Fluorescence sensing probe based on functionalized mesoporous MOFs for non-invasive and detection of dopamine in human fluids.

Abnormal amount of dopamine (DA) in human body is closely relate to various diseases, such as Parkinson's disease, pheochromocytoma. Real-time monitoring DA is crucial for disease warning, diagnosis and treatment. Currently, most methods rely on invasive blood testing for detecting DA, which is only completed with the aid of the medical staffs in hospitals. Herein, a non-invasive fluorescence visual strategy is developed for the real-time monitoring DA, based on luminescent nanoparticles and modified mesoporous zeolite imidazole framework (ZIF-8-NH2) dodecahedrons. During the reaction process, DA is enriched through the spatial configuration of ZIF-8-NH2 and hydrogen bonding effect. The luminescence of Cr3+-doped zinc gallate (ZnGa2O4:Cr3+, ZGC) is inhibited by the photo-induced electron transfer (PET) mechanism to realize sensitively detecting DA. The intelligent sensing platform based on the designed fluorescence probe and color recognition system is structured for real-time detection of DA in urine. Furthermore, a skin-fitting hydrogel patch is prepared by combining a fluorescent probe with chitosan, which enables sensitive and accurate detection of DA in sweat without the complex sample pretreatment. The non-invasive fluorescence detection method provides an effective strategy for quantitatively monitoring DA in human fluids.

Introduction of a Novel Structure for a Light Unmanned Free Balloon's Payload: A Comprehensive Hybrid Study.

Payloads for light unmanned free balloons must meet several safety requirements such as being able to protect the inner electronics in order to extract scientific data and to reduce the chance of inflicting personal injury in case of an accidental fall. This article proposes a novel payload structure, which exhibits the form of a dodecahedron. The actual form was determined by carrying out theoretical drop tests on different polyhedrons using the finite element method (FEM). From the simulations, it could be deduced that the dodecahedron was the optimal choice, since the duration of the impact was longer, while the impact force was slightly lower. The payload was produced by additive technologies; therefore, after performing tensile tests on probable materials, PLA was selected as the optimal candidate. The theoretical results about the dodecahedron's ability were validated by laboratory and real-life drop tests, where the new payload was subjected to 56% less impact force under a 78% longer collision time compared to a classic, rectangular cuboid design. Based on these tests, it was demonstrated that the new structure is safer and it is applicable.

African swine fever virus A137R assembles into a dodecahedron cage.

African swine fever (ASF) is a highly contagious viral disease that affects domestic and wild pigs. The causative agent of ASF is African swine fever virus (ASFV), a large double-stranded DNA virus with a complex virion structure. Among the various proteins encoded by ASFV, A137R is a crucial structural protein associated with its virulence. However, the structure and molecular mechanisms underlying the functions of A137R remain largely unknown. In this study, we present the structure of A137R determined by cryogenic electron microscopy single-particle reconstruction, which reveals that A137R self-oligomerizes to form a dodecahedron-shaped cage composed of 60 polymers. The dodecahedron is literally equivalent to a T = 1 icosahedron where the icosahedral vertexes are located in the center of each dodecahedral facet. Within each facet, five A137R protomers are arranged in a head-to-tail orientation with a long N-terminal helix forming the edge through which adjacent facets stitch together to form the dodecahedral cage. Combining structural analysis and biochemical evidence, we demonstrate that the N-terminal domain of A137R is crucial and sufficient for mediating the assembly of the dodecahedron. These findings imply the role of A137R cage as a core component in the icosahedral ASFV virion and suggest a promising molecular scaffold for nanotechnology applications. IMPORTANCE: African swine fever (ASF) is a lethal viral disease of pigs caused by African swine fever virus (ASFV). No commercial vaccines and antiviral treatments are available for the prevention and control of the disease. A137R is a structural protein of ASFV that is associated with its virulence. The discovery of the dodecahedron-shaped cage structure of A137R in this study is of great importance in understanding ASFV pathogenicity. This finding sheds light on the molecular mechanisms underlying the functions of A137R. Furthermore, the dodecahedral cage formed by A137R shows promise as a molecular scaffold for nanoparticle vectors. Overall, this study provides valuable insights into the structure and function of A137R, contributing to our understanding of ASFV and potentially opening up new avenues for the development of vaccines or treatments for ASF.

