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International Journal of Nanomedicine · 2023 · IF 8

Combination of Chemotherapy and Photodynamic Therapy with Oxygen Self-Supply in the Form of Mutual Assistance for Cancer Therapy

Ying Chen,Lei Zhang,Fangxuan Li,Jindong Sheng,Changxiao Xu,Dan Li,Hu Yu,Wenxin Liu

Introduction Photodynamic therapy (PDT) has been widely researched by cancer therapists in recent years. This study aims to establish a drug delivery system combining PDT and chemotherapy to show that chemotherapeutic drugs provide oxygen to PDT, while PDT promotes the release of chemotherapeutic drug.Methods Firstly, poly(ethylene glycol)-lysine(Ce6)-block-poly(L-glutamate)-imidazole (mPEG-lys(Ce6)-PGA-AIM) was synthesized and self-assembled into micelles that exhibited pH- and ROS-responsiveness and buffering capacity. Perfluorohexanoate-modified cisplatin (FCP), as oxygen carriers, was encapsulated into mPEG-lys(Ce6)-PGA-AIM micelles. Then, the properties of micelles and their biological functions in vivo and in vitro were investigated.Results The micelles exhibited remarkabe stability, pH regulated drug release, good biocompatibility and effective tumor penetration. Cellular uptake demonstrated the efficient endosome/lysosome escape of CFMs, which facilitates the intracellular drug release. Both in vitro and in vivo experiments reflected that CFMs with laser irradiation showed significantly improved therapeutic activity compared with single PDT or chemotherapy.Conclusion Chemotherapy and PDT were combined in the form of mutual assistance to provide a promising strategy for clinical treatment.

CAS / MDL: 109-89-7 32315-10-9
研究领域: 肿瘤学 · 药学 · 生物医学工程
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BIOMATERIALS · 2024 · IF 12.8

VEGF-loaded ROS-responsive nanodots improve the structure and function of sciatic nerve lesions in type II diabetic peripheral neuropathy.

Xiaolan Ou,Ze Wang,Daojiang Yu,Wenlai Guo,Andrei V. Zvyagin,Quan lin,Wenrui Qu

ABSTRACT Diabetic peripheral neuropathy (DPN) is a prevalent complication of diabetes mellitus (DM), significantly contributing to the risk of amputation and mortality. Reactive oxygen species (ROS) can induce both neurological and structural harm through direct impact and pyroptosis, underscoring the critical role of ROS regulation in mitigating DPN. In this research endeavor, we propose harnessing the inherent antioxidant properties of sulfhydryl groups by grafting them onto gold nanodots through an amidation reaction, resulting in the creation of ROS-responsive AuNDs. Additionally, we aim to synthesize AuNDs-VEGF, wherein VEGF is attached to AuNDs via electrostatic interactions, as a therapeutic strategy for addressing DPN in rat models. The results of in vivo experiments showed that AuNDs and AuNDs-VEGF nanoparticles could increase the nerve conduction velocity, shorten the latency of nerve conduction in the sciatic nerve, promote the regeneration of nerve trophectodermal vessels, improve the structure and function of the sciatic nerve, reduce the apoptosis of neural cells, and alleviate the atrophy of the gastrocnemius muscle. Thus, VEGF-loaded ROS-responsive nanodots present a promising avenue for ameliorating diabetic peripheral neuropathy. This innovative approach not only extends the application possibilities of nanodots but also introduces a novel avenue for the treatment of diabetic neuropathy.

CAS / MDL: 25952-53-8 6066-82-6
研究领域: 纳米技术 · 神经科学 · 糖尿病研究 · 药学 · 生物医学工程
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ACS Omega · 2024 · IF 3.7

Dynamic-Covalent Mesoporous Silica Nanohybrid with pH/ROS-Responsive Drug Release for Targeted Tumor Therapy

Yurong Leng,Yanmei Wu,Wenjing Xiao,Xiaoquan Su,Zhe Liu

Nanomedicine provides promising new methodologies for the treatment of tumors but still faces several limitations, including poor colloidal stability, uncontrollable drug release, and insufficient drug targeting. Herein, hyaluronic acid (HA) was used to modify the surface of mesoporous silica nanoparticles (MSNs) via a dynamic-covalent linker, phenylborate ester (PBAE), termed MA. The HA modifier provided enhanced colloidal stability to the hybrid nanoparticles. As expected, MA exhibited an improved biocompatibility and high potential for biomedical applications. Moreover, MA with a negatively charged surface effectively adsorbed the drug Doxorubicin (DOX) inside the carriers, ensuring minimal drug leakage. In an acidic and reactive oxygen species (ROS)-containing condition mimicking the tumor microenvironment, MA@DOX (MAD) continuously released its payloads, likely due to the cleavage of the pH/ROS-sensitive PBAE. Compared with free DOX, MAD had 2.2 times higher accessibility to tumor cells than free DOX. The favorable stability and cancer-selective drug release make this nanoformulation a promising platform for potent cancer treatment.

