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Journal Name:Biomaterials Science
Journal ISSN:2047-4830
IF:7.59
Journal Website:http://pubs.rsc.org/en/Journals/JournalIssues/bm#!recentarticles&adv
Year of Origin:0
Publisher:Royal Society of Chemistry (RSC)
Number of Articles Per Year:265
Publishing Cycle:
OA or Not:Not
Progress of cell membrane-derived biomimetic nanovesicles for cancer phototherapy
Biomaterials Science ( IF 7.59 ) Pub Date : 2023-09-13 , DOI: 10.1039/D3BM01170D
Faisal Raza,Hajra Zafar,Liangdi Jiang,Jing Su,Weien Yuan,Mingfeng Qiu
In recent years, considerable attention has been given to phototherapy, including photothermal and photodynamic therapy to kill tumor cells by producing heat or reactive oxygen species (ROS). It has the high merits of noninvasiveness and limited drug resistance. To fully utilize this therapy, an extraordinary nanovehicle is required to target phototherapeutic agents in the tumor cells. Nanovesicles embody an ideal strategy for drug delivery applications. Cell membrane-derived biomimetic nanovesicles represent a developing type of nanocarrier. Combining this technique with cancer phototherapy could enable a novel strategy. Herein, efforts are made to describe a comprehensive overview of cell membrane-derived biomimetic nanovesicles for cancer phototherapy. The description in this review is mainly based on representative examples of exosome-derived biomimetic nanomedicine research, ranging from their comparison with traditional nanocarriers to extensive applications in cancer phototherapy. Additionally, the challenges and future prospectives for translating these for clinical application are discussed.
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Enhancing cell-scale performance via sustained release of the varicella-zoster virus antigen from a microneedle patch under simulated microgravity†
Biomaterials Science ( IF 7.59 ) Pub Date : 2023-12-12 , DOI: 10.1039/D3BM01440A
Yue Yin,Junyuan Yang,Ge Gao,Huaijuan Zhou,Bowen Chi,Hong Yu Yang,Jinhua Li,Yilong Wang
The immune system of astronauts might become weakened in the microgravity environment in space, and the dormant varicella-zoster virus (VZV) in the body might be reactivated, seriously affecting their work and safety. For working in orbit for the long term, there is currently no efficient and durable delivery system of general vaccines in a microgravity environment. Accordingly, based on the previous foundation, we designed, modified, and synthesized a biodegradable and biocompatible copolymer, polyethylene glycol-polysulfamethazine carbonate urethane (PEG-PSCU) that could be mainly adopted to fabricate a novel sustained-release microneedle (S-R MN) patch. Compared with conventional biodegradable microneedles, this S-R MN patch could not only efficiently encapsulate protein vaccines (varicella-zoster virus glycoprotein E, VZV gE) but also further prolong the release time of VZV gE in a simulated microgravity (SMG) environment. Eventually, we verified the activation of dendritic cells by VZV gE released from the S-R MN patch in an SMG environment and the positive bioeffect of activated dendritic cells on lymphocytes using an in vitro lymph node model. This study is of great significance for the exploration of long-term specific immune responses to the VZV in an SMG environment.