Crystal structure of a layered phosphate molybdate K2Gd(PO4)(MoO4).

The title compound dipotassium gadolinium(III) phosphate(V) molybdate(VI), K2Gd(PO4)(MoO4), was synthesized from a high-temperature melt starting from GdF3 as a source of gadolinium. Its structure is isotypic with other M I 2 M III(M VIO4)(PO4) compounds, where M I = Na, K or Cs, and M III = rare-earth cation, M VI = Mo or W. The three-dimensional framework is built up from [Gd(PO4)(MoO4)] anionic sheets, which are organized by adhesion of [GdPO4] layers and [MoO4] tetra-hedra stacked above and below these layers. The inter-stitial space is occupied by K cations having eightfold oxygen coordination. The polyhedron of GdO8 was estimated to be a triangular dodeca-hedron by the continuous shape measurement method.

Self-Assembly of Polyoxometalate-Based Sub-1†nm Polyhedral Building Blocks into Rhombic Dodecahedral Superstructures.

Self-assembly of subnanometer (sub-1 nm) scale polyhedral building blocks can yield some superstructures with novel and interesting morphology as well as potential functionalities. However, achieving the self-assembly of sub-1 nm polyhedral building blocks is still a great challenge. Herein, through encapsulating the titanium-substituted polyoxometalate (POM, K7 PTi2 W10 O40 ) with tetrabutylammonium cations (TBA+ ), we first synthesized a sub-1 nm rhombic dodecahedral building block by further tailoring the spatial distribution of TBA+ on the POM. Molecular dynamics (MD) simulations demonstrated the eight TBA+ cations interacted with the POM cluster and formed the sub-1 nm rhombic dodecahedron. As a result of anisotropy, the sub-1 nm building blocks have self-assembled into rhombic dodecahedral POM (RD-POM) assemblies at the microscale. Benefiting from the regular structure, Br- ions, and abundant active sites, the obtained RD-POM assemblies exhibit excellent catalytic performance in the cycloaddition of CO2 with epoxides without co-catalysts. This work provides a promising approach to tailor the symmetry and structure of sub-1 nm building blocks by tuning the spatial distribution of ligands, which may shed light on the fabrication of superstructures with novel properties by self-assembly.

An electrochemical sensor for purine base detection with ZIF-8-derived hollow N-doped carbon dodecahedron and AuNPs as electrocatalysts.

In this paper, a novel electrochemical sensor was constructed for the detection of purine bases. Ultrafine carbide nanocrystals confined within porous nitrogen-doped carbon dodecahedrons (PNCD) were synthesized by adding molybdate to ZIF-8 followed by annealing. With MoC-based PNCDs (MC-PNCDs) as the carrier, gold nanoparticles (AuNPs) were deposited on the electrode surface via potentiostatic deposition as the promoter of electron transfer, forming a AuNPs/MC-PNCDs/activated glassy carbon electrode (AGCE) sensor. MC-PNCDs had a large specific surface area, which combined with the excellent electrocatalytic activity of AuNPs, synergistically improved the electrocatalytic activity. The morphology and structure of the electrode surface modifier were characterized by scanning electron microscopy, transmission electron microscopy, energy-dispersive X-ray photoelectron spectroscopy, infrared spectroscopy, X-ray diffraction, nitrogen adsorption-desorption analysis, and electrochemical characterization. Under the optimal conditions, the linear detection range of guanine (G) and adenine (A) was 0.5-160.0 µM, and the detection limits (S/N=3) were 72.1 and 69.6 nM, respectively. AuNPs/MC-PNCDs/AGCE was successfully constructed, and was used to simultaneously detect G and A with high sensitivity and selectivity. Moreover, the sensor was successfully used to detect G and A in herring sperm DNA samples.

Core-shell CoCuOx@MOx (MNb, Ti and Ce) catalysts with outstanding durability and resistance to H2O for the catalytic combustion of o-dichlorobenzene.

