Biomaterials Science
·
2022
·Vol. 11
·期 1
·162-169
·
IF 7.59
Ren-Jiang Kong,Xin-Yu Li,Jia-Qi Huang,Xiang Zhou,Fu-An Deng,Yan-Mei Li,Ling-Shan Liu,Shi-Ying Li,Hong Cheng
Tumor cells activate DNA repair pathways to combat the oxidative damage induced by reactive oxygen species (ROS), contributing to their resistance to photodynamic therapy (PDT). Herein, a self-delivery photodynamic sensitizer is developed to enhance oxidative damage by blocking the DNA repair pathway through poly(ADP-ribose) polymerase (PARP) inhibition. Specifically, the photodynamic sensitizer (CeOla) is constructed based on the self-assembly of the photosensitizer chlorine e6 (Ce6) and the PARP inhibitor olaparib (Ola). Of note is that carrier free CeOla has a high drug content and favorable water stability, which could be effectively internalized by tumor cells for robust PDT upon light irradiation. Moreover, CeOla could inhibit the activation of PARP, promote the upregulation of γ-H2AX and reduce the expression of Rad51, thereby blocking the DNA repair pathway to sensitize tumor cells for PDT. As a consequence, the self-delivery CeOla greatly promotes the tumor cell apoptosis and shows a high antitumor performance with low side effects. It serves as a novel platform for the development of self-delivery nanomedicine to overcome oxidative resistance in tumor treatment.
研究领域:
肿瘤学
·
药理学
·
纳米医学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE & TECHNOLOGY
·
2023
·
IF 10.9
Di Chuan,Huan Hou,Yuelong Wang,Min Mu,Jinglun Li,Yangmei Ren,Na Zhao,Bo Han,Haifeng Chen,Gang Guo
Due to the hypoxic state of the tumor microenvironment (TME), photodynamic therapy (PDT) suffers from insufficient ROS production. The metal-polyphenol network-mediated Fenton reaction can generate reactive oxygen species (ROS) by consuming H 2 O 2 in TME, improving the inadequate ROS generation problem of PDT. Therefore, synergistic therapy combining PDT and Fenton response-based CDT is a promising approach for cancer treatment. Herein, a metal-polyphenol nanocomposite was deposited with gallic acid grafted hyaluronic acid and Fe 3+ to contrast a Ce6 nano-delivery system ( [email protected] NPs) for melanoma synergistic therapy. [email protected] NPs could be used as a Fenton reagent to induce the ·OH production and enhance the PDT effect of Ce6 to a certain extent. After 4 h of cellular uptake, the fluorescence intensity of Ce6 in the [email protected] NPs group was higher than 3 times that in the Ce6 group. The intracellular ROS generation level of the [email protected] NPs (L) group combining CDT and PDT was higher than that of the Ce6 group and [email protected] NPs group. In vitro and in vivo anti-melanoma studies show that [email protected] NPs (L) group exhibited better anti-melanoma than other groups. Together, [email protected] NPs provide a promising synergistic treatment potential for melanoma.
研究领域:
癌症治疗
·
纳米技术
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF MATERIALS SCIENCE
·
2023
·Vol. 58
·期 21
·8952-8968
·
IF 4.5
Qi Wenxia,Wang Shenglan,Yang Heng,Luo Tingting,Zhao Feng,Han Jingtian,Zhang Jing
Combination chemotherapy is a crucial therapeutic strategy to improve the therapeutic efficacy of breast cancer in clinic. When combined with photodynamic therapy (PDT), the therapeutic efficacy can be further enhanced not only by PDT-induced phototoxicity, but also by PDT-induced photochemical internalization which facilitates the intracellular delivery and endo/lysosomes escape of drugs, therefore exhibit considerable potential in clinical treatment of breast cancer. Herein, a novel cocktail therapeutic strategy based on albumin-based nanosystem was established by covalently modifying human serum albumin (HSA) with all-trans retinoic acid (RA) and chlorin e6 (Ce6) to form HSA-RA-Ce6 (HRC) conjugate, and using paclitaxel (PTX) to induce self-assembly of HRC to form HRC@PTX nanoparticles (HRC@PTX NPs). The HRC@PTX NPs could amplify the therapeutic efficacy of combination chemotherapy of RA and PTX with Ce6-mediated PDT. The HRC@PTX NPs were characterized with a mean particle size of 174.1 ± 2.1 nm and a slightly negative zeta potential and exhibited good stability and hemocompatibility. The HRC@PTX NPs could promote the cellular uptake of drugs by MCF-7 cells and MDA-MB-231 cells and produce ROS to amplify the synergistic anti-tumor efficacy. The in vitro inhibitory effects on tumor growth investigated on monolayer and three-dimensional tumor spheroids revealed that HRC@PTX NPs exhibited significantly higher anti-tumor activity when exposed to 660-nm laser. These results demonstrated that HRC@PTX NPs could be developed as a promising cocktail therapeutic strategy for synergistic breast cancer therapy. Graphical abstract
研究领域:
肿瘤学
·
药学
·
纳米技术
·
癌症治疗
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Luoyijun Xie,Li Wang,Ling Li,Chutong Liu,Lihao Guo,Yingying Liao,Shuyi Zhou,Weiwei Wu,Yanhong Duo,Leilei Shi,Miaomiao Yuan
