ALD-induced TiO2/Ag nanofilm for rapid surface photodynamic ion sterilization.

The daily life of people in the intelligent age is inseparable from electronic device, and a number of bacteria on touch screens are increasingly threatening the health of users. Herein, a photocatalytic TiO2/Ag thin film was synthesized on a glass by atomic layer deposition and subsequent in situ reduction. Ultraviolet-visible (UV-Vis) spectra showed that this film can harvest the simulated solar light more efficiently than that of pristine TiO2. The antibacterial tests in vitro showed that the antibacterial efficiency of the TiO2/Ag film against S. aureus and E. coli was 98.2% and 98.6%, under visible light irradiation for 5 min. The underlying mechanism was that the in-situ reduction of Ag on the surface of TiO2 reduced the bandgap of TiO2 from 3.44 to 2.61 eV due to the formation of Schottky heterojunction at the interface between TiO2 and Ag. Thus, TiO2/Ag can generate more reactive oxygen species for bacterial inactivation on the surface of electronic screens. More importantly, the TiO2/Ag film had great biocompatibility with/without light irradiation. The platform not only provides a more convenient choice for the traditional antibacterial mode but also has limitless possibilities for application in the field of billions of touch screens.

Rhodium(I) Complex-Based Polymeric Nanomicelles in Water Exhibiting Coexistent Near-Infrared Phosphorescence Imaging and Anticancer Activity in Vivo.

Metal complexes that exhibit both near-infrared (NIR) phosphorescence imaging and chemotherapeutic activity would represent a novel class of anticancer drugs in clinical tumor treatment. In this work, a series of novel rodlike nanomicelles have been fabricated in water by coupling poly(ethylene oxide)-block-poly(sodium acrylate) and [Rh(C≡N-2,6-xylyl)4]+(1/2SO4)-. These nanomicelles exhibit intense NIR phosphorescence and excellent stability. As revealed by in vivo NIR phosphorescence imaging data, the rodlike nanomicelle can selectively stain tumor sites with a long retention time. Moreover, the nanorods demonstrate effective anticancer activity by precisely killing tumor tissues without damaging healthy organs in vivo. To the best of our knowledge, this research provides the first example of metal-based complexes showing simultaneous NIR luminescence imaging and antitumor activity in vivo.

Functional Nanocomplexes with Vascular Endothelial Growth Factor A/C Isoforms Improve Collateral Circulation and Cardiac Function.

Protein-based therapies are potential treatments for cancer, immunological, and cardiovascular diseases. However, effective delivery systems are needed because of their instability, immunogenicity, and so on. Crosslinked negatively charged heparin polysaccharide nanoparticle (HepNP) is proposed for protein delivery. HepNP can efficiently condense vascular endothelial growth factor (VEGF) because of the unique electronegative sulfonic acid and carboxyl domain of heparin. HepNP is then assembled with VEGF-C (Hep@VEGF-C) or VEGF-A (Hep@VEGF-A) protein for the therapy of myocardial infarction (MI) via intravenous (iv) injection. Hep@VEGF-A-mediated improvement of cardiac function by promoting angiogenesis is limited because of elevated vascular permeability, while Hep@VEGF-C effectively promotes lymphangiogenesis and reduces edema. On this basis, a graded delivery of VEGF-C (0.5-1 h post-MI) and VEGF-A (5 d post-MI) using HepNP is developed. At the dose ratio of 3:1 (Hep@VEGF-C vs Hep@VEGF-A), Hep@VEGF functional complexes substantially reduce the scar formation (≈-39%; p < 0.05) and improve cardiac function (≈+74%; p < 0.05). Such a HepNP delivery system provides a simple and effective therapeutic strategy for cardiovascular diseases by delivering functional proteins. Because of the unique binding ability of heparin with cytokines and growth factors, HepNP also has considerable application prospects in protein therapy for other serious diseases.

Three-Pronged Attack by Homologous Far-red/NIR AIEgens to Achieve 1+1+1>3 Synergistic Enhanced Photodynamic Therapy.

