Endoscopic Submucosal Dissection Criteria for Differentiated-type Early Gastric Cancer Are Applicable to Mixed-type Differentiated Predominant.

BACKGROUND: There is a lack of sufficient evidence on whether mixed-type differentiated predominant early gastric cancer (MD-EGC) can be treated endoscopically by referring to the criteria for differentiated-type early gastric cancer (EGC). This study aims to evaluate the efficacy of endoscopic submucosal dissection (ESD) in MD-EGC. METHODS: Patients with differentiated-type EGC treated with ESD first from January 2015 to June 2021 were reviewed, including MD-EGC and pure differentiated-type EGC (PD-EGC). Clinical data, including the clinicopathological characteristics, resection outcomes of ESD, and recurrence and survival time, were collected, and the difference between MD-EGC and PD-EGC was tested. RESULTS: A total of 48 patients (48 lesions) with MD-EGC and 850 patients (890 lesions) with PD-EGC were included. Compared with PD-EGC, MD-EGC had a higher submucosal invasion rate (37.5% vs. 13.7%, P<0.001) and lymphatic invasion rate (10.4% vs. 0.4%, P<0.001). The rates of complete resection (70.8% vs. 92.5%, P<0.001) and curative resection (54.2% vs. 87.4%, P<0.001) in MD-EGC were lower than those of PD-EGC. Multivariate analysis revealed that MD-EGC (OR 4.26, 95% CI, 2.22-8.17, P<0.001) was an independent risk factor for noncurative resection. However, when curative resection was achieved, there was no significant difference in the rates of recurrence (P=0.424) between the 2 groups, whether local or metachronous recurrence. Similarly, the rates of survival(P=0.168) were no significant difference. CONCLUSIONS: Despite the greater malignancy and lower endoscopic curative resection rate of MD-EGC, patients who met curative resection had a favorable long-term prognosis.

Ten-Day Vonoprazan-Amoxicillin Dual Therapy as a First-Line Treatment of Helicobacter pylori Infection Compared With Bismuth-Containing Quadruple Therapy.

INTRODUCTION: No study has investigated the efficacy and safety of vonoprazan-amoxicillin dual therapy compared with bismuth quadruple therapy (B-quadruple). This study aimed to evaluate the efficacy and safety of 10-day vonoprazan-amoxicillin dual therapy as a first-line treatment of Helicobacter pylori infection compared with B-quadruple and to explore the optimal dosage of amoxicillin in the dual therapy. METHODS: A total of 375 treatment-naive, H. pylori -infected subjects were randomly assigned in a 1:1:1 ratio into 3 regimen groups including VHA-dual (vonoprazan 20 mg twice/day + amoxicillin 750 mg 4 times/day), VA-dual (vonoprazan 20 mg + amoxicillin 1,000 mg twice/day), and B-quadruple (esomeprazole 20 mg + bismuth 200 mg + amoxicillin 1,000 mg + clarithromycin 500 mg twice/day). Eradication rates, adverse events (AEs), and compliance were compared between 3 groups. RESULTS: The eradication rates of B-quadruple, VHA-dual, and VA-dual were 90.9%, 93.4%, and 85.1%, respectively, by per-protocol analysis; 89.4%, 92.7%, and 84.4%, respectively, by modified intention-to-treat analysis; 88.0%, 91.2%, and 82.4%, respectively, by intention-to-treat analysis. The efficacy of the VHA-dual group was not inferior to the B-quadruple group ( P < 0.001), but VA-dual did not reach a noninferiority margin of -10%. The AEs rates of the B-quadruple group were significantly higher than those of the VHA-dual ( P = 0.012) and VA-dual ( P = 0.001) groups. There was no significant difference in medication compliance among 3 treatment groups ( P = 0.995). CONCLUSIONS: The 10-day VHA-dual therapy provided satisfactory eradication rates of >90%, lower AEs rates, and similar adherence compared with B-quadruple therapy as a first-line therapy for H. pylori infection. However, the efficacy of VA-dual therapy was not acceptable.