Photosensitizers have been widely used to cause intratumoral generation of reactive oxygen species (ROS) for cancer therapy, but they are easily disturbed by the autophagy pathway, a self-protective mechanism by mitigating oxidative damage. Hereby, we reported a simple and effective strategy to construct a carrier-free nanodrug, Ce6@CQ namely, based on the self-assembly of the photosensitizer chlorin e6 (Ce6) and the autophagy inhibitor chloroquine (CQ). Specifically, Ce6@CQ avoided the unexpected toxicity caused by the regular nanocarrier and also ameliorated its stability in different conditions. Light-activated Ce6 generated cytotoxic ROS and elicited part of the immunogenic cell death (ICD). Moreover, CQ induced autophagy dysfunction, which hindered self-healing in tumor cells and enhanced photodynamic therapy (PDT) to exert a more potent killing effect and more efficient ICD. Also, Ce6@CQ could effectively accumulate in the xenograft breast tumor site in a mouse model through the enhanced permeability and retention (EPR) effect, and the growth of breast tumors was effectively inhibited by Ce6@CQ with light. Such a carrier-free nanodrug provided a new strategy to improve the efficacy of PDT via the suppression of autophagy to digest ROS-induced toxic substances.
研究领域:
肿瘤学
·
纳米技术
·
药学
·
免疫治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Yi Sun,Xin Peng,Yudong Guan,Tong Su,Zezun Xie,Ziying Wu,Yongxuan Long,Huihui Zhu,Jie Shao,Xiaoli Mai,Xuzhi Shi,Tingting Wu,Zhaogang Teng,Bing Zhang,Kun Chen,Xiaoyan Xin
Photodynamic Therapy (PDT) offers a promising minimally invasive treatment for breast cancer, but its efficacy is limited by the hostile tumor microenvironment (TME), including hypoxia and high glutathione (GSH) levels. Although various strategies to improve oxygen concentration or reduce reactive oxygen species (ROS) resistance for enhanced PDT have been explored, they typically require intricate design and complex synthesis of multifunctional nanocarriers. Thus, this study introduces a facile K 2 FeO 4 -induced strategy to enhance PDT efficiency in breast cancer through the tumor in situ synthesis of Fe 2 O 3 and O 2 . Inspired by the successful application of K 2 FeO 4 in ecological remediation and hemostasis, K 2 FeO 4 reacts with GSH, biological system, H 2 O 2 , and water, to generate Fe 2 O 3 and O 2 . Intratumoral injection of K 2 FeO 4 improves the TME, followed by Ce6 administration to enhance PDT through synergistic ferroptosis. This approach boosts PDT efficacy significantly by increasing ROS generation, lipid peroxidation, and inhibiting GSH and GPX4. Proteomic analysis revealed alterations in key pathways, including endocytosis and energy metabolism. This K 2 FeO 4 -PDT strategy creates a positive feedback loop by enhancing oxidative stress, providing an interesting and promising approach to PDT.
研究领域:
癌症研究
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2021
·
IF 13.273
Ting Su,Furong Cheng,Yuji Pu,Jun Cao,Shuibin Lin,Guizhi Zhu,Bin He
Cancer has been one of the major healthcare burdens, which demands innovative therapeutic strategies to improve the treatment outcomes. Combination therapy hold great potential to leverage multiple synergistic pathways to improve cancer treatment. Cancer cells often exhibit an increased generation of reactive oxygen species (ROS) and antioxidant species compared with normal cells, and the levels of these species can be further elevated by common therapeutic modalities such as photodynamic therapy (PDT) or chemotherapy. Taking advantage that cancer cells are vulnerable to further oxidative stress, we aim to design a drug delivery system by simultaneously increasing the cellular ROS level, reducing antioxidative capacity, and inducing anticancer chemotherapy in cancer cells. Here, we designed a star-shape polymer, PEG(- b -PCL-Ce6)- b -PBEMA, based on the Passerini three-component reaction, which can both enhance ROS generation during PDT and decrease the GSH level in cancer cells. The polycaprolactone conjugated with photosensitizer Ce6 served as hydrophobic segments to promote micelle formation, and Ce6 was used for PDT. The H 2 O 2 -labile group of arylboronic esters pendent on the third segment was designed for H 2 O 2 -induced quinone methide (QM) release for GSH depletion. We thoroughly investigated the spectral properties of blank micelle during its assembling process, ROS generation, and H 2 O 2 -induced QM release in vitro . Moreover, this polymeric micelle could successfully load hydrophobic anti-cancer drug Doxorubicin (DOX) and efficiently deliver DOX into cancer cells. The triple combination of ROS generation, GSH elimination, and chemotherapy dramatically improved antitumor efficiency relative to each of them alone in vitro and in vivo .