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Improving combination cancer immunotherapy by manipulating dual immunomodulatory signals with enzyme-triggered, cell-penetrating peptide-mediated biomodulators†
Biomaterials Science ( IF 7.59 ) Pub Date : 2023-12-17 , DOI: 10.1039/D3BM01605F
Guibin Pang,Piao Chen,Huan Yu,Leshuai W. Zhang
Immunosuppressive tumor microenvironments challenge the effectiveness of protein-based biopharmaceuticals in cancer immunotherapy. Reestablishing tumor cell immunogenicity by enhancing calreticulin (CRT) exposure is expected to improve tumor immunotherapy. Given that CRT translocation is inherently modulated by phosphorylated eIF2α, the selective inhibition of protein phosphatase 1 (PP1) emerges as an effective strategy to augment tumor immunogenicity. To harness the PP1-disrupting potential of GADD34-derived motifs and address their limited intracellular delivery, we integrated these sequences into an enzyme-triggered, cell-penetrating peptide-mediated chimeric protein scaffold. This design not only facilitates efficient cytoplasmic delivery of these immunostimulatory motifs to induce “eat-me” signaling, but also provides a versatile platform for combination immunotherapy. Fabrication of biomodulators with cytotoxic BLF1 provides additional “eat-me” signaling through phosphatidylserine exposure or that with an immunomodulatory designed ankyrin repeat protein disables “don't-find-me” signaling by antagonizing PD-L1. Notably, these bifunctional biomodulators exhibit remarkable ability to induce macrophage phagocytosis, dendritic cell maturation, and CD8+ T activation, ultimately substantially inhibiting tumor growth. This study presents a modular genetic coding strategy for PP1-centered therapies that enables seamless integration of immunostimulatory sequences into protein-based anti-tumor cocktail therapies, thereby offering novel alternatives for improving antitumor efficacy.
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Correction: An E-selectin targeting and MMP-2-responsive dextran–curcumin polymeric prodrug for targeted therapy of acute kidney injury
Biomaterials Science ( IF 7.59 ) Pub Date : 2024-01-19 , DOI: 10.1039/D4BM90007C
Di Liu,Jing Qi,Kong-jun Lu,Fei-yang Jin,Xiao-Ying Ying,Jian You,Yong-Zhong Du
Correction for ‘An E-selectin targeting and MMP-2-responsive dextran–curcumin polymeric prodrug for targeted therapy of acute kidney injury’ by Jing-Bo Hu et al., Biomater. Sci., 2018, 6, 3397–3409, https://doi.org/10.1039/C8BM00813B.
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Microfluidics: a concise review of the history, principles, design, applications, and future outlook
Biomaterials Science ( IF 7.59 ) Pub Date : 2023-11-27 , DOI: 10.1039/D3BM01463K
Mohammad Irfan Hajam,Mohammad Mohsin Khan
Microfluidic technologies have garnered significant attention due to their ability to rapidly process samples and precisely manipulate fluids in assays, making them an attractive alternative to conventional experimental methods. With the potential for revolutionary capabilities in the future, this concise review provides readers with insights into the fascinating world of microfluidics. It begins by introducing the subject's historical background, allowing readers to familiarize themselves with the basics. The review then delves into the fundamental principles, discussing the underlying phenomena at play. Additionally, it highlights the different aspects of microfluidic device design, classification, and fabrication. Furthermore, the paper explores various applications, the global market, recent advancements, and challenges in the field. Finally, the review presents a positive outlook on trends and draws lessons to support the future flourishing of microfluidic technologies.
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Research progress and perspective of metallic implant biomaterials for craniomaxillofacial surgeries
Biomaterials Science ( IF 7.59 ) Pub Date : 2024-01-03 , DOI: 10.1039/D2BM01414A
Huafang Li,Jiaqi Hao,Xiwei Liu
Craniomaxillofacial bone serves a variety of functions. However, the increasing number of cases of craniomaxillofacial bone injury and the use of selective rare implants make the treatment difficult, and the cure rate is low. If such a bone injury is not properly treated, it can lead to a slew of complications that can seriously disrupt a patient's daily life. For example, premature closure of cranial sutures or skull fractures can lead to increased intracranial pressure, which can lead to headaches, vomiting, and even brain hernia. At present, implant placement is one of the most common approaches to repair craniomaxillofacial bone injury or abnormal closure, especially with biomedical metallic implants. This review analyzes the research progress in the design and development of degradable and non-degradable metallic implants in craniomaxillofacial surgery. The mechanical properties, corrosion behaviours, as well as in vitro and in vivo performances of these materials are summarized. The challenges and future research directions of metallic biomaterials used in craniomaxillofacial surgery are also identified.