CAS / MDL: 14047-29-1 67-68-5
研究领域: 纳米医学 · 药学 · 癌症治疗 · 材料科学
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JOURNAL OF CONTROLLED RELEASE · 2024 · IF 10.5

ROS-responsive nanoparticle delivery of obeticholic acid mitigate primary sclerosing cholangitis

Qigu Yao,Beiduo Wang,Jiong Yu,Qiaoling Pan,Yingduo Yu,Xudong Feng,Wenyi Chen,Jinfeng Yang,Changyou Gao,Hongcui Cao

Primary sclerosing cholangitis (PSC) is a challenging cholestatic liver disease marked by progressive bile duct inflammation and fibrosis that has no FDA-approved therapy. Although obeticholic acid (OCA) has been sanctioned for PSC, its clinical utility in PSC is constrained by its potential hepatotoxicity. Here, we introduce a novel therapeutic construct consisting of OCA encapsulated within a reactive oxygen species (ROS)-responsive, biodegradable polymer, further cloaked with human placenta-derived mesenchymal stem cell (hP-MSC) membrane (MPPFTU@OCA). Using PSC patient-derived organoid models, we assessed its cellular uptake and cytotoxicity. Moreover, using a PSC mouse model induced by 3,5-diethoxycarbonyl-1,4-dihydro-collidine (DDC), we demonstrated that intravenous administration of MPPFTU@OCA not only improved cholestasis via the FXR-SHP pathway but also reduced macrophage infiltration and the accumulation of intracellular ROS, and alleviated mitochondria-induced apoptosis. Finally, we verified the ability of MPPFTU@OCA to inhibit mitochondrial ROS thereby alleviating apoptosis by measuring the mitochondrial adenosine triphosphate (ATP) concentration, ROS levels, and membrane potential (ΔΨm) using H 2 O 2 -stimulated PSC-derived organoids. These results illuminate the synergistic benefits of integrating an ROS-responsive biomimetic platform with OCA, offering a promising therapeutic avenue for PSC.

研究领域: 药理学 · 肝病学 · 纳米技术 · 干细胞生物学
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NEW JOURNAL OF CHEMISTRY · 2024 · IF 2.7

ROS-responsive polymeric micelles with aggregation-induced emission effects for drug delivery and cellular imaging

Xiaoyi Song,Fan Yang,Ruixuan Ji,Bin Yang,Yin Lv,Zhong Wei

Traditional chemotherapy faces challenges related to limited drug efficacy and adverse reactions. Intelligent nanocarrier drug delivery systems (INDDSs) promise improved treatment outcomes with reduced toxicity. However, several clinical challenges persist in achieving rapid drug release and real-time monitoring. Herein, a ROS-responsive amphiphilic copolymer was synthesized: polyethylene glycol (mPEG-TK-OH) with ROS-responsive thioketal (TK) as the macromolecular initiator, and enzymatic ring-opening polymerization of caprolactone was performed. Small molecules of tetraphenylethylene (TPE) with aggregation-induced emission (AIE) properties were added to the polymer's terminus to enable fluorescence imaging and the ROS-responsive amphiphilic copolymer mPEG-TK-PCL-TPE with AIE properties is formed and enhances drug release monitoring through fluorescence resonance energy transfer (FRET) between TPE and the hydrophobic anti-cancer drug DOX. Leveraging distinct ROS levels between tumor and normal cells, these ROS-responsive nanomicelles effectively respond to high intracellular redox-active species and release DOX. The mPEG-TK-PCL-TPE micelles displayed a suitable size, high drug loading, and excellent imaging quality. In vitro cell experiments confirmed their biocompatibility and efficacy in inhibiting 4T1 tumor cells. This ROS-responsive amphiphilic copolymer, incorporating the AIE structure, introduces new opportunities for cancer treatment, enabling real-time drug release tracking and improving therapeutic outcomes.