Configuring Co-based catalysts with excellent activity, durability, anti-H2O capability and superior chlorine resistance is an effective strategy for catalytic combustion of CVOCs. In this work, we elaborated a CoCuOx catalysts with the same core but different shell. The CoCuOx dodecahedron surface was successfully coated with shells of Nb2O5, TiO2, and CeO2 using a range of conventional synthesis methods. The prepared core-shell catalysts (CoCuOx@TiO2 and CoCuOx@Nb2O5) were found to generate plentiful acid sites and abundant lattice oxygen species, indicating a strong interaction between the core and shell layers that resulted in a significant enhancement of catalytic activity. Additionally, by-products generation was successfully controlled by acid sites and lattice oxygen species. More importantly, the core-shell structure design significantly improved the thermal stability and anti-H2O capability of the catalysts. Furthermore, the possible formation pathways and reaction mechanisms were proposed based on in-situ FTIR and selectivity analysis.

Co-MOFs as Emerging Pulse Modulators for Femtosecond Ultrafast Fiber Laser.

The metal organic framework (MOF) has attracted more and more attention due to its unique morphology, functional linkers, and orderly network structure. Zeolitio imidazolata frameworks (ZIFs), which are formed by bivalent transition metals (Zn, Co, etc.) and nitrogen-containing heterocyclic imidazole or purine organic ligands, are a very attractive subclass of MOFs. ZIF-67, obtained by the nucleation growth of dimethylimidazole and Co 2p, has been developed as a precursor for porous nanostructured cobalt-based metal oxides. During material preparation we add rGO because it can be used as a basic element to construct macroscopic three-dimensional carbon structural materials, which self-assemble into a 3D network structure with ZIF-67 through simple van der Waals forces or hydrogen bonds, and some samples contain specific functional groups that are added to the precursor. In this paper, we employ liquid-phase synthesis to generate rGO-ZIF-67 and calcine it at the temperature of 350 °C to obtain rGO-Co3O4. Then we fabricate rGO-Co3O4 and rGO-ZIF-67 modulators based on microfibers and test their nonlinear optical absorption in 1.5 µm range. The modulation depths of rGO-Co3O4 and rGO-ZIF-67 are measured as 10.41% and 6.61%, respectively. By using microfiber-based rGO-Co3O4 modulator, we have obtained a conventional soliton and a soliton molecule in Er3+-doped fiber lasers. The conventional soliton has a pulse width of 793.4 fs and a spectral width of 3.3 at 1558.9 nm, respectively. The obtained soliton molecule has a spectral modulation period of 1.65 nm and temporal separation of 4.94 ps at 1563.2 nm. By employing a microfiber-based rGO-ZIF-67 modulator, we obtain conventional solitons with a spectral width of 1.9 nm at the central wavelength of 1529.8 nm. Our research may expand the MOF-based materials for ultrafast photonics, blazing a new path for fiber laser, optical communications, and optoelectronics, etc.

Hollow C-LDH/Co9S8 nanocages derived from ZIF-67-C for high- performance asymmetric supercapacitors.

The design of supercapacitor electrode materials greatly depends on the rational construction of nanostructures and the effective combination of different active materials. Due to the poor electrical conductivity and mechanical strength, nickel-cobalt double hydroxide (NiCo-LDH) cannot reach the theoretical high specific capacitance value, while Co9S8 shows many interesting features, such as excellent electrochemical properties, high conductivity, and greatly improved redox reactions. Therefore, we prepared ZIF-67-C derived hollow NiCo-LDH (C-LDH)/Co9S8 nanocages containing two components of Co9S8 and NiCo-LDH through a multistep transformation method. The prepared C-LDH/Co9S8 nanoparticles showed a hollow rhomboid dodecahedron structure, and many NiCo-LDH nanosheets were reasonably distributed on the surface. In the three-electrode test, it can be obtained that its specific capacitance is 1654 F·g-1 when current density is 2 A·g-1 and 82.5% capacitance retention after 5000 cycles. Moreover, asymmetric supercapacitors (ASCs) prepared with C-LDH/Co9S8 as cathode and AC as anode can achieve a large energy density of 47.3 Wh·kg-1 under the condition of high power density of 1505 W·kg-1. After 10,000 cycles, capacitance retention rate is 80.9%, exhibit excellent cycle performance, suggesting the great potential of hollow C-LDH/Co9S8 nanocages in the application of supercapacitors.

On the use of adenovirus dodecahedron as a carrier for glycoconjugate vaccines.