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Drug delivery nanoparticles for preventing implant bacterial infections based on the bacteria and immunity mechanisms†
Biomaterials Science ( IF 7.59 ) Pub Date : 2023-11-21 , DOI: 10.1039/D3BM01584J
Chen Chen,Qi Xiao,Leyi Xiao,Mengge Feng,Fangzhe Liu,Ke Yao,Yu Cui,Tiange Zhang
Implant dysfunction and failure during medical treatment can be attributed to bacterial infection with Staphylococcus aureus and Enterococcus faecalis, which are the prevalent strains responsible for implant infections. Currently, antibiotics are primarily used either locally or systemically to prevent and treat bacterial infections in implants. However, the effectiveness of this approach is unsatisfactory. Therefore, the development of new antimicrobial medications is crucial to address the clinical challenges associated with implant infections. In this study, a nanoparticle (ICG+RSG) composed of indocyanine green (ICG) and rosiglitazone (RSG), and delivered using 1,2-dipalmitoyl-snglycero-3-phosphocholine (DPPC) was prepared. ICG+RSG has photothermal and photodynamic properties to eliminate bacteria at the infection site by releasing reactive oxygen species and increasing the temperature. Additionally, it regulates phagocytosis and macrophage polarization to modulate the immune response in the body. ICG+RSG kills bacteria and reduces tissue inflammation, showing potential for preventing implant infections.
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Front cover
Biomaterials Science ( IF 7.59 ) Pub Date : 2024-01-30 , DOI: 10.1039/D4BM90008A
A graphical abstract is available for this content
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Enhancing drug delivery with supramolecular amphiphilic macrocycle nanoparticles: selective targeting of CDK4/6 inhibitor palbociclib to melanoma†
Biomaterials Science ( IF 7.59 ) Pub Date : 2023-12-11 , DOI: 10.1039/D3BM01888A
Mohamed F. Attia,Edikan A. Ogunnaike,Megan Pitz,Nancy M. Elbaz,Dillip K. Panda,Angela Alexander-Bryant,Sourav Saha,Daniel C. Whitehead
Drug delivery systems based on amphiphilic supramolecular macrocycles have garnered increased attention over the past two decades due to their ability to successfully formulate nanoparticles. Macrocyclic (MC) materials can self-assemble at lower concentrations without the need for surfactants and polymers, but surfactants are required to form and stabilize nanoparticles at higher concentrations. Using MCs to deliver both hydrophilic and hydrophobic guest molecules is advantageous. We developed two novel types of amphiphilic macrocycle nanoparticles (MC NPs) capable of delivering either Nile Red (NR) (a hydrophobic model) or Rhodamine B (RhB) (a hydrophilic model) fluorescent dyes. We extensively characterized the materials using various techniques to determine size, morphology, stability, hemolysis, fluorescence, loading efficiency (LE), and loading capacity (LC). We then loaded the CDK4/6 inhibitor Palbociclib (Palb) into both MC NPs using a solvent diffusion method. This yielded Palb-MC NPs in the size range of 65–90 nm. They exhibited high stability over time and in fetal bovine serum with negligible toxicity against erythrocytes. Cytotoxicity was minimal when tested against RAW macrophages, human fibroblast HDFn, and adipose stromal cells (ASCs) at higher concentrations of MC NPs. Cell viability studies were conducted with different concentrations of MC NPs, Palb-MC NPs, and free Palb against RAW macrophages, human U-87 GBM, and human M14 melanoma cell lines in vitro. Flow cytometry experiments revealed that blank MC NPs and Palb-MC NPs were selectively targeted to melanoma cells, resulting in cell death compared to the other two cell lines. Future work will focus on studying the biological effect of MC NPs including their binding affinity with molecules/receptors expressed on the M14 and other melanoma cell surfaces by molecular docking simulations. Subsequently, we will evaluate the MCs as a component of combination therapy in a murine melanoma model.