研究领域: 纳米技术 · 药学 · 生物医学工程 · 癌症研究
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RSC Advances · 2019 ·Vol. 9 ·期 16 ·9260-9269 · IF 3.049

Polydopamine-modified ROS-responsive prodrug nanoplatform with enhanced stability for precise treatment of breast cancer

Bin Yang,Kaiyuan Wang,Dong Zhang,Bin Ji,Dongyang Zhao,Xin Wang,Haotian Zhang,Qiming Kan,Zhonggui He,Jin Sun

Development of smart stimuli-responsive prodrug nanomaterials for fast drug release and efficient antitumor therapy has attracted great attention in recent years. However, the inherent instability of naked prodrugs in the blood is an important challenge limiting their biomedical applications. Although a number of strategies have been taken to prevent prodrugs from hydrolyzing due to blood composition, most of these strategies are unsatisfactory. Here, we designed an extraordinary ROS-triggered prodrug nanoplatform fabricated by using a single thioether linker to conjugate PTX with 6-maleimidocaproic acid (MAL), resulting in the PTX-S-MAL prodrug self-assembling into uniform size nanoparticles; then the prodrug nanoplatform was modified with a polydopamine coating and PEGylation to confer high solubility and stability. In in vitro experiments, the polydopamine-modified ROS-responsive prodrug nanosystem showed a high sensitivity in term of various H2O2 concentrations, and the PDA coating on the surface of the prodrug nanosystem didn't affect the drug release properties. Moreover, the excellent polydopamine-modified ROS-triggered prodrug nanoplatform selectively and rapidly releases PTX in response to the ROS overproduced in tumor cells, but showed less cytotoxicity against normal cells. In in vivo experiments, the prepared polydopamine-modified prodrug-nanosystem obviously enhances the stability and tumor accumulation of prodrug, producing a remarkably improved breast cancer treatment with minimal side effects. Our studies demonstrated that this modified nanoplatform could significantly improve chemotherapy efficiency, which will find great potential in cancer treatment.

CAS / MDL: 107-21-1
研究领域: 纳米技术 · 药学 · 癌症研究 · 药物递送系统
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ACS Applied Materials & Interfaces · 2021 · IF 9.229

Dual-Responsive and ROS-Augmented Nanoplatform for Chemo/Photodynamic/Chemodynamic Combination Therapy of Triple Negative Breast Cancer

Mengyao Chen,Jingxian Yang,Lulu Zhou,Xiaochun Hu,Chunhui Wang,Keke Chai,Ruihao Li,Lei Feng,Yanting Sun,Chunyan Dong,Shuo Shi

Integrating chemodynamic therapy (CDT) and photodynamic therapy (PDT) into one nanoplatform can produce much more reactive oxygen species (ROS) for tumor therapy. Nevertheless, it is still a great challenge to selectively generate sufficient ROS in tumor regions. Meanwhile, CDT and PDT are restricted by insufficient H2O2 content in the tumor as well as by the limited tumor tissue penetration of the light source. In this study, a smart pH/ROS-responsive nanoplatform, Fe2+@UCM-BBD, is rationally designed for tumor combination therapy. The acidic microenvironment can induce the pH-responsive release of doxorubicin (DOX), which can induce tumor apoptosis through DNA damage. Beyond that, DOX can promote the production of H2O2, providing sufficient materials for CDT. Of note, upconversion nanoparticles at the core can convert the 980 nm light to red and green light, which are used to activate Ce6 to produce singlet oxygen (1O2) and achieve upconversion luminescence imaging, respectively. Then, the ROS-responsive linker bis-(alkylthio)alkene is cleaved by 1O2, resulting in the release of Fenton reagent (Fe2+) to realize CDT. Taken together, Fe2+@UCM-BBD exhibits on-demand therapeutic reagent release capability, excellent biocompatibility, and remarkable tumor inhibition ability via synergistic chemo/photodynamic/chemodynamic combination therapy.