Virus-Like Particles (VLPs) have been used as immunogenic molecules in numerous recombinant vaccines. VLPs can also serve as vaccine platform to exogenous antigens, usually peptides incorporated within the protein sequences which compose the VLPs or conjugated to them. We herein described the conjugation of a synthetic tetrasaccharide mimicking the Streptococcus pneumoniae serotype 14 capsular polysaccharide to recombinant adenoviral type 3 dodecahedron, formed by the self-assembling of twelve penton bases and investigated the induced immune response when administered subcutaneously (s.c.). Whether formulated in the form of a dodecahedron or disassembled, the glycoconjugate induced an anti-protein response after two and three immunizations equivalent to that observed when the native dodecahedron was administered. On the other hand, the glycoconjugate induced a weak anti-IgM response which diminishes after two doses but no IgM-to-IgG switch was observed in mice against the serotype 14 capsular polysaccharide. In definitive, the whole conjugation process preserved both particulate nature and immunogenicity of the adenoviral dodecahedron. Further studies are needed to fully exploit adenoviral dodecahedron potential in terms of plasticity towards sequence engineering and of its capacity to stimulate the immune system via the intranasal route of administration as well as to shift the response to the carbohydrate antigen by playing both with the carbohydrate to protein ratio and the length of the synthetic carbohydrate antigen.

Evaluation of the human type 3 adenoviral dodecahedron as a vector to target acute myeloid leukemia.

Intensive systemic chemotherapy is the gold standard of acute myeloid leukemia (AML) treatment and is associated with considerable off-target toxicities. Safer and targeted delivery systems are thus urgently needed. In this study, we evaluated a virus-like particle derived from the human type 3 adenovirus, called the adenoviral dodecahedron (Dd) to target AML cells. The vectorization of leukemic cells was proved very effective at nanomolar concentrations in a time- and dose-dependent manner, without vector toxicity. The internalization involved clathrin-mediated energy-dependent endocytosis and strongly correlated with the expression of αVß3 integrin. The treatment of healthy donor peripheral blood mononuclear cells showed a preferential targeting of monocytes compared to lymphocytes and granulocytes. Similarly, monocytes but also AML blasts were the best-vectorized populations in patients while acute lymphoid leukemia blasts were less efficiently targeted. Importantly, AML leukemic stem cells (LSCs) could be addressed. Finally, Dd reached peripheral monocytes and bone marrow hematopoietic stem and progenitor cells following intravenous injection in mice, without excessive spreading in other organs. These findings reveal Dd as a promising myeloid vector especially for therapeutic purposes in AML blasts, LSCs, and progenitor cells.

The Adenovirus Dodecahedron: Beyond the Platonic Story.

Many geometric forms are found in nature, some of them adhering to mathematical laws or amazing aesthetic rules. One of the best-known examples in microbiology is the icosahedral shape of certain viruses with 20 triangular facets and 12 edges. What is less known, however, is that a complementary object displaying 12 faces and 20 edges called a 'dodecahedron' can be produced in huge amounts during certain adenovirus replication cycles. The decahedron was first described more than 50 years ago in the human adenovirus (HAdV3) viral cycle. Later on, the expression of this recombinant scaffold, combined with improvements in cryo-electron microscopy, made it possible to decipher the structural determinants underlying their architecture. Recently, this particle, which mimics viral entry, was used to fish the long elusive adenovirus receptor, desmoglein-2, which serves as a cellular docking for some adenovirus serotypes. This breakthrough enabled the understanding of the physiological role played by the dodecahedral particles, showing that icosahedral and dodecahedral particles live more than a simple platonic story. All these points are developed in this review, and the potential use of the dodecahedron in therapeutic development is discussed.

Tunable Hollow Pt@Ru Dodecahedra via Galvanic Replacement for Efficient Methanol Oxidation.

Pt-Ru nanocrystals are promising electrocatalysts for methanol oxidation in fuel cells. However, owing to the lattice mismatch and high reduction potential of Ru, the shape-controlled synthesis of Pt-Ru nanocrystals faces great challenges. Herein, we employ a galvanic replacement method to synthesize tunable hollow Pt@Ru dodecahedra via controlling the precursor concentration. Two typical structures, hollow Pt@Ru dodecahedra (h-Pt@Ru) and deformed hollow Pt@Ru dodecahedra (d-Pt@Ru), are obtained to exhibit superior electrocatalytic activities for methanol oxidation. The optimal d-Pt@Ru dodecahedra present a mass activity of 0.80 A mgPt-1 and a specific activity of 1.61 mA cmPt-2, which are 5.25 and 7.78 times higher than those of the commercial Pt/C, respectively. Remarkably, both h-Pt@Ru and d-Pt@Ru show lower oxidation potentials and higher CO-poisoning resistance for methanol oxidation than PtRu nanoparticles (NPs) and commercial Pt/C. This is attributed to the hollow dodecahedron structures with optimal spatial elemental distributions, leading to high utilization of Pt at edges and corners and the exposure of abundant Pt-Ru interfaces. Our strategy offers a facile method to engineer bimetallic metal catalysts regardless of lattice mismatch.