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Single atom nanozymes for bacterial infection therapy
Biomaterials Science ( IF 7.59 ) Pub Date : 2023-11-22 , DOI: 10.1039/D3BM01838E
Xing Lan,Miaomiao Chen,Xin He,Shutao Gao,Xinghua Zhao
Bacterial infection-related diseases continue to pose a significant challenge to global human health. Antibiotic therapy, as a conventional therapeutic strategy, has been extensively employed in clinical settings to treat bacterial infections. However, the effectiveness of these conventional strategies is often impeded by the antimicrobial resistance of bacteria. Consequently, the development of alternative antibacterial agents has emerged as a promising approach to addressing this issue. In recent years, single-atom nanozymes (SAzymes), a novel class of nanocatalytic medicines, have garnered increasing attention due to their numerous advantages, including uniformly dispersed metal active sites, tunable coordination structures, and maximal metal atomic utilization efficiency. To date, a variety of SAzymes have been developed and widely applied in antibacterial therapy. In this minireview, we provide an overview of the latest advances in the synthesis and antibacterial application of different metal-based SAzymes. Furthermore, we discuss the future challenges and opportunities of utilizing SAzymes for bacterial infection treatment. It is our hope that this minireview will contribute to the development of the next generation of SAzyme-based antibacterial agents.
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GSH/pH dual responsive chitosan nanoparticles for reprogramming M2 macrophages and overcoming cancer chemoresistance†
Biomaterials Science ( IF 7.59 ) Pub Date : 2023-12-19 , DOI: 10.1039/D3BM01741A
Xinzhi Zhao,Ying Wang,Jialei Hao,Yang Liu
The combination of two or more drugs with different mechanisms of action is a promising strategy for circumventing multidrug resistance (MDR). However, the antitumor effect of nanosystems is usually limited due to the simultaneous release of different payloads at a single location rather than at their respective sites of action. Herein, we report a GSH and pH dual responsive nanoplatform encapsulated with doxorubicin (DOX) and resiquimod (R848) (GPNP) for combinatorial chemotherapy against cancer cells with drug resistance. GPNP possesses a core–shell structure wherein the polymer shell detaches in the acidic and sialic acid (SA)-rich environment. This leads to the release of R848 into the tumor microenvironment (TME), thereby reprogramming M2 macrophages into M1 macrophages and exposing the core CS(DOX)-PBA to kill MCF-7/ADR cells. Additionally, the nitric oxide (NO) generated by M1 macrophages can suppress the P-glycoprotein (P-gp) expression to reduce the efflux of chemotherapy drugs, thus playing a combined role in overcoming MDR. In vitro studies have demonstrated the effectiveness of GPNP in reprogramming M2 macrophages and inducing apoptosis in MCF-7/ADR cells, resulting in enhanced antitumor efficacy. This work proposed an effective combination strategy to combat chemoresistance, providing new insights into the development of innovative combinatorial therapies against MDR tumors.
