International Journal of Nanomedicine
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2024
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IF 6.6
BeiBei Lin,Peizhen Lin,Xiaobi Zhang,Yingyi Liao,Yinfei Yu,Xuegu Xu,Xiaoling Wang
Background Developing carrier-free nanomedicines via self-assembly of two antitumor drug molecules is a potential strategy for enhancing the combination treatment of tumors. Similarly, conventional chemotherapy combined with photodynamic therapy may synergistically improve the antitumor effect while minimizing the adverse reactions associated with antitumor treatment. Hyaluronic acid (HA) can bind to overexpressed HA receptors on the tumor cell surface, increasing cell internalization and resulting in good tumor-targeting properties.Methods Herein, we propose an easy and environmentally friendly approach for fabricating a novel formulation of carrier-free pure nanodrugs through self-assembly of the antitumor drug doxorubicin (DOX) and the photosensitizer chlorin e6 (Ce6), followed by sequential modification with HA to achieve simultaneous and targeted photodynamic therapy and chemotherapy.Results The fabricated HA-DOX-Ce6 nanoparticles (NPs) exhibited enhanced drug loading and stability while possessing the properties of near-infrared fluorescence imaging, self-targeting drug delivery, and combined photodynamic therapy and chemotherapy.Conclusions HA-DOX-Ce6 NPs, along with laser irradiation, effectively suppressed tumor development both in vitro and in vivo with minimal side effects. Overall, this biomaterial-based, carrier-free drug delivery system, in combination with cotargeted therapies, has shown potential for considerable improvements in treatment outcomes and patient prognosis.
研究领域:
肿瘤学
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药剂学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Qian Wang,Mingjie Chen,Junwei Yao,Gang Zhou,Dandan Zhang,Qingshan Shi,Qianwen Mai,Xiaobao Xie
The increasing prevalence of drug-resistant bacteria and the ecological burden of synthetic antimicrobials demand sustainable biomaterials with superior antibacterial properties. Natural lignin, an amorphous polymer, presents considerable potential as a structural building block for sustainable biomaterial. Herein, inspired by antimicrobial photodynamic inactivation, kraft lignin was first reacted with formaldehyde and ethylenediamine to synthesize aminated lignin, the aminated lignin was further reacted with acetic anhydride, resulting in modified lignin. Thereafter, the modified lignin functions as a carrier, encapsulating the hydrophobic photosensitizer chlorin e6 to improve its dispersibility and aqueous solubility. Chitosan was further utilized to coat the nanoparticles, improving bacterial uptake, ultimately obtaining the desired final nanospheres (CS-ML-Ce6). Upon laser irradiation, CS-ML-Ce6 achieved >99.99 % bactericidal efficiency against methicillin-resistant Staphylococcus aureus . Additionally, it demonstrated a minimum inhibitory concentration of modified lignin of 67.71 μg/mL when exposed to light. It could result in membrane disruption and intracellular component leaking, while bacterial adsorption increased to 47.36 %. The dead/live rate of CS-ML-Ce6 against drug-resistant pathogens was almost 8-fold to modified lignin control. Concurrently, hemolysis assays with rabbit red blood cells confirmed exceptional biocompatibility, with hemolysis rates maintained below 5 % even at 6 × MIC concentrations. Considerable reactive oxygen species scavenging effectiveness at both the solution and cellular levels was also observed of CS-ML- Ce6, this dual-function approach uniquely combines light-activated bactericidal properties and dark-phase antioxidant repair. Utilizing lignin, an industrial byproduct, provides an efficient and promising antimicrobial alternative to prevent overuse of antibiotics and has significant potential for human healthcare.