Highly Active Zinc Sulfide Composite Microspheres: A Versatile Template for Synthesis of a Family of Hollow Nanostructures of Sulfides.

Hollow nanostructures of metal sulfides have gained tremendous attention in catalysis, biomedicine, and energy storage and conversion owing to their intriguing structural features and fascinating physicochemical properties. Here, we reported a hard template-engaged cation exchange method to fabricate a family of binary or ternary metal sulfide (CuS, Ag2S, Bi2S3, CuxBi1-xS, ZnxCo1-xS, ZnxCd1-xS, ZnxNi1-xS, and ZnxMn1-xS) hollow microspheres via adjusting the reaction kinetic parameters including solvent and temperature in the presence of unique ZnS composite microspheres. Particularly, the shell layer thickness of metal sulfide hollow microspheres could be modulated by manipulating the reaction temperature during the cation exchanging procedure. Meanwhile, the desired elementary composition of ternary metal sulfide hollow microspheres could be achieved by varying the mole ratio and species of the metal source. This synthetic strategy could be extended to rationally design and construct other metal sulfide hollow nanostructures and provide a deep insight into the nucleation and growth process of the metal sulfide hollow microspheres with well-controlled composition and microstructures.

Recent Development on Controlled Synthesis of Metal Sulfides Hollow Nanostructures via Hard Template Engaged Strategy: A Mini-Review.

In this mini-review, we highlighted the recent progresses in the controlled synthesis of metal sulfides hollow nanostructures via hard template technique. After a brief introduction about the formation mechanism of the inorganic hollow nanostructures via hard template technique, the discussions primarily focused on the emerging development of metal sulfides hollow nanostructures. Various synthetic strategies were summarized concerning the use of the hard template engaged strategies to fabricate various metal sulfides hollow nanostructures, such as hydrothermal method, solvothermal method, ion-exchange, sulfidation or calcination etc. Finally, the perspectives and summaries have been presented to demonstrate that a facile synthetic technique would be widely used to fabricate metal sulfides hollow nanostructures with multi-shells and components.

Autophagic blockage by bismuth sulfide nanoparticles inhibits migration and invasion of HepG2 cells.

The biological effects of nanoparticles are of great importance for the in-depth understanding of safety issues in biomedical applications. Induction of autophagy is a cellular response after nanoparticle exposure. Bismuth sulfide nanoparticles (Bi2S3 NPs) are often used as a CT contrast agent because of their excellent photoelectric conversion ability. Yet there has been no previous detailed study other than a cell toxicity assessment. In this study, three types of Bi2S3 NPs with different shapes (Bi2S3 nano rods (BSNR), hollow microsphere Bi2S3 NPs (BSHS) and urchin-like hollow microsphere Bi2S3 NPs (ULBSHS)) were used to evaluatecytotoxicity, autophagy induction, cell migration and invasion in human hepatocellular carcinoma cells (HepG2). Results showed that all three Bi2S3 NPs lead to blockage in autophagic flux, causing p62 protein accumulation. The cell death caused by these Bi2S3 NPs is proved to be autophagy related, rather than related to apoptosis. Moreover, Bi2S3 NPs can reduce the migration and invasion in HepG2 cells in an autophagy-dependent manner. ULBSHS is the most cytotoxic among three Bi2S3 NPs and has the best tumor metastasis suppression. These results demonstrated that, even with relatively low toxicity of Bi2S3 NPs, autophagy blockage may still substantially influence cell fate and thus significantly impact their biomedical applications, and that surface topography is a key factor regulating their biological response.

Sequential Growth of High Quality Sub-10 nm Core-Shell Nanocrystals: Understanding the Nucleation and Growth Process Using Dynamic Light Scattering.

