, we report the design, synthesis and self-assembling process of multifunctional supramolecular nucleolipid synthons containing an environment-sensitive fluorescent guanine. The amphiphilic synthons are composed of an 8-(2-(benzofuran-2-yl)vinyl)-guanine core and alkyl chains attached to 3'-O and 5'-O-positions of 2'-deoxyguanosine. The 2-(benzofuran-2-yl)vinyl (BFV) moiety attached at the C8 position of the nucleobase adopted a syn conformation about the glycosidic bond, which facilitated the self-assembly process through the formation of a G-tetrad as the basic unit. While 3',5'-diacylated BFV-modified dG analog stabilized the guanosine hydrogel by hampering the crystallization process and imparted fluorescence, BFV-modified dGs containing longer alkyl chains formed a green fluorescent organogel, which transformed into a yellow fluorescent gel in the presence of a complementary non-fluorescent cytidine nucleolipid. The ability of the dG analog containing short alkyl chains to modulate the mechanical property of a gel, and interesting fluorescence properties and self-assembling behavior exhibited by the dG analogs containing long alkyl chains in response to heat and complementary base underscore the potential use of these new supramolecular synthons in material applications.

Novel Tough and Transparent Ultra-Extensible Nanocomposite Elastomers Based on Poly(2-methoxyethylacrylate) and Their Switching between Plasto-Elasticity and Viscoelasticity.

Novel stiff, tough, highly transparent and ultra-extensible self-assembled nanocomposite elastomers based on poly(2-methoxyethylacrylate) (polyMEA) were synthesized. The materials are physically crosslinked by small in-situ-formed silica nanospheres, sized 3–5 nm, which proved to be a very efficient macro-crosslinker in the self-assembled network architecture. Very high values of yield stress (2.3 MPa), tensile strength (3.0 MPa), and modulus (typically 10 MPa), were achieved in combination with ultra-extensibility: the stiffest sample was breaking at 1610% of elongation. Related nanocomposites doubly filled with nano-silica and clay nano-platelets were also prepared, which displayed interesting synergy effects of the fillers at some compositions. All the nanocomposites exhibit ‘plasto-elastic’ tensile behaviour in the ‘as prepared’ state: they display considerable energy absorption (and also ‘necking’ like plastics), but at the same time a large but not complete (50%) retraction of deformation. However, after the first large tensile deformation, the materials irreversibly switch to ‘real elastomeric’ tensile behaviour (with some creep). The initial ‘plasto-elastic’ stretching thus causes an internal rearrangement. The studied materials, which additionally are valuable due to their high transparency, could be of application interest as advanced structural materials in soft robotics, in implant technology, or in regenerative medicine. The presented study focuses on structure-property relationships, and on their effects on physical properties, especially on the complex tensile, elastic and viscoelastic behaviour of the polyMEA nanocomposites.

Backbone extension via peptidomimetics at N-terminal; self-assembled nanofibrous cluster and application to selective progesterone detection in an aqueous medium

Despite the adequacy of the endogenous steroid (progesterone) levels in biological functioning, elevated levels of progesterone hormone have several physiological effects that are amplified due to its direct and indirect uptake from the environment, food products, and medical therapy. So, it is much needed to evaluate the progesterone levels in environmental samples as well as for biological fluids. In this work, we focused on the development of the nano sensing probe for the selective detection of progesterone among the library of steroid hormones belonging to the class of female sex hormones. Herein, functionalization of dipeptide is carried out at N-terminal to produce N-functionalized dipeptide (SS3), and simultaneously, its self-assembly properties are explored. Furthermore, HR-TEM imaging was also performed to examine the morphology of the self-assembled architectures before and after the addition of the steroid hormone. To investigate the binding mechanism of the sensing probe, Fluorescence spectroscopy, Circular Dichroism (CD), MD-Simulation, and DFT studies were performed and studied in detail. Moreover, to check the potency of the real-time application of the developed nanoprobe, we have successfully determined the spiked concentration of progesterone levels in pharmaceutical and biological fluid samples with functional percentage recovery. Also, the stability and other competitive binding studies of the probe with the coexisting substances are performed to check the rationality of the sensing probe at physiological conditions.

Bioinspired Quasi-3D Multiplexed Anti-Counterfeit Imaging via Self-Assembled and Nanoimprinted Photonic Architectures.