研究领域:
材料科学
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纳米技术
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生物医学工程
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微生物学
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光动力疗法
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高分子科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-20
·
IF 10.6
Zeng Youyun,Hu Xiangyu,Cai Zhibin,Qiu Dongchao,Ran Ying,Ding Yiqin,Shi Jiayi,Cai Xiaojun,Pan Yihuai
Background The main issues faced during the treatment of apical periodontitis are the management of bacterial infection and the facilitation of the repair of alveolar bone defects to shorten disease duration. Conventional root canal irrigants are limited in their efficacy and are associated with several side effects. This study introduces a synergistic therapy based on nitric oxide (NO) and antimicrobial photodynamic therapy (aPDT) for the treatment of apical periodontitis. Results This research developed a multifunctional nanoparticle, CGP, utilizing guanidinylated poly (ethylene glycol)-poly (ε-Caprolactone) polymer as a carrier, internally loaded with the photosensitizer chlorin e6. During root canal irrigation, the guanidino groups on the surface of CGP enabled effective biofilm penetration. These groups undergo oxidation by hydrogen peroxide in the aPDT process, triggering the release of NO without hindering the production of singlet oxygen. The generated NO significantly enhanced the antimicrobial capability and biofilm eradication efficacy of aPDT. Furthermore, CGP not only outperforms conventional aPDT in eradicating biofilms but also effectively promotes the repair of alveolar bone defects post-eradication. Importantly, our findings reveal that CGP exhibits significantly higher biosafety compared to sodium hypochlorite, alongside superior therapeutic efficacy in a rat model of apical periodontitis. Conclusions This study demonstrates that CGP, an effective root irrigation system based on aPDT and NO, has a promising application in root canal therapy.
研究领域:
牙科学
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纳米技术
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药学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2018
·Vol. 7
·期 16
·1800380
·
IF 5.609
Hao-Ran Jia,Ya-Xuan Zhu,Ke-Fei Xu,Fu-Gen Wu
Melittin (MEL) is recognized as a highly potent therapeutic peptide for treating various human diseases including cancer. However, the clinical applications of MEL are largely restricted by its severe hemolytic activity and nonspecific cytotoxicity. Here, it is found that MEL can form a stable supramolecular nanocomplex of ≈60 nm with the photosensitizer chlorin e6 (Ce6), which after hyaluronic acid (HA) coating can achieve robust, safe, and imaging-guided tumor ablation. The as-designed nanocomplex (denoted as MEL/Ce6@HA) shows largely reduced hemolysis and selective cytolytic activity toward cancer cells. Upon laser irradiation, the loaded photosensitive Ce6 can synergistically facilitate the membrane-lytic efficiency of melittin and greatly increase the tumor penetration depth of the complexes in multicellular tumor spheroids. In vivo experiments reveal that MEL/Ce6@HA can realize enhanced tumor accumulation, reduced liver deposition, and rapid body clearance, which are beneficial for highly efficient and safe chemo-photodynamic dual therapy. This work develops a unique supramolecular strategy for optimized in vivo delivery of melittin and may have implications for the development of peptide-based theranostics.
研究领域:
药学
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纳米技术
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癌症研究
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治疗学
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产品关联
DOI
PubMed
高影响因子
Nanoscale
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2020
·Vol. 12
·期 23
·12508-12521
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IF 6.895
Qian Li,Junjie Ren,Qiubing Chen,Weiwei Liu,Zhigang Xu,Yang Cao,Yuejun Kang,Peng Xue
Hollow mesoporous copper sulfide nanoparticles (HMCuS NPs) are advantageous for loading small-molecule therapeutic drugs coupled with photothermal ablation for synergistic tumor therapy. However, treatment efficacy mediated by HMCuS NPs is not always satisfactory owing to their insensitivity toward the tumor microenvironment (TME), and unpredictable drug leakage may also result in deleterious systemic toxicity. Here, a novel HMCuS@MnO2-based core–shell nanoplatform was developed as a highly efficient TME modulator, which could alleviate tumor hypoxia, deplete the level of intracellular glutathione (GSH) and trigger the dissolution of Mn2+. Moreover, MnO2, in situ grown on the surface of HMCuS, may act as a gatekeeper by forming a stimulus-responsive plug within the mesoporous structure, which effectively prevented the premature release of encapsulated photosensitizer chlorin e6 (Ce6) and was responsive to the acidic TME for demand-based drug release. Under the condition of 660/808 nm dual-wavelength laser irradiation, hyperthermia-mediated photothermal therapy (PTT) and reactive oxygen species (ROS)-mediated photodynamic therapy (PDT) can be triggered for tumor eradication, which were further enhanced upon the modification of the TME. In the meantime, splendid photoacoustic (PA)/fluorescence (FL)/magnetic resonance (MR) imaging properties of HMCuS@MnO2/Ce6 (CMC) NPs could enable the realization of more precise, reliable and on-demand combination therapy. In a word, this study illustrated a promising approach to strengthen the efficacy of HMCuS-based nanotherapeutics, which would definitely promote the further exploitation of smarter nanoplatforms for synergistic disease management.