Monodisperse sub-10 nm core-shell nanocrystals have been extensively studied owing to their important applications in catalysis, bioimaging, nanomedicine, and so on. In this work, an amorphous shell component crystallization strategy has been proposed to prepare high quality sub-10 nm NaYF4:Yb/Er@NaGdF4 core-shell nanocrystals successfully via a sequential growth process. The dynamic light scattering technique has been used to investigate the secondary nucleation and growth process forming the core-shell nanocrystals. The size and morphology evolution of the core-shell nanocrystals reveals that the secondary nucleation of the shell component is unavoidable after hot-injecting the shell precursor at high temperatures, which was followed by dissolution and recrystallization (an Ostwald ripening process) to partially produce the core-shell nanocrystals. The present study demonstrates that the size of seed nanocrystals and the injection temperature of the shell component precursor play a vital role in the formation of core-shell nanostructures completely. This work will provide an alternative strategy for precisely controlling the fabrication of sub-10 nm core-shell nanostructures for various applications.

Magnetically Recyclable Fe3O4@Zn xCd1- xS Core-Shell Microspheres for Visible Light-Mediated Photocatalysis.

Magnetically recyclable photocatalyst has drawn considerable research interest because of its importance in practical applications. Herein, we demonstrate a facile hydrothermal process to fabricate magnetic core-shell microspheres of Fe3O4@Zn xCd1- xS, successfully using Fe3O4@ZnS core-shell microspheres as sacrificed templates. The as-prepared magnetically recyclable photocatalysts show efficient photochemical reduction of Cr(VI) under irradiation of visible light. The photochemical reduction mechanism has been studied to illustrate the reduction-oxidation ability of the photogenerated electrons (e-) and holes (h+), which play an important role in the reduction of Cr(VI) to Cr(III) and oxidation of organic dyes. The as-prepared Fe3O4@Zn0.55Cd0.45S core-shell microspheres show good chemical stability and only a slight decrease in the photocatalytic activity after four recycles. In particular, the as-prepared photocatalysts could be easily recycled and reused by an external magnetic field. Therefore, this work would provide a facile chemical approach for controlled synthesis of magnetic nanostructures combined with alloyed semiconductor photocatalysts for wastewater treatment.

Large-Scale Synthesis of Highly Luminescent Perovskite-Related CsPb2 Br5 Nanoplatelets and Their Fast Anion Exchange.

All-inorganic cesium lead-halide perovskite nanocrystals have emerged as attractive optoelectronic nanomaterials owing to their stabilities and highly efficient photoluminescence. Herein we report a new type of highly luminescent perovskite-related CsPb2 Br5 nanoplatelets synthesized by a facile precipitation reaction. The layered crystal structure of CsPb2 Br5 promoted an anisotropic two-dimensional (2D) crystal growth during the precipitation process, thus enabling the large-scale synthesis of CsPb2 Br5 nanoplatelets. Fast anion exchange has also been demonstrated in as-synthesized CsPb2 Br5 nanoplatelets to extend their photoluminescence spectra to the entire visible spectral region. The large-scale synthesis and optical tunability of CsPb2 Br5 nanoplatelets will be advantageous in future applications of optoelectronic devices.

Multiplex templating process in one-dimensional nanoscale: controllable synthesis, macroscopic assemblies, and applications.