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Pristine gelatin incorporation as a strategy to enhance the biofunctionality of poly(vinyl alcohol)-based hydrogels for tissue engineering applications†
Biomaterials Science ( IF 7.59 ) Pub Date : 2023-10-31 , DOI: 10.1039/D3BM01172K
Alessia Longoni,Gretel S. Major,Shaoyuan Jiang,Brooke L. Farrugia,David C. Kieser,Tim B. F. Woodfield,Jelena Rnjak-Kovacina
Synthetic polymers, such as poly(vinyl alcohol) (PVA), are popular biomaterials for the fabrication of hydrogels for tissue engineering and regenerative medicine (TERM) applications, as they provide excellent control over the physico-chemical properties of the hydrogel. However, their bioinert nature is known to limit cell-biomaterial interactions by hindering cell infiltration, blood vessel recruitment and potentially limiting their integration with the host tissue. Efforts in the field have therefore focused on increasing the biofunctionality of synthetic hydrogels, without limiting the advantages associated with their tailorability and controlled release capacity. The aim of this study was to investigate the suitability of pristine gelatin to enhance the biofunctionality of tyraminated PVA (PVA-Tyr) hydrogels, by promoting cell infiltration and host blood vessel recruitment for TERM applications. Pure PVA-Tyr hydrogels and PVA-Tyr hydrogels incorporated with vascular endothelial growth factor (VEGF), a well-known pro-angiogenic stimulus, were used for comparison. Incorporating increasing concentrations of VEGF (0.01–10 μg mL−1) or gelatin (0.01–5 wt%) did not influence the physical properties of PVA-Tyr hydrogels. However, their presence within the polymer network (>0.1 μg mL−1 VEGF and >0.1 wt% gelatin) promoted endothelial cell interactions with the hydrogels. The covalent binding of unmodified gelatin or VEGF to the PVA-Tyr network did not hamper their inherent bioactivity, as they both promoted angiogenesis in a chick chorioallantoic membrane (CAM) assay, performing comparably with the unbound VEGF control. When the PVA-Tyr hydrogels were implanted subcutaneously in mice, it was observed that cell infiltration into the hydrogels was possible in the absence of gelatin or VEGF at 1- or 3-weeks post-implantation, highlighting a clear difference between in vitro an in vivo cell-biomaterial interaction. Nevertheless, the presence of gelatin or VEGF was necessary to enhance blood vessel recruitment and infiltration, although no significant difference was observed between these two biological molecules. Overall, this study highlights the potential of gelatin as a standalone pro-angiogenic cue to enhance biofunctionality of synthetic hydrogels and provides promise for their use in a variety of TERM applications.
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Back cover
Biomaterials Science ( IF 7.59 ) Pub Date : 2024-01-30 , DOI: 10.1039/D4BM90010C
A graphical abstract is available for this content
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Implantable bioelectrodes: challenges, strategies, and future directions
Biomaterials Science ( IF 7.59 ) Pub Date : 2023-12-07 , DOI: 10.1039/D3BM01204B
Mengyuan Hu,Chunyong Liang,Donghui Wang
Implantable bioelectrodes for regulating and monitoring biological behaviors have become indispensable medical devices in modern healthcare, alleviating pathological symptoms such as epilepsy and arrhythmia, and assisting in reversing conditions such as deafness and blindness. In recent years, developments in the fields of materials science and biomedical engineering have contributed to advances in research on implantable bioelectrodes. However, the foreign body reaction (FBR) is still a major constraint for the long-term application of electrodes. In this paper, four types of commonly used implantable bioelectrodes are reviewed, concentrating on their background, development, and a series of complications caused by FBR after long-term implantation. Strategies for resisting FBRs are then devised in terms of physics, chemistry, and nanotechnology. We analyze the major trends in the future development of implantable bioelectrodes and outline some promising research to optimize the long-term operational stability of electrodes. Although current implantable bioelectrodes have been able to achieve good biocompatibility, low impedance, and low mechanical mismatch and trauma, these devices still face the challenge of FBR. Resistance to FBR is still the key for the long-term effectiveness of bioelectrodes, and a better understanding of the mechanisms of FBR, as well as miniaturization, long-term passivation, and coupling with gene therapy may be the way forward for the next generation of implantable bioelectrodes.