研究领域:
纳米医学
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癌症治疗
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生物医学工程
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材料科学
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成像技术
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DOI
PubMed
高影响因子
Nanoscale
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2017
·Vol. 9
·期 17
·5551-5564
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IF 7.367
Jinping Wang,Xiaojuan Pang,Xiaoxiao Tan,Yilin Song,Li Liu,Qing You,Qi Sun,Fengping Tan,Nan Li
In this study, we report a strategy for integrating hyaluronic acid (HA), polyaniline (PANI), WS2 nanodots (WS2), and chlorin e6 (Ce6) into a single nanoplatform (HA-WS2@PANI/Ce6) for fluorescence, photoacoustic, and computed tomography multi-modality imaging-guided trimodal photothermal/radiation/photodynamic combination therapy of tumors. The WS2 nanodot core is used as the radiosensitizer with the PANI shell as the hyperthermal agent and the photosensitizer reservoir. HA and Ce6 were adsorbed on the outer shell for tumor targeting and photodynamic therapy, respectively. The in vivo trimodal imaging uncovered that HA-WS2@PANI/Ce6 nanoparticles showed enhanced tumor uptake and diagnosis effects after intravenous injection. More importantly, in the in vitro and in vivo experiments, the nanoparticles exhibited an evident near-infrared induced photothermal effect, which remarkably improved the radiation and photodynamic therapy efficiency by accelerating the blood flow and subsequently increasing oxygen supply in the tumor. The nanohybrids were found to be safe to cells in vitro and organs in vivo. Taken together, our current work demonstrates a nanoplatform for multimodal imaging guided targeted triple-therapy, which reveals a potential strategy for tumor treatment.
研究领域:
纳米技术
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生物医学工程
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癌症治疗
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医学成像
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DOI
PubMed
高影响因子
ACS Sustainable Chemistry & Engineering
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2021
·
IF 8.198
Yong-E Gao,Shengxin Hou,Jiaqi Cheng,Xinyi Li,Yongqiong Wu,Yuran Tang,Yanke Li,Peng Xue,Yuejun Kang,Zhigang Xu,Mingming Guo
With the merits of noninvasiveness, flexibility of treatment, and nonsystemic toxicity, photodynamic therapy (PDT) holds great promise in fighting against malignant cancers. Issues with conventional PDT, including severe hydrophobicity of the majority of photosensitizers (PSs), poor accumulation at the tumor site, and potential long-term side effects, greatly attenuate its therapeutic efficacy. Nanotheranostic systems are thus expected to assist our battle against cancer. Herein, we rationally designed the silk sericin (SS) based nanoparticles (designated as SSC NPs), in which photosensitizer chlorin e6 (Ce6) was conjugated with water-soluble SS via simple amidation reaction, for enhanced imaging-guided PDT. Compared with free Ce6, the as-prepared SSC NPs showed enhanced intracellular uptake efficiency and penetrability into tumor spheres. Furthermore, the SSC NPs exhibited negligible cytotoxicity toward 4T1 cells in darkness, while presenting a remarkable anticancer effect under a reduced laser power density (660 nm, 100 mW cm−2), indicating their good biocompatibility and feasibility as PDT nanoagents. Following systemic administration in 4T1 tumor-bearing mice, the SSC NPs achieved superior accumulation in tumor sites in comparison with free Ce6, which might contribute to prolonged blood circulation of nanoscale drugs. In vivo studies revealed that SSC NPs suppress the growth of tumors more effectively compared to free Ce6 and did not induce apparent side effects to the treated animals. Taken together, these results indicate that the SSC NPs have an exciting opportunity as an alternative candidate for SS-based phototherapy of cancer.