Since their detection 20 years ago, carbon nanotubes (CNTs) have captured the interest of scientists, because one-dimensional (1D) nanostructures (nanowires, nanotubes, and nanoribbons) have fascinating physical properties and many potential technological applications. These are materials with structural features limited to the range of 1-100 nm in one dimension, and unlimited in the others. When their size goes down to certain characteristic lengths, such as the Bohr radius, the wavelength of incandescent light, and the phonon mean-free path, quantum mechanical effects can occur. This results in novel optical, magnetic, and electronic characteristics. These physical properties, along with unique transport features in the longitudinal direction and large surface-to-volume ratio, make 1D nanostructures attract extensive attention in both fundamental research and engineering applications. From a synthetic point of view, it is highly desirable to develop a simple route for fabricating 1D nanostructures in large scale at low cost. On the other hand, in order to transfer the intrinsic features of individual 1D nanostructures into macroscopic scale and realize practical applications, we need to explore highly efficient and scalable assembly methods to integrate 1D nanostructures into functional macroscopic architectures. In 2006, our group developed a simple hydrothermal method for synthesizing ultrathin Te nanowires (TeNWs) using conventional chemicals. As we found through systematic study over the past several years, we can use the ultrathin TeNWs as a versatile templating material to fabricate a series of high-quality 1D nanostructures by taking the unique advantages of TeNWs, such as large-scale synthesis, high processability, and high reactivity. The obtained 1D products inherit the dimensional (high aspect ratio) and mechanical (high flexibility) features of the original TeNW templates, thus allowing us to construct macroscopic architectures by using them as nanoscale building blocks. In this Account, we describe on our recent developments in the multiplex templating synthesis of 1D nanostructures, their macroscopic assemblies, and applications. We first introduce ultrathin TeNWs and their advantages as a templating material. Through the multiplex templating process, we can prepare a family of 1D nanostructures that covers a wide range of materials, including noble metals, metal oxides, semiconductors, carbon, polymers, and their binary and multiple hybrids. We emphasize the reactivity of templating materials and the versatility of templating processes in this Account. On the basis of the templated 1D products, we then describe a series of macroscopic assemblies of 1D nanostructures, including free-standing membranes, films, hydrogels, and aerogels. These exhibit enormous potential for attractive applications, such as liquid filtration and separation, continuous-flow catalysis, electrocatalysis, polymer-based nanocomposites, and superadsorbents, and elastomeric conductors. We believe that the great versatility of templating synthesis, a scalable assembling process, and large-scale synthesis can significantly enhance the application reliability of the 1D nanostructures.

Nanoscale coordination polymer Fe-DMY downregulating Poldip2-Nox4-H2O2 pathway and alleviating diabetic retinopathy.

Diabetic retinopathy (DR) is a prevalent microvascular complication of diabetes and the leading cause of blindness and severe visual impairment in adults. The high levels of glucose trigger multiple intracellular oxidative stress pathways, such as POLDIP2, resulting in excessive reactive oxygen species (ROS) production and increased expression of vascular cell adhesion molecule-1 (VCAM-1), hypoxia-inducible factor 1α (HIF-1α), and vascular endothelial growth factor (VEGF), causing microvascular dysfunction. Dihydromyricetin (DMY) is a natural flavonoid small molecule antioxidant. However, it exhibits poor solubility in physiological environments, has a short half-life in vivo, and has low oral bioavailability. In this study, we present, for the first time, the synthesis of ultra-small Fe-DMY nano-coordinated polymer particles (Fe-DMY NCPs), formed by combining DMY with low-toxicity iron ions. In vitro and in vivo experiments confirm that Fe-DMY NCPs alleviate oxidative stress-induced damage to vascular endothelial cells by high glucose, scavenge excess ROS, and improve pathological features of DR, such as retinal vascular leakage and neovascularization. Mechanistic validation indicates that Fe-DMY NCPs can inhibit the activation of the Poldip2-Nox4-H2O2 signaling pathway and downregulate vital vascular function indicators such as VCAM-1, HIF-1α, and VEGF. These findings suggest that Fe-DMY NCPs could serve as a safe and effective antioxidant and microangio-protective agent, with the potential as a novel multimeric drug for DR therapy.

Nanosensitizers for sonodynamic therapy for glioblastoma multiforme: current progress and future perspectives.

