BIOMATERIALS
·
2020
·
IF 10.317
Chengli Yang,Yuyin Fu,Cheng Huang,Danrong Hu,Kai Zhou,Ying Hao,Bingyang Chu,Yun Yang,Zhiyong Qian
Photodynamic therapy (PDT) is a relatively safe and clinically promising treatment to combat primary tumors, especially epidermal carcinoma, while has negligible effects on distant metastasis. Therefore, this work reports a multifunctional nanosystem ( [email protected] ) exerting a combined photodynamic and immunotherapy to amplify the therapeutic effect on primary tumors and distant metastasis. Specifically, this nanosystem was obtained by electrostatic adsorption of a negatively charged hyaluronic acid “shell” with a positively charged “core” consisting of the CRISPR-Cas9 system targeting the Ptpn2 gene (Cas9-Ptpn2) and a modified mitochondria-targeting chlorin e6 (TPP-PEI-Ce6). Cell experiments demonstrated that the [email protected] nanoparticles possessed very high transfection efficiency on B16F10 cells, and TPP-PEI-Ce6 in the nanoparticles resulted in a significant PDT efficacy due to the efficient singlet oxygen generation in mitochondria under laser-irradiation. The accumulation of the nanoparticles in the tumor by active and passive tumor-targeting in vivo led to the disruption of the Ptpn2 gene by the Cas9-Ptpn2 plasmids in the nanocarriers, thus sensitizing tumors to immunotherapy by the increase of the IFN-γ and TNF-α signaling and the promotion of the proliferation of CD8 + T cells . In addition, Hyaluronidase was administered in advance to destroy the hyaluronic acid in the condensed extracellular matrix and to remove the hyaluronic acid “shell” from the nanosystem, subsequently leading to an enhanced penetration of oxygen and therapeutic agents. Fortunately, the primary and distant tumors in the experimental animals were remarkably inhibited after the combination of PDT-immunotherapy, thus, this easy-to-built nanomedicine could be used as a potential combination therapy against tumors.
研究领域:
癌症治疗
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纳米技术
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分子生物学
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免疫学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2024
·
IF 5.3
Feiyang Xu,Ting Cui,Jun Wang,Wanzhen Li,Yuan Gao,Xing Li,Kai Yang,Weiwei Zhang,Fei Ge,Yugui Tao
The increasing prevalence of multidrug-resistant (MDR) bacteria primarily due to the emergence of drug-resistant biofilms that have rendered current antimicrobial agents ineffective poses a significant concern in public health. Therefore, innovative antimicrobial agents need to be urgently developed. This study aimed to design a photodynamic antimicrobial nanocomposite (Ce6/HSF) based on chitosan quaternary ammonium salt (HTCC)-functionalized silk fibroin (SF) loaded with chlorin e6 (Ce6) for eliminating drug-resistant biofilms and bacteria. The prepared Ce6/HSF had low toxicity, good biocompatibility, and excellent ability to generate single-linear-state oxygen. In addition, Ce6/HSF can enter multidrug-resistant bacteria by electrostatic adsorption due to its small size and cationic nature. Furthermore, it effectively promoted wound healing in mice infected with MDR Staphylococcus aureus.
研究领域:
生物材料学
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微生物学
·
医学
✓ 已验证
产品关联
DOI
高影响因子
BIOMATERIALS
·
2018
·
IF 8.806
Baiping Mao,Caixia Liu,Wenwen Zheng,Xiaoheng Li,Renshan Ge,Haifa Shen,Xiaoling Guo,Qingquan Lian,Xian Shen,Chao Li
Regenerated silk fibroin (SF) is a natural biomacromolecule with excellent biocompatible and biodegradable properties. In this study, cyclic pentapeptide cRGDfk and Chlorin e6 (Ce6) were conjugated to SF polypeptides , and genipin was used to prepare 5-fluorouracil (5-FU) doped SF-based nanoparticles (NPs). The photodynamic therapy (PDT) potential and active targeting properties were systematically investigated in α v β 3 integrin receptor over-expressed MGC-803 cells in vitro. The results revealed that treatment with the multifunctional SF-based NPs and PDT, high level of reactive oxygen species (ROS) and cell death can be induced in MGC-803 cells. Combine with PDT, the in vivo antitumor effect of the SF-based NPs was evaluated in gastric cancer xenograft mice model. The results demonstrated that the SF-based NPs had ideal active tumor targeting property and the tumor burden can be reduced noticeably. Furthermore, the organs of mice in SF NPs treatment groups did not show obvious toxicity, demonstrating good biocompatibility and security profiles of SF NPs in vivo. Overall, our results suggest that the SF-based NPs are promising drug delivery carriers, together with PDT, the multimodality therapy could be potential regimen in future clinical cancer treatment.