研究领域:
纳米技术
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癌症研究
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治疗诊断学
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生物医学工程
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产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2022
·
IF 11.467
Yangye Jin,Binbing Zhao,Wenjing Guo,Yuanyuan Li,Juncheng Min,Wenjun Miao
As we step into the post-antibiotic era, the accelerated emergence of antibiotic-resistant pathogenic bacteria poses an increasingly serious threat to public health. The formation of antibiotic-resistant biofilms further challenges currently available drugs and treatment options, calling for novel strategies for effective ablation of such biofilm with minimal concern on safety and development of resistance. Herein, we report a novel type of photodynamic nanoagent, composed of chlorin e6 (Ce6)-loaded water-soluble chitosan-coated iron oxide nanoparticles (named [email protected] ), for drug-resistant bacteria killing and biofilm eradication. The fabricated [email protected] has negligible toxicity to mammalian cells and exhibited equivalent singlet oxygen generation capacity to free Ce6; however, its association with methicillin-resistant Staphylococcus aureus (MRSA) was greatly enhanced, as evidenced by flow cytometry analysis and transmission electron microscope. In vitro studies verified that [email protected] has superior photodynamic bactericidal effect against planktonic MRSA. Furthermore, with the aid of the cationic nature and small size, [email protected] could effectively penetrate into MRSA biofilm, revealed by 3D fluorescence imaging. Both biomass analysis and viable bacteria counting demonstrated that [email protected] showed potent biofilm ablation efficacy, averagely 7.1 log unit lower than that in free Ce6 group upon identical light irradiation. In addition, local treatment of MRSA-infected mice with [email protected] plus light irradiation resulted in significant antibacterial and wound healing effect, accompanied by good biocompatibility in vivo. Collectively, photosensitizer-loaded cationic IONP with effective biofilm penetration and photodynamic eradication potential might be a promising nano platform in fighting against antibiotic-resistant microbial pathogen and biofilm.
研究领域:
纳米技术
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药学
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生物医学工程
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微生物学
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传染病学
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DOI
PubMed
高影响因子
Materials Today Nano
·
2025
·
IF 8.2
Xinyu Mao,Shiwei Liu,Xinhao Li,Menghui Zhang,Peng Shen,Yaning Zhu,Xiaozhong Yang
Colorectal cancer (CRC) is the third most prevalent malignancy globally. Its tumor microenvironment (TME) heterogeneity and chemotherapy resistance compromise the efficacy of conventional treatments such as surgery and chemotherapy. This study developed a multifunctional nanotherapeutic platform by synthesizing mesoporous silica nanoparticles (MSNs) via a modified Stöber method. The carboxylated MSN surface was sequentially loaded with metformin (Me), chlorin e6 (Ce6), and glucose oxidase (GO X ), constructing an Me/Ce6@MSN-GO X (MCMG) nanosystem. The synthesized MSNs demonstrated excellent porosity, pore volume, and high loading capacity. In vitro and in vivo studies showed that MCMG reversed the Warburg effect via the AMPK/ACC/mTOR axis, reprogrammed tumor energy metabolism, and enhanced GO X -induced starvation therapy and Ce6-based photodynamic therapy (PDT). MCMG also alleviated TME hypoxia by suppressing HIF-1α expression, inducing an approximately 2-fold increase in intracellular reactive oxygen species levels and culminating in a 71% tumor inhibition rate in vivo. This platform integrated Me’s metabolic regulation with Ce6-mediated PDT and GO X -driven starvation therapy to achieve synergistic CRC eradication. MCMG enables multifunctional theranostics through synergistic mechanisms (metabolic modulation, oxidative damage, and nutrient deprivation) coupled with fluorescence imaging capabilities, presenting a novel strategy for CRC treatment.
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产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2021
·Vol. 9
·期 17
·3677-3688
·
IF 6.331
Lei Zhang,Ruihao Yang,Honglian Yu,Zhigang Xu,Yuejun Kang,Hongjuan Cui,Peng Xue
Silk fibroin (SF), derived from Bombyx mori, is a category of fibrous protein with outstanding potential for applications in the biomedical and biotechnological fields. In spite of its many advantageous properties, the exploration of SF as a versatile nanodrug precursor for tumor therapy has still been restricted in recent years. Herein, a multifunctional SF-derived nanoplatform was facilely developed via encapsulating the photosensitizer chlorin e6 (Ce6) into MnO2-capped SF nanoparticles (NPs). SF@MnO2 nanocarriers were synthesized through a surface crystallization technique, using SF as a reductant and sacrificial template. Afterwards, Ce6 was covalently incorporated into the loose structure of the SF@MnO2 nanocarrier on the basis of adsorption to abundant peptide-binding sites. To modulate the tumor microenvironment (TME), SF@MnO2/Ce6 (SMC) NPs were capable of catalyzing the decomposition of H2O2 into O2, which can be converted into cytotoxic reactive oxygen species (ROS) during photodynamic therapy (PDT). Moreover, the MnO2 component was able to oxidize intracellular glutathione (GSH) into non-reducing glutathione disulfide (GSSG), and the consumption of GSH could significantly protect the local ROS from being reduced, which further augmented the therapeutic outcome of PDT. Via another angle, SMC NPs can produce strong hyperthermia under near-infrared (NIR) light activation, which was highly desirable for efficient photothermal therapy (PTT). Both in vitro and in vivo studies demonstrated the intense tumor inhibitory effects as a result of augmented PTT/PDT mediated by SMC NPs. We believe that this study may provide useful insights for employing SF-based nanocomposites for more medical applications in the near future.