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor, and it is associated with poor prognosis. Its characteristics of being highly invasive and undergoing heterogeneous genetic mutation, as well as the presence of the blood-brain barrier (BBB), have reduced the efficacy of GBM treatment. The emergence of a novel therapeutic method, namely, sonodynamic therapy (SDT), provides a promising strategy for eradicating tumors via activated sonosensitizers coupled with low-intensity ultrasound. SDT can provide tumor killing effects for deep-seated tumors, such as brain tumors. However, conventional sonosensitizers cannot effectively reach the tumor region and kill additional tumor cells, especially brain tumor cells. Efforts should be made to develop a method to help therapeutic agents pass through the BBB and accumulate in brain tumors. With the development of novel multifunctional nanosensitizers and newly emerging combination strategies, the killing ability and selectivity of SDT have greatly improved and are accompanied with fewer side effects. In this review, we systematically summarize the findings of previous studies on SDT for GBM, with a focus on recent developments and promising directions for future research.

Mesoporous-silica-coated up-conversion fluorescent nanoparticles for photodynamic therapy.

Near-infrared (NIR)-to-visible up-conversion fluorescent nanoparticles have potential to be used for photodynamic therapy (PDT) in deep tissue because NIR light can penetrate thick tissue due to weak absorption in the optical window. Here a uniform layer of mesoporous silica is coated onto NaYF(4) up-converting nanocrystals, with a large surface area of approximately 770 m(2) g(-1) and an average pore size of 2 nm. A photosensitizer, zinc phthalocyanine, is incorporated into the mesoporous silica. Upon excitation by a NIR laser, the nanocrystals convert NIR light to visible light, which further activates the photosensitizer to release reactive singlet oxygen to kill cancer cells. The photosensitizer encapsulated in mesoporous silica is protected from degradation in the harsh biological environment. It is demonstrated that the photosensitizers loaded into the porous silica shell of the nanoparticles are not released out of the silica while they continuously produce singlet oxygen upon excitation by a NIR laser. The nanoparticles are reusable as the photosensitizers encapsulated in the silica are removed by soaking in ethanol.

Epitaxial growth of ultrathin layers on the surface of sub-10 nm nanoparticles: the case of ß-NaGdF4:Yb/Er@NaDyF4 nanoparticles.

Upconversion core-shell nanoparticles have attracted a large amount of attention due to their multifunctionality and specific applications. In this work, based on a NaGdF4 sub-10 nm ultrasmall nanocore, a series of core-shell upconversion nanoparticles with uniform size doped with Yb3+, Er3+ and NaDyF4 shells with different thicknesses were synthesized by a facile sequential growth process. NaDyF4 coated upconversion luminescent nanoparticles showed an obvious fluorescence quenching under excitation at 980 nm as a result of energy resonance transfer between Yb3+, Er3+ and Dy3+. NaGdF4:Yb,Er@NaDyF4 core-shell nanoparticles with ultrathin layer shells exhibited a better T 1-weighted MR contrast.

Controlled synthesis of upconverting nanoparticles/CuS yolk-shell nanoparticles for in vitro synergistic photothermal and photodynamic therapy of cancer cells.

Synergistic photodynamic and photothermal therapy of cancer cells is of considerable scientific and technological interest. In this work, we demonstrate a sacrificial template strategy to fabricate yolk-shell nanoparticles combining upconversion nanoparticles (UCNPs) and CuS nanoparticles. Lanthanide-doped upconversion nanoparticles of NaYF4:30% Yb,1% Nd,0.5% Er@NaYF4:20% Nd (also denoted as UCNPs) have been prepared as 808 nm light excited remote-controlled nanotransducers for in vitro cancer cell treatment. The upconversion fluorescence of the as-prepared UCNPs@CuS yolk-shell nanoparticles is completely quenched under the excitation of an 808 nm laser, which demonstrates that the energy transfer between the UCNPs and CuS is very efficient. In addition, the as-prepared UCNPs@CuS nanoparticles show higher production ability for hydroxyl radicals (˙OH) and singlet oxygen (1O2) compared to CuS hollow nanospheres of similar size. In particular, the excited shell layer (CuS) showed an enhanced photothermal effect while producing reactive oxygen species (ROS) including singlet oxygen (1O2) and hydroxyl radicals (˙OH) after being exposed to near infrared (NIR) light. Thus, the as-prepared UCNPs@CuS yolk-shell nanoparticles exhibited the synergistic effect of photothermal and photodynamic therapy of cancer cells, which resulted in significant cell death after exposure to an 808 nm laser. The synthetic strategy will provide an alternative method to fabricate other UCNP based core-shell nanoparticles for potential and important applications in bionanotechnology including theranostics, multimodal treatment, magnetic resonance imaging-guided photodynamic therapy, etc.