研究领域:
生物医学工程
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肿瘤学
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药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanomedicine
·
2019
·
IF 4.717
Qian Li,Mengmeng Hou,Junjie Ren,Shiyu Lu,Zhigang Xu,Chang Ming Li,Yuejun Kang,Peng Xue
Aim: Hollow mesoporous copper sulfide nanocapsules conjugated with poly(ethylene glycol) (PEG), doxorubicin and chlorin e6 (HPDC) were synthesized for fluorescence imaging and multimodal tumor therapy. Materials & methods: HPDC were synthesized by encapsulating chlorin e6 and doxorubicin into PEGylated nanocapsules via a simple precipitation method. The photothermal/photodynamic effects, drug release, cellular uptake, imaging capacities and antitumor effects of the HPDCs were evaluated. Results: This smart nanoplatform is stimulus-responsive toward an acidic microenvironment and near infrared laser irradiation. Moreover, fluorescence imaging-guided and combined photothermal/photodynamic/chemotherapies of tumors were promoted under laser activation and led to efficient tumor ablation, as evidenced by exploring animal models in vivo. Conclusion: HPDCs are expected to serve as potent and reliable nanoagents for achieving superior therapeutic outcomes in cancer management.
研究领域:
纳米医学
·
肿瘤学
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生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2016
·
IF 7.145
Wenxiu Hou,Fangfang Xia,Carla S. Alves,Xiaoqing Qian,Yuming Yang,Daxiang Cui
A unique matrix metalloproteinase 2-targeted photosensitizer delivery platform was developed in this study for tumor-targeting imaging and photodynamic therapy. The model photosensitizer therapeutic agent chlorin e6 (Ce6) was first covalently conjugated with matrix metalloproteinase 2-cleavable polypeptide and then modified with polyethylene glycol via a redox-responsive cleavable disulfide linker. The resultant matrix metalloproteinase 2-cleavable polypeptide modified PEGylated Ce6 (PEG-SS-Ce6-MMP2) nanoparticles, which formed via self-assembly, were observed to be monodisperse and significantly stable in aqueous solution. In addition, owing to their cellular redox-responsiveness at the cleavable disulfide linker, the PEG-SS-Ce6-MMP2 nanoparticles were able to release Ce6 rapidly. Despite displaying enhanced intracellular internalization, the synthesized PEG-SS-Ce6-MMP2 nanoparticles did not compromise their phototoxic effects toward A549 cancer cells when compared with free Ce6 and PEGylated Ce6 nanoparticles. In vivo experiments further revealed that, in contrast with the free Ce6 or with the PEGylated Ce6 nanoparticles, the PEG-SS-Ce6-MMP2 nanoparticles showed a remarkable increase in tumor-targeting ability and a significantly improved photodynamic therapeutic efficiency in A549 tumor-bearing mice. These results suggest that the PEG-SS-Ce6-MMP2 nanoparticles hold great potential for tumor-targeting imaging and photodynamic therapy.