Innovative multiplexing technologies based on nano-optics for anti-counterfeiting have been proposed as overt and covert technologies to secure products and make them difficult to counterfeit. However, most of these nano-optical anti-counterfeiting materials are metasurfaces and metamaterials with complex and expensive fabrication process, often resulting in materials that are not damage tolerant. Highly efficient anti-counterfeiting technologies with easy fabrication process are targeted for intuitive and effective authentication of banknotes, secure documents, and goods packing. Here, a simple strategy exploiting self-assembling and nanoimprinting technique to fabricate a composite lattice photonic crystal architecture featuring full spatial control of light, multiplexed full-pixel imaging, and multichannel cryptography combined with customized algorithms is reported. In particular, the real-time encryption/recognition of mobile quick response codes and anti-counterfeiting labels on a postage stamp, encoded by the proposed photonic architecture, are both demonstrated. The wave optics of scattering, diffraction, and polarization process involved are also described, validated with numerical simulations and experiments. By introducing a new degree of freedom in the 3D space, the multichannel image switching exhibits unprecedented variability of encryption, providing a promising roadmap to achieve larger information capacity, better security, and higher definition for the benefit of modern anti-counterfeiting security.

3D Steric Bulky Semiconductor Molecules toward Organic Optoelectronic Nanocrystals

With minimal defects, few grain boundaries, and high-performance optoelectronic characteristics, organic semiconductor nanocrystals (OSNCs) have emerged as promising solutions for miniaturized organic devices and related optoelectronic circuits. To realize this, it is crucial that the OSNCs should possess desired morphologies and unique optoelectronic attributions. After the planar π-conjugated building blocks, the steric bulky molecules with a three-dimensional (3D) framework enable the multiscale self-assembly architectures and superior charge storage properties, as well as high-performance optoelectronic applications, such as organic transistor memory, organic light-emitting diodes, organic lasers and organic photovoltaic cells. However, this type of 3D steric bulky molecule-based OSNCs are not easily to get, and molecular design principles must be developed. In this Review, recent advances in the efficient theories that have arose in building varied nanoarchitectures of 3D steric bulky molecule-based OSNCs, especially the 2D and 3D in morphology, are highlighted. The obtained steric OSNCs exhibited rich optoelectronic properties, including the charge storage, ion transmission, crystallization-enhanced emission, and so on. Further architectural optimization of the steric OSNCs to cater for optoelectronic device based on them is necessary to strive to develop this research direction.

γ-AApeptides as a New Class of Peptidomimetics: Design, Synthesis, and Applications.

Peptidomimetics are studied for medicinal application because of their ability to mimic hierarchical structures of peptides and proteins. To break the limitation and expand the peptidomimetics family, a new class of peptidomimetics based on peptide nucleic acids (PNAs) backbone - "γ-AApeptides" was developed. Compared with previous peptidomimetics, γ-AApeptides possess prominent advantages such as resistance to proteolytic degradation, enhanced chemodiversity, good selectivity and outstanding bioactivity. The synthesis of γ-AApeptides is carried out using a ''monomer building block'' strategy which is facile and efficient. γ-AApeptides are able to mimic primary and secondary structures of therapeutic peptides, which make them promising candidates for molecular probes and potential drug leads. In the past decade, several interesting structures and applications of γ-AApeptides have been developed by different approaches such as structure-based design, combinatorial library screening, and peptides selfassembly and folding. By following the mechanism of host-defense peptides (HDPs), antibiotic γ- AApeptides showed broad-spectrum activity. At the same time, γ-AApeptides can be used for combinatorial library screening because of their structural stability and their chemodiversity. Anticancer agents, anti-T2DM (Type 2 diabetes mellitus) agents, anti-HIV (human immuno-deficiency virus) agents and anti-Alzheimer's disease agents were developed by combinatorial screening and rational design. Furthermore, γ-AApeptides as biopolymers, nanomaterials, supramolecular structures and self-assembly architectures were studied due to their unique backbone structures. Therefore, γ-AApeptides may play an important role in the development of peptidomimetics.