Sequential Growth of NaYF4:Yb/Er@NaGdF4 Nanodumbbells for Dual-Modality Fluorescence and Magnetic Resonance Imaging.

Upconversional core-shell nanostructures have gained considerable attention due to their distinct enhanced fluorescence efficiency, multifunctionality, and specific applications. Recently, we have developed a sequential growth process to fabricate unique upconversion core-shell nanoparticles. Time evolution of morphology for the NaYF4:Yb/Er@NaGdF4 nanodumbbells has been extensively investigated. An Ostwald ripening growth mechanism has been proposed to illustrate the formation of NaYF4:Yb/Er@NaGdF4 nanodumbbells. The hydrophilic NaYF4:Yb/Er@NaGdF4 core-shell nanodumbbells exhibited strong upconversion fluorescence and showed higher magnetic resonance longitudinal relaxivity (r1 = 7.81 mM-1 s-1) than commercial contrast agents (Gd-DTPA). NaYF4:Yb/Er@NaGdF4 nanodumbbells can serve as good candidates for high efficiency fluorescence and magnetic resonance imaging.

Sequential growth of CaF2:Yb,Er@CaF2:Gd nanoparticles for efficient magnetic resonance angiography and tumor diagnosis.

It is a significant challenge to develop nanoscale magnetic resonance imaging (MRI) contrast agents with high performance of relaxation. In this work, Gd3+-doped CaF2-based core-shell nanoparticles (CaF2:Yb,Er@CaF2:Gd) of sub-10 nm size were controllably synthesized by a facile sequential growth method. The as-prepared hydrophilic CaF2:Yb,Er@CaF2:Gd nanoparticles modified using PEG-PAA di-block copolymer benefited from the presence of Gd only in the outer CaF2 layer of the nanoparticles, which exhibited r1 as high as 21.86 mM-1 s-1 under 3.0 T, seven times as high as that of commercially used gadopentetate dimeglumine (Gd-DTPA). Low cytotoxicity, no hemolysis phenomenon and no potential gadolinium ion leakage phenomenon of the hydrophilic CaF2:Yb,Er@CaF2:Gd nanoparticles have been observed and confirmed. Clear vascular details can be observed in magnetic resonance angiography and obvious MR signal of 4T1 tumor area could be significantly improved by intravenous injection of the hydrophilic CaF2:Yb,Er@CaF2:Gd nanoparticles at a low dosage in mice. A series of in vivo biological safety evaluations confirmed the good biocompatibility of the hydrophilic CaF2:Yb,Er@CaF2:Gd nanoparticles, which might be employed in clinical blood pool imaging and tumor diagnosis as a safe and efficient MRI probe.

Large scale synthesis of uniform silver@carbon rich composite (carbon and cross-linked PVA) sub-microcables by a facile green chemistry carbonization approach.

A facile green chemistry carbonization method has been discovered for the synthesis of uniform silver@carbon rich composite (carbon and cross-linked polyvinyl alcohol) core-shell sub-microcables in large quantities, where the carbon sources such as glucose-based saccharides have played important roles in the formation of these novel sub-microcables.

Titanium Dioxide/Upconversion Nanoparticles/Cadmium Sulfide Nanofibers Enable Enhanced Full-Spectrum Absorption for Superior Solar Light Driven Photocatalysis.