研究领域:
纳米医学
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癌症研究
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诊疗学
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药学
✓ 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
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药学
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癌症研究
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生物医学工程
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诊疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Chinese Medicine
·
2023
·Vol. 18
·期 1
·1-14
·
IF 4.9
Guo Zhaopei,Wong Ka Hong,Li Enze,Zhou Xingzhi,Jiang Di,Gao Jiebing,Chen Meiwan
Background The integration of photodynamic therapy with a chemical drug-delivery system has displayed great potential in enhancing anticancer therapy. However, the solubility and non-specific biodistribution of both chemotherapeutic agents and photosensitizers continue to pose challenges that hinder their clinical applications.MethodA polypeptide-based nanoscale drug delivery system was fabricated to address the prementioned issues. An amphiphilic polymer was formed by conjugating the photosensitizer chlorin e6 (Ce6) onto a polypeptide poly-(L-lysine)-b-polyphenylalanine (PKF) for encapsulating the model drug dimeric camptothecin (DCPT), and the nanoparticles (PCD) with high drug loading efficiency were further modified with acid-sensitive polyethylene glycol (PEG) to yield the drug delivery sytem (PPCD).Results The DCPT and Ce6 encapsulation efficiency were analyzed as 99% and 73.5%, respectively. In phosphate-buffered saline (PBS) solution at a pH of 7.4, the PEG shell improved the stability of micelles and shielded their positive charge while in the acidic tumor microenvironment, the pH-sensitive PEG layer was removed to expose the cationic nanoparticles, thus facilitating the cellular uptake of PPCD micelles. Benefiting from the enhanced cellular internalization, the amount of intracellular reactive oxygen species (ROS) treated with PCD and PPCD micelles were obviously increased. Furthermore, the enhanced anti-cancer efficacy prompted by PPCD micelles was validated through cellular and animal study.Conclusion This study presents a promising method to promote the solubility and biodistribution of both chemotherapeutic agent and photosensitizer, thereby facilitating the further application of chemo-photodynamic cancer therapy.Graphical Abstract
研究领域:
癌症治疗
·
纳米技术
·
药剂学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS APPLICATIONS
·
2018
·
IF 2.082
Jing-Hua Sun,Wei Zhang,Dong-Yang Zhang,Jianliang Shen,Cai-Ping Tan,Liang-Nian Ji,Zong-Wan Mao
A multimodal nanocarrier based on mesoporous silica nanoparticles (MSNs) is developed to co-delivery photosensitizer chlorin e6 (Ce6) and chemotherapeutic agent doxorubicin (Dox) for cancer combination therapy. Ce6 was covalently conjugated with mesoporous silica nanoparticles, which could increase the loading efficiency, and allowed for photodynamic therapy. Doxorubicin was loaded into the pores of mesoporous silica nanoparticles to afford the dual drug delivery system Dox@MSNs-Ce6. These hybrid nanoparticles have an average diameter of about 100 nm and slightly negative charge of about −17 mV. The Dox@MSNs-Ce6 nanoparticles could efficiently enter into cancer cells. The cellular reactive oxygen species level in treated cells increased about 17 times, upon 660 nm light irradiation (10 mW/cm2, 2 min). More importantly, Dox@MSNs-Ce6 exhibited excellent synergistic effect through combining chemotherapy and photodynamic therapy against A549 lung cancer cells. Our work provides an effective strategy for anticancer drug delivery and combination therapy.
研究领域:
药剂学
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR LIQUIDS
·
2022
·
IF 6.633
Yuchi Zhang,Nan Zhang,Shiyuan Yao,Chenyu Yao,Yawen Li,Mengyun Ke,Sufeng Zhang,Liwei Qian,Xiaoling Hu,Fenggang Ren
In the field of cancer therapy, photodynamic therapy (PDT) is an emerging treatment modality that utilized light, photosensitizers (PSs), and oxygen to generate reactive oxygen species (ROS) to destroy tumor sites selectively. Conventional PSs experience issues such as poor water solubility and low bioavailability. The widely developed PS delivery nanosystems can address these problems, but most of them usually depend on relatively complex components and time-consuming synthesis procedures. Therefore, PS delivery vehicles with more easily obtained components and simpler preparation methods need to be explored. In this study, amphiphilic and cationic single-isomer cyclodextrin (CD-IL) was designed, which could co-assemble with chlorin e6 (Ce6, a commercially available PS) via multiple non-covalent interactions. The obtained nanovesicles (CD-CE) could not only overcome the inherent drawbacks of free Ce6, but also exhibit improved PDT efficacy in a series of cell-related experiments, including favorable stability, preferable cellular uptake, and enhanced phototoxicity. Thus, CD-CE prepared by the co-assembly of simple building blocks could be a facile option for PDT clinical applications.