研究领域: 癌症治疗 · 纳米技术 · 药学 · 生物医学工程
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CHEMICAL ENGINEERING JOURNAL · 2023 · IF 15.1

ROS-Responsive and Self-Amplifying polymeric prodrug for accelerating infected wound healing

Yingwen Lu,Pengfei Shan,Weilin Lu,Xiangping Yin,Haiwei Liu,Xiaoyue Lian,Jiayi Jin,Yuxi Qi,Zhongyu Li,Zhihui Li

Bacterial infection is a serious global health threat, and the clinical abuse of antibiotics has severe systemic toxicity and leads to multidrug-resistant bacteria. Stimuli-responsive polymers represent an encouraging strategy for intelligent treatment; however, inadequate polymer degradation and drug release are still challenging, especially in bacterial infection, where exponential rates of degradation and release are urgently needed. Here, we reported a facile 1,1,3,3-tetramethylguanidine (TMG)-promoted polyesterification method for the preparation of a novel antibiotic-free, PEGylated ROS-responsive polymeric prodrug of cinnamaldehyde (PRPCA), and demonstrated its remarkable intrinsic antibacterial activities and the acceleration of infected wound healing for the first time. The CA was covalently incorporated into the backbone of the polyester by a ROS-responsive thioacetal linkage and can be triggered to release by the ROS generated during bacterial growth. The released CA successively induced more ROS generation and the polymer achieved self-accelerating degradation via the positive feedback. The PRPCA-based nanomedicine possessed great bactericidal effects against both S. aureus and E. coli in vitro . Strikingly, the self-amplifying degradation of PRPCA nanoparticles caused abrupt “self-destruction” of S. aureus . More importantly, PRPCA significantly accelerated the S. aureus -infected wound healing process without systematic toxicity. Collectively, this work opens an avenue to develop novel self-amplifying stimuli-responsive polymers based on natural antimicrobial for superior wound disinfection and healing.

研究领域: 药学 · 材料科学 · 生物医学工程 · 纳米技术 · 传染病学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2025 · IF 8.5

A TME-responsive polysaccharide nanoplatform integrating synergetic therapy for cancer

Wenhui Liu,Ruyu Cao,Yongye Shen,Yaxin Lu,Shuqi Li,Shen Li,Guochen Su,Jing Xu,Yuanqiang Guo

A self-assembling nanoplatform based on FOB (a heteropolysaccharide from Fomitopsis officinalis ) named QU@FOB-FcDBA was developed in this study. A dynamic boronate ester bond, a pH-sensitive covalent linkage formed through reversible dehydration reactions, linked FOB and 1,1′-ferrocenediboronic acid (FcDBA) while encapsulating the hydrophobic drug quercetin (QU). The formulation not only enhanced the water solubility of QU, but also indirectly improved the clinical utilization rate of QU. QU@FOB-FcDBA exhibited unique dual pH/ROS-responsive characteristics, enabling precise recognition and selective response to the acidic microenvironment and elevated reactive oxygen species (ROS) levels in tumor tissues. This ensured the accurate and controlled release of QU and FcDBA, achieving synergistic deep penetration and enhanced therapeutic efficacy through the combined induction of ferroptosis and chemotherapy. In vivo , QU@FOB-FcDBA effectively suppressed tumor progression and metastasis. Mechanistically, it induced cell death via multiple pathways: triggering ferroptosis through ROS accumulation, lipid peroxidation (LPO), and glutathione (GSH) depletion, as well as inducing apoptosis. In vitro , FOB upregulated macrophage surface markers (CD40, CD80, CD86, MHC-II) and nitric oxide (NO) expression. This innate immune activation may directly contribute to antitumor effects and establish a favorable immune microenvironment for immunotherapy. These results position QU@FOB-FcDBA as a promising platform integrating ferroptosis induction and chemotherapy for improved cancer treatment.

CAS / MDL: 117-39-5 571203-78-6
研究领域: 纳米医学 · 癌症治疗 · 药物递送 · 生物化学 · 免疫学 · 药理学 · 材料科学
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Journal of Materials Chemistry B · 2024 · IF 6.1

Microenvironment-responsive release of Mg2+ from tannic acid decorated and multilevel crosslinked hydrogel accelerates infected wound healing

Na Li,Yi Cao,Jingyi Liu,Wen Zou,Manyu Chen,Hongfu Cao,Siyan Deng,Jie Liang,Tun Yuan,Yujiang Fan,Qiguang Wang,Xingdong Zhang

The management of chronic infected wounds poses significant challenges due to frequent bacterial infections, high concentrations of reactive oxygen species, abnormal immune regulation, and impaired angiogenesis. This study introduces a novel, microenvironment-responsive, dual dynamic, and covalently bonded hydrogel, termed OHA-P-TA/G/Mg2+. It is derived from the reaction of Tannic acid (TA) with Phenylboronic acids (PBA), which are grafted onto oxidized hyaluronic acid (OHA-P-TA), combined with GelMA (G) via Schiff base and chemical bonds, and incorporates Mg2+. This hydrogel exhibits pH and ROS dual-responsiveness, demonstrating effective antibacterial capacity, antioxidant ability, and the initiation of inflammation under distinct acidic and oxidative microenvironments. Furthermore, the release of Mg2+ from the TA-Mg2+ network (TA@Mg2+) promotes the transformation of pro-inflammatory M1 phenotype macrophages to anti-inflammatory M2 phenotype, showing a microenvironment-responsive response. Finally, in vivo results indicate that the OHA-P-TA/G/Mg2+ hydrogel enhances epithelial regeneration, collagen deposition, and neovascularization, showing great potential as an effective dressing for infected wound repair.