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Advances in biomedical systems based on microneedles: design, fabrication, and application
Biomaterials Science ( IF 7.59 ) Pub Date : 2023-11-07 , DOI: 10.1039/D3BM01551C
Xinghao Wang,Zifeng Wang,Min Xiao,Zhanhong Li,Zhigang Zhu
Wearable devices have become prevalent in biomedical studies due to their convenient portability and potential utility in biomarker monitoring for healthcare. Accessing interstitial fluid (ISF) across the skin barrier, microneedle (MN) is a promising minimally invasive wearable technology for transdermal sensing and drug delivery. MN has the potential to overcome the limitations of conventional transdermal drug administration, making it another prospective mode of drug delivery after oral and injectable. Subsequently, combining MN with multiple sensing approaches has led to its extensive application to detect biomarkers in ISF. In this context, employing MN platforms and control schemes to merge diagnostic and therapeutic capabilities into theranostic systems will facilitate on-demand therapy and point-of-care diagnostics, paving the way for future MN technologies. A comprehensive analysis of the growing advances of microneedles in biomedical systems is presented in this review to summarize the latest studies for academics in the field and to offer for reference the issues that need to be addressed in MN application for healthcare. Covering an array of novel studies, we discuss the following main topics: classification of microneedles in the biomedical field, considerations of MN design, current applications of microneedles in diagnosis and therapy, and the regulatory landscape and prospects of microneedles for biomedical applications. This review sheds light on the significance of microneedle-based innovations, presenting an analysis of their potential implications and contributions to the community of wearable healthcare technologies. The review provides a comprehensive understanding of the field's current state and potential, making it a valuable resource for academics and clinicians seeking to harness the full potential of MN applications.
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Surface functionalization of endotracheal tubes coated with laccase–gadolinium phosphate hybrid nanoparticles for antibiofilm activity and contrasting properties†
Biomaterials Science ( IF 7.59 ) Pub Date : 2023-12-14 , DOI: 10.1039/D3BM01406A
Somayeh Mojtabavi,Seyed Ali Asghar Fakhrmousavi,Mehrdad Faizi,Hamid Forootanfar,Nasrin Samadi,Mohammad Ali Faramarzi
Ventilator-associated pneumonia (VAP) is a severe hospital-acquired infection that endangers patients’ treatment in intensive care units (ICUs). One of the leading causes of VAP is biofilm formation on the endotracheal tube (ETT) during ventilation. This study reports a combination of laccase–gadolinium phosphate hybrid nanoparticles (laccase@GdPO4·HNPs) and enzyme mediator with an antibiofilm property coated on the surface of the ETT. The hybrid nanostructures were fabricated through a simple, rapid, and facile laccase immobilization method, resulting in efficiency and yield percentages of 82 ± 6% and 83 ± 5%, respectively. The surface of the ETT was then functionalized and coated with the constructed HNP/catechol. The layered ETT was able to reduce the surface adhesion of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus by 82.1%, 84.5%, and 77.1%, respectively. The prepared ETT did not affect the viability of human lung epithelial cells L929 and A549 at concentrations of 1–5 mg mL−1. The layered ETT produced a strong computed tomography (CT) signal in comparison with iobitridol. The HNP/catechol-coated ETT exhibited a Gd3+ release of 0.45 ppm over 72 h, indicating reduced risks of cytotoxicity arising from the metal ions. In this research we develop a biofilm-resistant and contrasting agent-based ETT coated with green synthesized laccase@GdPO4·HNPs.