Photodynamic therapy (PDT) has long been shown to be a powerful therapeutic modality for cancer. However, PDT is undiversified and has become stereotyped in recent years. Exploration of distinctive PDT methods is thus highly in demand but remains a severe challenge. Herein, an unprecedented 1+1+1>3 synergistic strategy is proposed and validated for the first time. Three homologous luminogens with aggregation-induced emission (AIE) characteristics were rationally designed based on a simple backbone. Through slight structural tuning, these far-red/near-infrared AIE luminogens are capable of specifically anchoring to mitochondria, cell membrane, and lysosome, and effectively generating reactive oxygen species (ROS). Notably, biological studies demonstrated combined usage of three AIE photosensitizers gives multiple ROS sources simultaneously derived from several organelles, which gives superior therapeutic effect than that from a single organelle at the same photosensitizers concentration. This strategy is conceptually and operationally simple, providing an innovative approach and renewed awareness of improving therapeutic effect through three-pronged PDT.

Oxidation-Responsive Nanoassemblies for Light-Enhanced Gene Therapy.

Microenvironment-responsive supramolecular assemblies have attracted great interest in the biomedical field due to their potential applications in controlled drug release. In this study, oxidation-responsive supramolecular polycationic assemblies named CPAs are prepared for nucleic acid delivery via the host-guest interaction of ß-cyclodextrin based polycations and a ferrocene-functionalized zinc tetraaminophthalocyanine core. The reactive oxygen species (ROS) can accelerate the disassembly of CPA/pDNA complexes, which would facilitate the release of pDNA in the complexes and further benefit the subsequent transfection. Such improvement in transfection efficiency is proved in A549 cells with high H2 O2 concentration. Interestingly, the transfection efficiencies mediated by CPAs are also different in the presence or absence of light in various cell lines such as HEK 293 and 4T1. The single oxygen (1 O2 ), produced by photosensitizers in the core of CPAs under light, increases the ROS amount and accelerates the disassembly of CPAs/pDNA complexes. In vitro and in vivo studies further illustrate that suppressor tumor gene p53 delivered by CPAs exhibits great antitumor effects under illumination. This work provides a promising strategy for the design and fabrication of oxidation-responsive nanoassemblies with light-enhanced gene transfection performance.

The research status and prospects of nanomaterials in wound healing: A scientometric study.

Nanotechnology and nanomaterials have swiftly influenced wound healing, propelling the development of wound-healing nanomaterials. Therefore, it's crucial to gather essential information about prominent researches in this domain. Moreover, identifying primary directions and related frontiers in wound healing and nanomaterials is paramount. This will enhance our comprehension of the current research landscape and foster progress in this field. Retrieved from the Web of Science core database, a total of 838 relevant studies published from 2013 to 2022 were analyzed through bibliometric visualization tools such as CiteSpace, VOSviewer, and Bibliometrics Online Analysis Platform. The annual study count has been rising steadily, primary contributors to this field include China, India, and the United States. The author with the highest output is Zangeneh, Akram, while Grumezescu, Alexandru Mihai garners the most citations. Chinese Academy of Sciences emerges as the leading institution, with Nanomaterials as the predominant journal. The keyword "antibacterial" signals prevailing and forthcoming trends in this domain. This study presents the first scientometric study and bibliometric visualization for wound healing-related nanomaterials, shedding light on research hotspots and trends. Over the course of the decade from 2013 to 2022, enthusiasm for nanomaterials in wound healing research has surged, auguring well for upcoming investigations.

Microgel-based carriers enhance skeletal stem cell reprogramming towards immunomodulatory phenotype in osteoarthritic therapy.

Skeletal stem cells (SSC) have gained attentions as candidates for the treatment of osteoarthritis due to their osteochondrogenic capacity. However, the immunomodulatory properties of SSC, especially under delivery operations, have been largely ignored. In the study, we found that Pdpn+ and Grem1+ SSC subpopulations owned immunoregulatory potential, and the single-cell RNA sequencing (scRNA-seq) data suggested that the mechanical activation of microgel carriers on SSC induced the generation of Pdpn+Grem1+Ptgs2+ SSC subpopulation, which was potent at suppressing macrophage inflammation. The microgel carriers promoted the YAP nuclear translocation, and the activated YAP protein was necessary for the increased expression of Ptgs2 and PGE2 in microgels-delivered SSC, which further suppressed the expression of TNF-ɑ, IL-1ß and promoted the expression of IL-10 in macrophages. SSC delivered with microgels yielded better preventive effects on articular lesions and macrophage activation in osteoarthritic rats than SSC without microgels. Chemically blocking the YAP and Ptgs2 in microgels-delivered SSC partially abolished the enhanced protection on articular tissues and suppression on osteoarthritic macrophages. Moreover, microgel carriers significantly prolonged SSC retention time in vivo without increasing SSC implanting into osteoarthritic joints. Together, our study demonstrated that microgel carriers enhanced SSC reprogramming towards immunomodulatory phenotype to regulate macrophage phenotype transformation for effectively osteoarthritic therapy by promoting YAP protein translocation into nucleus. The study not only complement and perfect the immunological mechanisms of SSC-based therapy at the single-cell level, but also provide new insight for microgel carriers in stem cell-based therapy.