Phenylalanine Interacts with Oleic Acid-Based Vesicle Membrane. Understanding the Molecular Role of Fibril–Vesicle Interaction under the Context of Phenylketonuria

In the present contribution, on the basis of a spectroscopic and microscopic investigation, the characterization and photophysics of various assemblies of oleic acid/oleate solution at three pH values, namely, 8.28, 9.72, and 11.77, were explored. The variation in the dynamic response of aqua molecules in and around the assemblies has been interrogated by a picoseconds solvation dynamics experiment using a time-correlated single-photon counting setup employing coumarin-153 as a probe. On the one hand, the time-resolved fluorescence anisotropy measurement along with the fluorescence correlation spectroscopy experiment was executed to extract information regarding the comparison of the extent of the internal restricted confinement of these assemblies. On the other hand, an effort to investigate the cross-interaction between the self-assembled architectures of l-phenylalanine (l-Phe), responsible for phenylketonuria (PKU) disorder, and the oleic acid at the vesicle-forming pH established that the l-Phe fibrillar morphologies strongly alter the dynamic properties of the vesicle membrane formed by the oleic acid. Specifically, the interaction of the l-Phe assemblies with the oleic acid vesicle membrane is found to introduce the flexibility of the vesicle membrane and alter the hydration properties of the membrane. To track the fibril-induced alterations of the oleic acid vesicle properties, various spectroscopic and microscopic investigations were performed. The mutual reconciliation of the experimental outputs, therefore, portrays the state of the art, which accounts for the fibril-induced alterations of the properties of the oleic acid vesicle membrane, the mimicking setup of the cellular membrane, thereby informing us that alterations of such a property of the membrane should be taken into active consideration during the rational development of therapeutic modulators against disorders like PKU.

Cell medium-dependent dynamic modulation of size and structural transformations of binary phospholipid/ω-3 fatty acid liquid crystalline nano-self-assemblies: Implications in interpretation of cell uptake studies

Lyotropic non-lamellar liquid crystalline (LLC) nanoparticles, with their tunable structural features and capability of loading a wide range of drugs and reporter probes, are emerging as versatile injectable nanopharmaceuticals. Secondary emulsifiers, such as Pluronic block copolymers, are commonly used for colloidal stabilization of LLC nanoparticles, but their inclusion often compromises the biological safety (e.g., poor hemocompatibility and enhanced cytotoxicity) of the formulation. Here, we introduce a library of colloidally stable, structurally tunable, and pH-responsive lamellar and non-lamellar liquid crystalline nanoparticles from binary mixtures of a phospholipid (phosphatidylglycerol) and three types of omega-3 fatty acids (ω-3 PUFAs), prepared in the absence of a secondary emulsifier and organic solvents. We study formulation size distribution, morphological heterogeneity, and the arrangement of their internal self-assembled architectures by nanoparticle tracking analysis, synchrotron small-angle X-ray scattering, and cryo-transmission electron microscopy. The results show the influence of type and concentration of ω-3 PUFAs in nanoparticle structural transitions spanning from a lamellar (Lα) phase to inverse discontinuous (micellar) cubic Fd3m and hexagonal phase (H2) phases, respectively. We further report on cell-culture medium-dependent dynamic fluctuations in nanoparticle size, number and morphology, and simultaneously monitor uptake kinetics in two human cell lines. We discuss the role of these multiparametric biophysical transformations on nanoparticle-cell interaction kinetics and internalization mechanisms. Collectively, our findings contribute to the understanding of fundamental steps that are imperative for improved engineering of LLC nanoparticles with necessary attributes for pharmaceutical development.

Etherified pullulan-polyethylenimine based nanoscaffolds improved chemosensitivity of erlotinib on hypoxic cancer cells.

The current research endeavor aimed to accomplish hypoxia-responsive polyethyleneimine-conjugated carboxymethyl pullulan-based co-polymer (CMP-HA-NI-PEI-NBA) bearing nitroaromatic subunits to efficiently deliver erlotinib (ERL) to reverse its hypoxia-induced resistance in cancer cells. As compared to a control co-polymer (CMP-HA-MI-PEI-BA) devoid of hypoxia-sensitive moieties, this scaffold demonstrated a hypochromic shift in the UV spectra and rapid dismantling of its self-assembled architecture upon exposure to simulated hypoxic condition. The hypoxia-responsive co-polymer encapsulated ERL with desirable loading capacity (DEE, 63.05 ± 2.59%), causing attenuated drug crystallinity. The drug release rate of the scaffold under reducing condition was faster relative to that of non-reducing environment. Their cellular uptake occurred through an energy-dependent endocytic process, which could exploit its caveolae/lipid raft-mediated internalization pathway. The ERL-loaded scaffolds more efficiently induced apoptosis and suppressed the proliferation of drug-resistant hypoxic HeLa cells than the pristine ERL. Hence, this study presented a promising drug delivery nanoplatform to overcome hypoxia-evoked ERL resistance.