Novel application of a Z-scheme photocatalyst of Ag3PO4@g-C3N4 for photocatalytic fuel cells.

A composite of Ag3PO4@g-C3N4 with the Z-scheme structure was synthesized, and used as the photoanode in a photocatalytic fuel cell (PFC). With the help of the Z-scheme design, both the degradation of tetracycline and the output of maximum power density (Pmax) were greatly enhanced in this PFC system. The degradation rate of tetracycline in the Ag3PO4@g-C3N4 PFC was 2.53 times and 3.65 times that in the PFC systems with the Ag3PO4 photoanode and the g-C3N4 photoanode, respectively. The Pmax of the Ag3PO4@g-C3N4 PFC was 6.06 µW cm-2, which was 1.46 times and 90.4 times that of the Ag3PO4 PFC (4.16 µW cm-2) and the g-C3N4 PFC (0.067 µW cm-2), respectively. The possible mechanism was proposed. The Z-scheme photoanode could not only contribute to the separation of photogenerated carriers to achieve a high photocatalytic activity, but also reserve a good redox capacity. Additionally, aeration played an important role on the PFC performance. It was demonstrated that N2 purging facilitated the electricity generation, while O2 purging promoted the pollutant degradation.

A model of molecular vector machine of proteins.

Based on the analysis of NiH⋯Oi-4C bond region of the proteins pentafragments using the quantum chemistry representations, a group of 20 vectors of action has been isolated. These vectors of action are reconstructed by a group of 20 side chains of amino acids being the irreducible representations of vectors. As a result, a model of molecular vector machine of proteins (MVM) has been proposed. This machine includes proteins pentafragments, a system of 20 vectors inside dodecahedron coming out of the Oi-4 atom as from the center and tetrahedral αi-carbon atom with the side chains of amino acids that change as the polypeptide chain grows. A model with the structured canonical set of amino acids based on the principles of antisymmetry was transferred onto the dodecahedron as an MVM element (Karasev et al., 2005; Karasev et al., 2007). The perspective of MVM application for predicting and designing the secondary structure of proteins has been discussed.

Nanoreactor Design Based on Self-Assembling Protein Nanocages.

Self-assembling proteins that form diverse architectures are widely used in material science and nanobiotechnology. One class belongs to protein nanocages, which are compartments with nanosized internal spaces. Because of the precise nanoscale structures, proteinaceous compartments are ideal materials for use as general platforms to create distinct microenvironments within confined cellular environments. This spatial organization strategy brings several advantages including the protection of catalyst cargo, faster turnover rates, and avoiding side reactions. Inspired by diverse molecular machines in nature, bioengineers have developed a variety of self-assembling supramolecular protein cages for use as biosynthetic nanoreactors that mimic natural systems. In this mini-review, we summarize current progress and ongoing efforts creating self-assembling protein based nanoreactors and their use in biocatalysis and synthetic biology. We also highlight the prospects for future research on these versatile nanomaterials.

Penton-dodecahedron of fowl adenovirus serotype 4 as a vaccine candidate for the control of related diseases.