Piezo-enhanced near infrared photocatalytic nanoheterojunction integrated injectable biopolymer hydrogel for anti-osteosarcoma and osteogenesis combination therapy.

Preventing local tumor recurrence while promoting bone tissue regeneration is an urgent need for osteosarcoma treatment. However, the therapeutic efficacy of traditional photosensitizers is limited, and they lack the ability to regenerate bone. Here, a piezo-photo nanoheterostructure is developed based on ultrasmall bismuth/strontium titanate nanocubes (denoted as Bi/SrTiO3), which achieve piezoelectric field-driven fast charge separation coupling with surface plasmon resonance to efficiently generate reactive oxygen species. These hybrid nanotherapeutics are integrated into injectable biopolymer hydrogels, which exhibit outstanding anticancer effects under the combined irradiation of NIR and ultrasound. In vivo studies using patient-derived xenograft models and tibial osteosarcoma models demonstrate that the hydrogels achieve tumor suppression with efficacy rates of 98.6 % and 67.6 % in the respective models. Furthermore, the hydrogel had good filling and retention capabilities in the bone defect region, which exerted bone repair therapeutic efficacy by polarizing and conveying electrical stimuli to the cells under mild ultrasound radiation. This study provides a comprehensive and clinically feasible strategy for the overall treatment and tissue regeneration of osteosarcoma.

Enhanced pyroptosis induction with pore-forming gene delivery for osteosarcoma microenvironment reshaping.

Osteosarcoma is the most common malignant bone tumor without efficient management for improving 5-year event-free survival. Immunotherapy is also limited due to its highly immunosuppressive tumor microenvironment (TME). Pore-forming gasdermins (GSDMs)-mediated pyroptosis has gained increasing concern in reshaping TME, however, the expressions and relationships of GSDMs with osteosarcoma remain unclear. Herein, gasdermin E (GSDME) expression is found to be positively correlated with the prognosis and immune infiltration of osteosarcoma patients, and low GSDME expression was observed. A vector termed as LPAD contains abundant hydroxyl groups for hydrating layer formation was then prepared to deliver the GSDME gene to upregulate protein expression in osteosarcoma for efficient TME reshaping via enhanced pyroptosis induction. Atomistic molecular dynamics simulations analysis proved that the hydroxyl groups increased LPAD hydration abilities by enhancing coulombic interaction. The upregulated GSDME expression together with cleaved caspase-3 provided impressive pyroptosis induction. The pyroptosis further initiated proinflammatory cytokines release, increased immune cell infiltration, activated adaptive immune responses and create a favorable immunogenic hot TME. The study not only confirms the role of GSDME in the immune infiltration and prognosis of osteosarcoma, but also provides a promising strategy for the inhibition of osteosarcoma by pore-forming GSDME gene delivery induced enhanced pyroptosis to reshape the TME of osteosarcoma.

Immunomodulatory effect of Ti-Cu alloy by surface nanostructure synergistic with Cu2+ release.

The inflammatory response induced by implant/macrophage interaction has been considered to be one of the vital factors in determining the success of implantation. In this study, TiCuNxOy coating with an immunomodulatory strategy was proposed for the first time, using nanostructured TiCuNxOy coating synthesized on Ti-Cu alloy by oxygen and nitrogen plasma-based surface modification. It was found that TiCuNxOy coating inhibited macrophage proliferation but stimulated macrophage preferential activation and presented an elongated morphology due to the surface nanostructure. The most encouraging discovery was that TiCuNxOy coating promoted the initial pro-inflammatory response of macrophages and then accelerated the M1-to-M2 transition of macrophages via a synergistic effect of fast-to-slow Cu2+ release and surface nanostructure, which was considered to contribute to initial infection elimination and tissue healing. As expected, TiCuNxOy coating released desirable Cu2+ and generated a favorable immune response that facilitated HUVEC recruitment to the coating, and accelerated proliferation, VEGF secretion and NO production of HUVECs. On the other hand, it is satisfying that TiCuNxOy coating maintained perfect long-term antibacterial activity (≥99.9%), mainly relying on Cu2O/CuO contact sterilization. These results indicated that TiCuNxOy coating might offer novel insights into the creation of a surface with immunomodulatory effects and long-term bactericidal potential for cardiovascular applications.