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Platelet membrane-based biochemotactic-targeting nanoplatform combining PDT with EGFR inhibition therapy for the treatment of breast cancer†
Biomaterials Science ( IF 7.59 ) Pub Date : 2023-12-05 , DOI: 10.1039/D3BM01627G
Guoyun Wan,Xuheng Chen,Ruiling Gou,Chenguang Guan,Jiayu Chen,Qian Wang,Qiqing Zhang,Haijiao Wang
Presently, the commonly used anti-tumor drugs lack targeting ability, resulting in a limited therapeutic efficacy and significant side effects. In this view, platelet membranes (PMs) not only exhibit specific binding of its P-selectin protein with CD44, which is highly expressed on breast cancer cells, to promote tumor-active targeting by PM biomimetic nanoplatforms, but also respond to vascular damage, thus inducing biochemotactic targeting to further facilitate the aggregation of these nanoplatforms. Therefore, in this study, a PM was applied to construct a biochemotactic-targeting nanotherapeutic platform based on dendritic large pore mesoporous silica nanoparticles (DLMSNs) co-loaded with chlorin e6 (Ce6) and lapatinib (LAP) to achieve the combination of photodynamic therapy (PDT) and EGFR inhibition therapy for breast cancer. Under laser irradiation, PM@DLMSN/Ce6/Lap could not only effectively kill breast tumor cells by the PDT, but also damage blood vessels. By combining the EGFR inhibition of LAP, PM@DLMSN/Ce6/Lap could better inhibit the migration and movement of tumor cells. In vitro and in vivo results showed that PM@DLMSN/Ce6/Lap could achieve active-targeting drug delivery to breast tumors and further recruit more nanoparticles to accumulate at tumor sites after the PDT-induced damage of blood vessels through biochemotactic targeting, achieving continuous EGFR inhibition to prevent tumor proliferation and metastasis. In conclusion, this study not only provides a new strategy for the clinical treatment of breast cancer, but also provides a design idea for improving the targeted delivery of anti-tumor drugs.
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A stable ratiometric fluorescent probe for hypochlorous acid detection and rheumatoid arthritis evaluation†
Biomaterials Science ( IF 7.59 ) Pub Date : 2023-12-21 , DOI: 10.1039/D3BM01576A
Liuwei Gu,Yinghao Li,Xiaojie Kong,Ke Zhang,Yuling Qin,Xiaobo Zhou,Haiwei Ji,Guo Li,Li Wu
A ratiometric fluorescent probe (MeO-CNPPV Pdots) based on the principle of fluorescence resonance energy transfer (FRET) was designed for hypochlorous acid (HOCl) and rheumatoid arthritis (RA) detection. The presence of HOCl can block the energy transfer from CNPPV to MeOTPATBT, resulting in a ratio change in the fluorescence of Pdots (I600 nm/I680 nm). This strategy provides a valuable paradigm in early RA evaluation.
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Contents list
Biomaterials Science ( IF 7.59 ) Pub Date : 2024-01-30 , DOI: 10.1039/D4BM90009J
The first page of this article is displayed as the abstract.
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An active transport dual adaptive nanocarrier designed to overcome the corneal microenvironment for neovascularization therapy†
Biomaterials Science ( IF 7.59 ) Pub Date : 2023-11-10 , DOI: 10.1039/D3BM01349A
Yingying Li,Shan Gao,Yu Zhang,Zhijing He,Jianbo Ji,Xiaoye Yang,Lei Ye,Lixia Zhao
The eyes have a complicated microenvironment with many clearance mechanisms, making it challenging for effective drug delivery to the targeted areas of the eyes. Substrate transport mediated by active transporters is an important way to change drug metabolism in the ocular microenvironment. We designed multifunctional, dual-adaptive nanomicelles (GSCQ@NTB) which could overcome multiple physiological barriers by acting on both the efflux transporter and influx transporter to achieve deep delivery of the P-gp substrate in the cornea. Specifically, an effective “triple” antiangiogenic agent, nintedanib (NTB), was loaded into the biocompatible micelles. The expression of the efflux transporter was reversed by grafting quercetin. The peptide (glycylsarcosine, GS) was modified to target the influx transporter “Peptide Transporter-1” (PepT-1). Quercetin (QRT) and nintedanib (NTB) were transported to the cornea cooperatively, achieving long retention on the ocular surface and high compatibility. In a New Zealand rabbit model, within 8 hours after local administration, GSCQ@NTB was enriched in corneal stromal neovascularization and effectively inhibited the progress of neovascularization. Its effectiveness is slightly better than that in the first-line clinical application of steroids. In this study, we introduce the preparation of a dual adaptive nano-micelle system, which may provide an effective non-invasive treatment for corneal neovascularization.
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