In some serotypes of adenovirus (Ad), the penton base and attached trimeric fiber assemble into dodecameric virus-like particles called penton-dodecahedron (Pt-Dd), which can be internalized and used to deliver the vaccine antigens and drugs. Fowl adenovirus serotype 4 (FAdV-4) is an important pathogen, causing seriously economic loss to poultry industry in China and other counties. Pt-Dd particles from FAdV-4 infected cells, as well as in those infected with recombinant human Ad expressing fiber-1, fiber-2, and penton base of FAdV-4, were visualized by transmission electron microscopy. For the first time, we proved that FAdV-4 produced Pt-Dd in infected cells. Pt-Dd can also be assembled by the overexpressed recombinant proteins fiber-1, fiber-2, and penton base. Pt-Dd, as well as the recombinant proteins fiber-1, fiber-2, and penton base, were then used to immunize chickens. The humoral immune response, expression of selected immune molecules and challenge results were used to evaluate the immune efficacy of the vaccine candidates. Pt-Dd induced the highest level of enzyme-linked immunosorbent assay antibodies and significant high levels (p < 0.05) of interferonγ, interleukin-4, and major histocompatibility complex II expression in peripheral blood mononuclear cells at 48 h post-infection. The challenge results showed that Pt-Dd, inactivated FAdV-4 vaccine, and fiber-1 induced the best protection (100%), followed by fiber-2 (80%) and penton base (67%). The present study showed that FAdV-4 -Pt-Dd and recombinant fiber-1 are promising FAdV-4 vaccine candidates and could be used to replace the tissue-sourced inactivated FAdV-4 vaccine.

Correction of diffusion calculations when using two types of non-rectangular simulation boxes in molecular simulations.

Although simulation boxes used in molecular dynamics are normally chosen to be cubic or rectangular, two other cell shapes that are very familiar to crystallographers-the truncated octahedron and the rhombic dodecahedron-could also be used because they are also space-filling cells. Due to their spherical nature, these boxes have been intentionally applied in simulations of biomolecular solutions and liquid structures. Indeed, due to the advantages of running many molecular dynamic codes in parallel, simulations based on these non-rectangular boxes have been growing in popularity in recent years. In this work, the effects of using these two types of boxes on diffusion are explored for the first time, and an appropriate correction formula is derived theoretically within the framework of hydrodynamics. In addition, the range of validity for the correction formula is evaluated by performing molecular dynamic simulations on argon at three different densities.

Tuning Metallic Co0.85Se Quantum Dots/Carbon Hollow Polyhedrons with Tertiary Hierarchical Structure for High-Performance Potassium Ion Batteries.

Potassium-ion batteries (KIBs) are a potential candidate to lithium-ion batteries (LIBs) but possess unsatisfactory capacity and rate properties. Herein, the metallic cobalt selenide quantum dots (Co0.85Se-QDs) encapsulated in mesoporous carbon matrix were designed via a direct hydrothermal method. Specifically, the cobalt selenide/carbon composite (Co0.85Se-QDs/C) possesses tertiary hierarchical structure, which is the primary quantum dots, the secondary petals flake, and the tertiary hollow micropolyhedron framework. Co0.85Se-QDs are homogenously embedded into the carbon petals flake, which constitute the hollow polyhedral framework. This unique structure can take the advantages of both nanoscale and microscale features: Co0.85Se-QDs can expand in a multidimensional and ductile carbon matrix and reduce the K-intercalation stress in particle dimensions; the micropetals can restrain the agglomeration of active materials and promote the transportation of potassium ion and electron. In addition, the hollow carbon framework buffers volume expansion, maintains the structural integrity, and increases the electronic conductivity. Benefiting from this tertiary hierarchical structure, outstanding K-storage performance (402 mAh g-1 after 100 cycles at 50 mA g-1) is obtained when Co0.85Se-QDs/C is used as KIBs anode. More importantly, the selenization process in this work is newly reported and can be generally extended to prepare other quantum dots encapsulated in edge-limited frameworks for excellent energy storage.

Leukocytes and drug-resistant cancer cells are targets for intracellular delivery by adenoviral dodecahedron.

One of the major factors limiting the effectiveness of cancer chemotherapy is inefficient drug delivery. Systems enabling efficient delivery and enhanced intracellular uptake appear particularly promising in this respect. Virus-like particle, adenoviral dodecahedron (Dd), employs receptor-mediated endocytosis for cell penetration and is able to deliver intracellularly dozens of cargo molecules attached to one particle. We focused on studying Dd properties in the context of cancer treatment, showing that intratumoral injection of Dd, assessed in mouse xenograft model, results in vector accumulation in tumor without spreading in off-target organs. Moreover, we demonstrated that Dd is a promising vector targeting leukocytes and drug-resistant cancer cells. Dd uptake by human blood cells analyzed in vitro indicated the preference for leukocytes in comparison to red blood cells and platelets. Furthermore, internalization of Dd-doxorubicin conjugate by drug-resistant cells leads to increased nuclear accumulation of doxorubicin and significant enhancement of cytotoxicity against target cancer cells.