Kinome-wide CRISPR-Cas9 knockout screens revealed PLK1 as a therapeutic target for osteosarcoma.

Osteosarcoma is the most common malignant bone tumor, tending to be aggressive and recurrent. The therapeutic development for treating osteosarcoma has been largely hampered by the lack of effective and specific targets. Using kinome-wide CRISPR-Cas9 knockout screens, we systematically revealed a cohort of kinases essential for the survival and growth of human osteosarcoma cells, in which Polo-like kinase 1 (PLK1) appeared as a specific prominent hit. PLK1 knockout substantially inhibited proliferation of osteosarcoma cells in vitro and the tumor growth of osteosarcoma xenograft in vivo. Volasertib, a potent experimental PLK1 inhibitor, can effectively inhibit the growth of the osteosarcoma cell lines in vitro. It can also disrupt the development of tumors in the patient-derived xenograft (PDX) models in vivo. Furthermore, we confirmed that the mode of action (MoA) of volasertib is primarily mediated by the cell-cycle arrest and apoptosis triggered by DNA damage. As PLK1 inhibitors are entering phase III clinical trials, our findings provide important insights into the efficacy and MoA of the relevant therapeutic approach for combating osteosarcoma.

Injectable chondroitin sulfate-grafted self-antioxidant hydrogels ameliorate nucleus pulposus degeneration against overactive inflammation.

Overactive inflammatory cascade accompanied by oxidative stress in the nucleus pulposus exacerbates intervertebral disc degeneration (IVDD). Hydrogels have been demonstrated to be promising in treating IVDD, yet they remain less efficacious in the case of anti-inflammation associated with antioxidation. In this study, we designed an injectable self-antioxidant hydrogel (HA/CS) with enhanced inflammation inhibitory performance for delivering chondroitin sulfate (CS) with well-documented anti-inflammatory property to treat IVDD. The hydrogel was rapidly formed via dynamic boronate ester bonding between furan/phenylboronic acid and furan/dopamine-modified hyaluronic acid (HA), and mechanically enhanced by Diels-Alder reaction-induced secondary crosslinking, partial dopamine groups of which contribute to grafting phenylboronic acid-modified CS (CS-PBA). This hydrogel exhibits favorable injectability, mechanical property, and pH-responsive delivery behavior. The dopamine moiety endows the hydrogel with efficient antioxidative property. By sustained delivery of CS, the HA/CS hydrogel is well competent to inhibit inflammatory cytokine expression and maintain anabolic/catabolic balance in an inflammation-simulated environment. Most importantly, the HA/CS hydrogel significantly ameliorates degeneration in a puncture-induced IVDD rat model. The self-antioxidant HA/CS hydrogel designed in this work may serve as a novel and promising therapeutic platform for IVDD.

Carboxypeptidase E is a prognostic biomarker co-expressed with osteoblastic genes in osteosarcoma.

Osteosarcoma (OS) is a rare primary malignant bone tumor in adolescents and children with a poor prognosis. The identification of prognostic genes lags far behind advancements in treatment. In this study, we identified differential genes using mRNA microarray analysis of five paired OS tissues. Hub genes, gene set enrichment analysis, and pathway analysis were performed to gain insight into the pathway alterations of OS. Prognostic genes were screened using the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) dataset, then overlapped with the differential gene dataset. The carboxypeptidase E (CPE) gene, found to be an independent risk factor, was further validated using RT-PCR and Gene Expression Omnibus (GEO) datasets. Additionally, we explored the specific expression of CPE in OS tissues by reanalyzing single-cell genomics. Interestingly, CPE was found to be co-expressed with osteoblast lineage cell clusters that expressed RUNX2, SP7, SPP1, and IBSP marker genes in OS. These results suggest that CPE could serve as a prognostic factor in osteoblastic OS and should be further investigated as a potential therapeutic target.

Zinc oxide nanoparticles inhibit osteosarcoma metastasis by downregulating ß-catenin via HIF-1α/BNIP3/LC3B-mediated mitophagy pathway.