研究领域:
药学
·
肿瘤学
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纳米医学
✓ 已验证
产品关联
DOI
高影响因子
ACS Infectious Diseases
·
2025
·
IF 3.8
Feiyang Xu,Ting Cui,Zhendong Long,Haidong Shen,Hong Xie,Hongfu Liu,Jianfei Xie,Kai Yang,Yugui Tao
The development of drug-resistant biofilms has resulted in treatment failures for multidrug resistant (MDR) bacteria, presenting a substantial challenge to global public health. Consequently, the development of antibacterial agents has become an urgent priority. To overcome the limitations of poor penetration and inadequate efficacy of single-modal treatments for MDR bacterial biofilm infections, this study developed a Ce6/SFP nanocomposite system utilizing silk fibroin and polydopamine. The nanoparticles, fabricated via a desolvation-in situ polymerization method, demonstrated pH-responsive drug release properties. When subjected to an 808 nm NIR laser, the material exhibited a photothermal conversion efficiency of 29.3%. Furthermore, when paired with singlet oxygen produced through 660 nm excitation, it was highly effective in eliminating MDR Escherichia coli and MDR Staphylococcus aureus. The synergistic effect of photothermal therapy (PTT) and photodynamic therapy (PDT) disrupted the stability of the cell membrane and enhanced the antibacterial efficacy. Experimental results showed that the photothermal effect increased biofilm permeability, significantly improving Ce6 penetration depth. Moreover, in vivo treatments exhibited accelerated wound healing. Biocompatibility assessments revealed a hemolysis rate below 5% and no pathological damage to major organs. This study proposes a synergistic strategy to effectively address the challenges posed by biofilms and bacterial resistance.
研究领域:
医学
·
材料科学
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生物工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Composites and Hybrid Materials
·
2025
·Vol. 8
·期 1
·1-21
·
IF 21.8
Zhou Qiang,Shubhra Quazi T. H.,Lai Peng,Shi Jiayi,Fang Chenhao,Guo Qian,Li Wanqing,Chen Rui,Shen Xinkun,Huang Lina,Cai Xiaojun,Lin Sen
Nasopharyngeal carcinoma (NPC) is an epithelial malignancy with a poor prognosis that is usually advanced at the time of diagnosis. Photodynamic therapy (PDT), with its safety and reproducibility, offers significant potential for advanced NPC treatment, though its efficacy is hindered by the hypoxic tumor microenvironment and continuous oxygen depletion during therapy. This study presents a versatile nanoformulation (CGP) co-loaded with chlorin e6 (Ce6) and genistein (Gen) within peptide dendritic nanogel (PDN) for enhanced NPC treatment. The positively charged CGP is efficiently internalized by NPC cells, followed by glutathione (GSH)-responsive degradation, releasing Ce6 and Gen. The released Gen reduces intracellular oxygen consumption and tumor metastability by inhibiting the HIF-1 signaling pathway, thereby efficiently boosting PDT efficacy. In vitro and in vivo studies confirmed that the combination of Gen and PDT effectively eliminates tumors and inhibits metastasis. Multi-omics analysis (RNA sequencing and targeted energy metabolomics) revealed that CGP suppresses HIF-1α, GLUT1, and VEGFA expression, downregulating the HIF-1 pathway and reducing anaerobic glycolysis, thereby successfully remodeling the hypoxia-associated tumor microenvironment. This study demonstrates that the Gen-PDT combination is a versatile approach capable of enhancing PDT efficacy and holds promise for NPC management.
研究领域:
肿瘤学
·
药学
·
分子生物学
·
癌症治疗
✓ 已验证
产品关联
DOI
高影响因子
International Journal of Nanomedicine
·
2024
·
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
·
药剂学
·
生物医学工程
✓ 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）