CAS / MDL: 30418-59-8 6066-82-6
研究领域: 材料科学 · 生物医学工程 · 伤口愈合 · 药剂学
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ACS Applied Materials & Interfaces · 2021 · IF 9.229

ROS-Responsive Nanoparticle as a Berberine Carrier for OHC-Targeted Therapy of Noise-Induced Hearing Loss

Zeqi Zhao,Zhengzhong Han,Konduru Naveena,Guanxiong Lei,Shiwei Qiu,Xuanyi Li,Ting Li,Xi Shi,Wei Zhuang,Yalan Li,Yuehua Qiao,Hongmei Liu

Overproduction of reactive oxygen species (ROS) and inflammation are two key pathogeneses of noise-induced hearing loss (NIHL), which leads to outer hair cell (OHC) damage and hearing loss. In this work, we successfully developed ROS-responsive nanoparticles as berberine (BBR) carriers (PL-PPS/BBR) for OHC-targeted therapy of NIHL: Prestin-targeting peptide 2 (PrTP2)-modified nanoparticles (PL-PPS/BBR), which effectively accumulated in OHC areas, and poly(propylene sulfide)120 (PPS120), which scavenged ROS and converted to poly(propylene sulfoxide)120 in a ROS environment to disintegrate and provoke the rapid release of BBR with anti-inflammatory and antioxidant effects. In this study, satisfactory anti-inflammatory and antioxidant effects of PL-PPS/BBR were confirmed. Immunofluorescence and scanning electron microscopy (SEM) images showed that PL-PPS/BBR effectively accumulated in OHCs and protected the morphological integrity of OHCs. The auditory brainstem response (ABR) results demonstrated that PL-PPS/BBR significantly improved hearing in NIHL guinea pigs after noise exposure. This work suggested that PL-PPS/BBR may be a new potential treatment for noise-associated injury with clinical application.

CAS / MDL: 8002-43-5
研究领域: 药理学 · 纳米技术 · 耳科学 · 听力学
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Advanced Materials Interfaces · 2023 · IF 5.4

Preparation of ROS-Responsive Exosome Coating of Nitinol Material for Making the Neurointerventional Stent

Lin Duan,Yanyan He,Haigang Wu,Tianxiao Li,Jia Liang,Rufeng Jia,Dehua Guo,Taoyuan Lu,Chi Ma,Wenbo Liu,Yingkun He

Nitinol (NiTi) alloy is an ideal material for preparing neurointerventional stents due to its excellent mechanical properties and biocompatibility. However, NiTi stents without surface-specific functionalization cause a high rate of stent thrombosis and in-stent restenosis after implantation. In ischemic stroke, exosomes have a role in regulating nervous system development, regeneration, vascular remodeling, and neuroinflammation. In this work, the effect of exosome coating on the biocompatibility of NiTi alloy is evaluated. NiTi alloy is successively immersed in relevant solution (sodium alginate, 3-aminophenylboronic acid, distearoylphosphatidylethanolamine, and exosomes) to form ROS-responsive exosome coated surfaces. In vitro experiments (platelets, endothelial cells, smooth muscle cells, and macrophages) and in vivo subcutaneous implantation experiments are performed to test coatings for biocompatibility. The results show that the modified NiTi alloy surface has high hydrophilicity, which has the functions of inhibiting platelet aggregation, promoting endothelialization, inhibiting smooth muscle cell migration, anti-inflammatory, and good tissue biocompatibility. This study develops exosome neurointerventional stent coating as a bioactive drug via reactive oxygen species accumulation in lesions, thus targeting drug release, inhibiting intimal hyperplasia, and reducing inflammation and thrombosis.

CAS / MDL: 6066-82-6 9005-38-3
研究领域: 材料科学 · 生物医学工程 · 神经科学 · 生物材料 · 组织工程
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