Osteosarcoma (OS) therapy faces many challenges, especially the poor survival rate once metastasis occurs. Therefore, it is crucial to explore new OS treatment strategies that can efficiently inhibit OS metastasis. Bioactive nanoparticles such as zinc oxide nanoparticles (ZnO NPs) can efficiently inhibit OS growth, however, the effect and mechanisms of them on tumor metastasis are still not clear. In this study, we firstly prepared well-dispersed ZnO NPs and proved that ZnO NPs can inhibit OS metastasis-related malignant behaviors including migration, invasion, and epithelial-mesenchymal transition (EMT). RNA-Seqs found that differentially expressed genes (DEGs) in ZnO NP-treated OS cells were enriched in wingless/integrated (Wnt) and hypoxia-inducible factor-1 (HIF-1) signaling pathway. We further proved that Zn2+ released from ZnO NPs induced downregulation of ß-catenin expression via HIF-1α/BNIP3/LC3B-mediated mitophagy pathway. ZnO NPs combined with ICG-001, a ß-catenin inhibitor, showed a synergistic inhibitory effect on OS lung metastasis and a longer survival time. In addition, tissue microarray (TMA) of OS patients also detected much higher ß-catenin expression which indicated the role of ß-catenin in OS development. In summary, our current study not only proved that ZnO NPs can inhibit OS metastasis by degrading ß-catenin in HIF-1α/BNIP3/LC3B-mediated mitophagy pathway, but also provided a far-reaching potential of ZnO NPs in clinical OS treatment with metastasis.

Reduction-responsive nucleic acid nanocarrier-mediated miR-22 inhibition of PI3K/AKT pathway for the treatment of patient-derived tumor xenograft osteosarcoma.

miRNAs are important regulators of gene expression and play key roles in the development of cancer, including osteosarcoma. During the development of osteosarcoma, the expression of miR-22 is significantly downregulated, making miR-22 as a promising therapeutic target against osteosarcoma. To design and fabricate efficient delivery carriers of miR-22 into osteosarcoma cells, a hydroxyl-rich reduction-responsive cationic polymeric nanoparticle, TGIC-CA (TC), was developed in this work, which also enhanced the therapeutic effects of Volasertib on osteosarcoma. TC was prepared by the ring-opening reaction between amino and epoxy groups by one-pot method, which had the good complexing ability with nucleic acids, reduction-responsive degradability and gene transfection performance. TC/miR-22 combined with volasertib could inhibit proliferation, migration and promote apoptosis of osteosarcoma cells in vitro. The anti-tumor mechanisms were revealed as TC/miR-22 and volasertib could inhibit the PI3K/Akt signaling pathway synergistically. Furthermore, this strategy showed outstanding tumor suppression performance in animal models of orthotopic osteosarcoma, especially in patient-derived chemo-resistant and chemo-intolerant patient-derived xenograft (PDX) models, which reduced the risk of tumor lung metastasis and overcame drug resistance. Therefore, it has great potential for efficient treatment of metastasis and drug resistance of osteosarcoma by the strategy of localized, sustained delivery of miR-22 using the cationic nanocarriers combined with non-traditional chemotherapy drugs.

A high-hydrophilic Cu2O-TiO2/Ti2O3/TiO coating on Ti-5Cu alloy: Perfect antibacterial property and rapid endothelialization potential.

In order to make novel antibacterial Ti-Cu alloy more suitable for cardiovascular implant application, a Cu-containing oxide coating was manufactured on Ti-Cu alloy by plasma-enhanced oxidation deposition in plasma enhanced chemical vapor deposition (PECVD) equipment to further improve the antibacterial ability and the surface bioactivity. The results of X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and water contact angle indicated that a sustainably high-hydrophilic Cu2O-TiO2/Ti2O3/TiO coating with nano-morphology on Ti-5Cu was successfully constructed. The corrosion performance results showed that the coating enhanced the corrosion resistance while releasing more Cu2+, compared with Ti-5Cu. Antibacterial tests confirmed the perfect antibacterial property of the coating (R ≥ 99.9 %), superior to Ti-Cu alloy (R > 90 %). More delightfully, it was observed by phalloidin-FITC and DAPI staining that the coating improved the early adhesion of HUVEC cells mainly due to strong hydrophilicity and nano-morphology. It was demonstrated that the extract of the coated sample significantly promoted proliferation (RGR = 112 %-138 % after cultivation for 1 to 3 days) and migration of HUVEC cells due to the appropriate Cu2+ release concentration. Hemolysis assay and platelet adhesion results showed that the coating had excellent blood compatibility. All results suggested that the coating on Ti-Cu alloy might be a promising surface with the perfect antibacterial ability, blood compatibility and evident promoting endothelialization ability for the cardiovascular application.