In this work, we demonstrate an electrospinning technique to fabricate TiO2 /upconversion nanoparticles (UCNPs)/CdS nanofibers on large scale. In addition, the as-prepared TiO2 nanofibers are incorporated with a high population of UCNPs and CdS nanospheres; this results in Förster resonance energy-transfer configurations of the UCNPs, TiO2 , and CdS nanospheres that are in close proximity. Hence, strong fluorescent emissions for the Tm(3+) ions including the (1) G4 →(3) H6 transition are efficiently transferred to TiO2 and the CdS nanoparticles through an energy-transfer process. The as-prepared TiO2 /UCNPs/CdS nanofibers exhibit full-spectrum solar-energy absorption and enable the efficient degradation of organic dyes by fluorescence resonance energy transfer between the UCNPs and TiO2 (or CdS). The UCNPs/TiO2 /CdS nanofibers may also have enhanced energy-transfer efficiency for wide applications in solar cells, bioimaging, photodynamics, and chemotherapy.

A Donor-Acceptor Conjugated Polymer with Alternating Isoindigo Derivative and Bithiophene Units for Near-Infrared Modulated Cancer Thermo-Chemotherapy.

Conjugated polymers containing alternating donor/acceptor units have strong and sharp absorbance peaks in near-infrared (NIR) region, which could be suitable for photothermal therapy. However, these polymers as photothermal transducers are rarely reported because of their water insolubility, which limits their applications for cancer therapy. Herein, we report the donor-acceptor conjugated polymer PBIBDF-BT with alternating isoindigo derivative (BIBDF) and bithiophene (BT) units as a novel photothermal transducer, which exhibited strong near-infrared (NIR) absorbance due to its low band gap (1.52 eV). To stabilize the conjugated polymer physiological environments, we utilized an amphiphilic copolymer, poly(ethylene glycol)-block-poly(hexyl ethylene phosphate) (mPEG-b-PHEP), to stabilize PBIBDF-BT-based nanoparticles (PBIBDF-BT@NPPPE) through a single emulsion method. The obtained nanoparticles PBIBDF-BT@NPPPE showed great stability in physiological environments and excellent photostability. Moreover, the PBIBDF-BT@NPPPE exhibited high photothermal conversion efficiency, reaching 46.7%, which is relatively high compared with those of commonly used materials for photothermal therapy. Accordingly, in vivo and in vitro experiments demonstrated that PBIBDF-BT@NPPPE exhibits efficient photothermal anticancer efficacy. More importantly, PBIBDF-BT@NPPPE could simultaneously encapsulate other types of therapeutic agents though hydrophobic interactions with the PHEP core and achieve NIR-triggered intracellular drug release and a synergistic combination therapy of thermo-chemotherapy for the treatment of cancer.

Redox-Responsive Polyphosphoester-Based Micellar Nanomedicines for Overriding Chemoresistance in Breast Cancer Cells.

Multidrug resistance (MDR) has been recognized as a key factor contributing to the failure of chemotherapy for cancer in the clinic, often due to insufficient delivery of anticancer drugs to target cells. For addressing this issue, a redox-responsive polyphosphoester-based micellar nanomedicine, which can be triggered to release transported drugs in tumor cells, has been developed. The micelles are composed of diblock copolymers with a hydrophilic PEG block and a hydrophobic polyphosphoester (PPE) block bearing a disulfide bond in a side group. After incubating the redox-responsive micelles with drug-resistant tumor cells, the intracellular accumulation and retention of DOX were significantly enhanced. Moreover, after internalization by MDR cancer cells, the disulfide bond in the side group was cleaved by the high intracellular glutathione levels, resulting in a hydrophobic to hydrophilic transition of the PPE block and subsequent disassembly of the micelles. Thus, the encapsulated DOX was rapidly released, and abrogation of drug resistance in the cancer cells was observed in vitro. Moreover, the DOX-loaded redox-responsive micelles exhibited significantly enhanced inhibition of tumor growth in nude mice bearing MCF-7/ADR xenograft tumors via tail vein injection, indicating that such micelles have great potential in overcoming MDR for cancer therapy.