研究领域:
生物医学工程
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纳米医学
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癌症治疗
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材料科学
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DOI
PubMed
高影响因子
Small
·
2021
·Vol. 17
·期 10
·2007953
·
IF 13.281
Cheng Wang,Shaoqing Chen,Fangying Yu,Jianghong Lv,Rui Zhao,Fuqiang Hu,Hong Yuan
A conventional theranostic system usually employs a single fluorescence channel to show the pharmacokinetic events, which usually fails to quantitatively reveal the true cumulative drug release and with low accuracy. Herein, indocyanine green (ICG) and chlorins e6 (Ce6) are selected not only as conventional photothermal/photodynamic agents, but also to offer two independent fluorescence channels to cross validate the authenticity of pharmacokinetic events and to quantitatively reveal cumulative drug release in tumor tissues in a “turn on” manner. Employing the Ca 2+ of amorphous calcium carbonate as a reversible linker, the photosensitivity and fluorescence of Ce6 are physically quenched by ICG during circulation to reduce the side effect of photodynamic therapy (PDT) while being readily restored in tumor tissue to reveal the quantitative drug release. Most importantly, the combination of photothermal therapy (PTT) and PDT allows low-temperature synergistic therapy of cancer through the controlled expression of heat shock protein in cells and mild hyperthermia enhanced reactive oxygen species diffusion/penetration among cells. This work not only develops a facile approach to fabricate a dual-channel theranostic system to precisely indicate the accumulation and quantitative drug release in tumor tissue, but also presents a unique low-temperature synergistic strategy to destroy tumor in an effective and minimally invasive manner.
研究领域:
癌症治疗
·
生物医学工程
·
药学
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纳米技术
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诊疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NANOTECHNOLOGY
·
2020
·Vol. 31
·期 19
·195103
·
IF 3.551
Junlong Liang,Xiaokang Jin,Biling Chen,Jinhua Hu,Qianwei Huang,Junmin Wan,Zhiwen Hu,Bing Wang
The integration of chemotherapy drugs and photosensitizers to form versatile nanoplatforms for achieving chemo-photodynamic synergetic therapy has shown great superiority in tumor theranostic applications. We constructed pH-responsive nanoparticles (DOX/PB NPs) encapsulating the chemotherapeutic drug doxorubicin (DOX) into the cores of PLGA NPs coated with bovine serum albumin (BSA) via a water-in-oil (W/O/W) emulsion method. A simple and efficient chemo-photodynamic synergetic nanoplatform (DOX/PB@Ce6 NPs) was obtained by the adsorption of photosensitizer chlorin e6 (Ce6) onto the surface of the DOX/PB NPs. With optimal size, pH-responsive drug release behavior and excellent singlet oxygen production, the DOX/PB@Ce6 NPs have the potential to enhance anti-tumor efficiency. The cellular uptake, cytotoxicity, chemo-photodynamic synergetic effect and biocompatibility of the NPs were evaluated based on HeLa cells via in vitro experiments. The in vitro chemo-photodynamic synergetic experiments indicated that the DOX/PB@Ce6 NPs had remarkable cancer cell killing efficiency under laser irradiation. Notably, by hemolysis assay, all the NPs displayed excellent blood compatibility and were expected to be applicable for intravenous injection. In summary, the designed DOX/PB@Ce6 NPs multifunctional theranostic nanoplatform had excellent reactive oxygen species generation and would be a potential therapeutic platform for chemo-photodynamic synergetic therapy.
研究领域:
纳米技术
·
药学
·
癌症研究
·
生物医学工程
·
诊疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）