Preparation of polycation with hydroxyls for enhanced delivery of miRNA in osteosarcoma therapy.

Osteosarcoma, a malignant bone tumor that usually occurs in children and adolescents, has a high rate of death and disability, bringing great pains to society and families. Improving treatment approaches for osteosarcoma patients remains a constant and major goal for researchers and clinical groups due to the limited therapeutic efficiency and survival rate. MiRNAs have been reported to play a crucial role in osteosarcoma occurrence, progression, and metastasis, which provides a new insight for osteosarcoma therapy. In other words, the intervention of the involved miRNA may be a promising way for osteosarcoma. In this study, we developed ethanolamine (EA)-decorated poly(glycidyl methacrylate) (PGMA) polycations (termed as PGEAs) to deliver miR-223 for osteosarcoma inhibition. The introduced hydroxyl groups via EA modification in the PGEA vector can form a hydration shell, hinder protein adsorption, and help the PGEA-based delivery system escape from the in vivo clearance, which further benefits the accumulation of the delivery system in the tumor area. A series of in vitro anti-tumor assays illustrate that the PGEA-2 vector can efficiently deliver miR-223 into osteosarcoma cells for impressive anti-tumor effects via inhibiting malignant behavior of osteosarcoma cells, including proliferation, migration, and invasion. Osteosarcoma inhibition assays in vivo further confirmed the anti-tumor efficiency of PGEA-2/miR-223 complexes without inducing evident toxicity. This work will help develop miRNA for osteosarcoma therapy, and the proposed PGEA based delivery system also provides a promising and safe strategy for gene therapy of osteosarcoma.

Mechanical Stimulation on Mesenchymal Stem Cells and Surrounding Microenvironments in Bone Regeneration: Regulations and Applications.

Treatment of bone defects remains a challenge in the clinic. Artificial bone grafts are the most promising alternative to autologous bone grafting. However, one of the limiting factors of artificial bone grafts is the limited means of regulating stem cell differentiation during bone regeneration. As a weight-bearing organ, bone is in a continuous mechanical environment. External mechanical force, a type of biophysical stimulation, plays an essential role in bone regeneration. It is generally accepted that osteocytes are mechanosensitive cells in bone. However, recent studies have shown that mesenchymal stem cells (MSCs) can also respond to mechanical signals. This article reviews the mechanotransduction mechanisms of MSCs, the regulation of mechanical stimulation on microenvironments surrounding MSCs by modulating the immune response, angiogenesis and osteogenesis, and the application of mechanical stimulation of MSCs in bone regeneration. The review provides a deep and extensive understanding of mechanical stimulation mechanisms, and prospects feasible designs of biomaterials for bone regeneration and the potential clinical applications of mechanical stimulation.

Polyaminoglycoside-mediated cell reprogramming system for the treatment of diabetes mellitus.

Diabetes mellitus is a disease of metabolism, featuring persistent hyperglycaemia due to insufficient insulin secretion or insulin resistance. At present, the generation of new beta cells from autologous cells by ectopic expression of specific transcription factors is a promising treatment for diabetes. The application of this strategy urgently needs safe and effective gene delivery vectors. In this work, a therapeutic plasmid (pNPMN-PBase), combined multiple specific transcription factors Ngn3, Pdx1, Mafa and Neruod1 (NPMN), was firstly constructed. Then, phenylboronic acid (PBA)-functionalized branched polymers (SS-HPT-P) have been proposed to deliver pNPMN-PBasefor the promising treatment of diabetes. SS-HPT-P had good biocompatibility and low cytotoxicity, and could achieve liver-targeted delivery. SS-HPT-P/pNPMN-PBase system can effectively realize the liver delivery of exogenous therapeutic genes, induce the reprogramming of hepatocytes into beta-like cells, reestablish the endogenous insulin-expression system, and alleviate diabetes and its complications. The present study thus provides an effective strategy for the cell replacement therapy of diabetes.