研究领域:
癌症治疗
·
纳米医学
·
药物递送系统
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2020
·
IF 10.317
Jie An,Yong-Guo Hu,Kai Cheng,Cheng Li,Xiao-Lin Hou,Gang-Lin Wang,Xiao-Shuai Zhang,Bo Liu,Yuan-Di Zhao,Ming-Zhen Zhang
Nanocarrier for augmenting the efficacy of reactive oxygen species (ROS) by tumor microenvironment (TME) has become an emerging strategy for cancer treatment. Herein, a smart biodegradable drug delivery nanoplatform with mitochondrial-targeted ability, pH-responsive drug release and enzyme-like catalytic function is designed. This efficient ROS-generating platform uses ultrasound with deeper penetration capability as excitation source for combined chemotherapy and sonodynamic therapy (SDT) of tumor. In vitro experiments show that the nanoplatform can co-load Ce6 and DOX and be degraded in slight acid environment, and the DOX release rate is 63.91 ± 1.67%. In vivo experiments show that the nanoplatform has extremely biosafety and can be enriched in tumor site and excluded from body after 24 h. More significantly, after combined treatment, the tumors are eliminated and the mice still survive healthily without recurrence after 60 d. This is because not only it can achieve mitochondrial targeting and use platinum particle to increase oxygen content in TME to enhance the effect of SDT, but also it can use weak acidic TME to accelerate drug release to achieve the combination of chemotherapy and SDT. The probe provides a new strategy for designing ROS-based nanoplatform for the treatment of malignant tumor.
研究领域:
纳米技术
·
癌症治疗
·
药物递送系统
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2018
·Vol. 10
·期 40
·19052-19063
·
IF 7.233
Yanlei Liu,Xiao Zhi,Wenxiu Hou,Fangfang Xia,Jingpu Zhang,Lexiang Li,Yuping Hong,Hao Yan,Chen Peng,Jesus Martinez de la Fuentea,Jie Song,Daxiang Cui
The development of multifunctional nanoparticles for tumor theranostics has become a research hotspot. Despite the advantages of non-invasive precision diagnostics and efficient drug-delivery, these nanoparticles bring two significant issues: (i) a potential toxic effect and (ii) difficult clearance. To solve these issues, carbon dots (C-dots) are key potential candidates owing to their unique properties, such as excellent biocompatibility and rapid renal clearance. However, their small size leads to a short circulation time in the blood, which causes non-sufficient tumor accumulation for antitumor therapy. To reach the balance between an efficient accumulation in a tumor and rapid clearance from the body, herein we report a new multifunctional nanoprobe: photosensitizer (chlorine e6, Ce6)-loaded assembled C-dots (A-C-dots@Ce6). The A-C-dots@Ce6 were assembled from negatively-charged discrete C-dots using Gd3+ ions as a “glue”. which also provided another function of in vivo nanoprobe monitoring via magnetic resonance (MR) imaging. Moreover, the nanoprobe exhibited an acidic pH-dependent disassembly and drug-release property. Benefiting from these advantages, the nanoprobe showed a targeted antitumor effect in A549 tumor-bearing mice under laser irradiation and gradual disassembly in the tumor for later body clearance. Therefore, the nanoprobe potentially provides a new strategy to solve the above balance issue, and brightens the future for antitumor monitoring and treatment.
研究领域:
纳米技术
·
生物医学工程
·
药学
·
材料科学
·
医学影像
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2021
·Vol. 31
·期 50
·2106106
·
IF 18.808
Jie Shen,Huizhu Yu,Yimeng Shu,Ming Ma,Hangrong Chen
The efficacy of cancer therapy with reactive oxygen species (ROS) as the main therapeutic medium suffers from a deficiency of oxy-substrates, for example, insufficient endogenous hydrogen peroxide (H 2 O 2 ) in chemodynamic therapy (CDT) and inherent hypoxia in photodynamic therapy (PDT). Herein, a smart polyethylene glycol (PEG)-ylated nanosystem CaO 2 @ZIF-Fe/Ce6@PEG (abbreviation as CaZFCP) is constructed to achieve H 2 O 2 /O 2 self-supply and Ca 2+ overloading in tumor cells simultaneously for enhanced CDT/PDT. Under the weakly acidic tumor microenvironment, the activity components inside CaZFCP, that is, CaO 2 nanoparticles, Fe 2+ , and photosensitizer Chlorin e6 (Ce6) are released by the degradation of zeolitic imidazole framework-90 (ZIF-90). Thereinto, CaO 2 nanoparticles are further decomposed to generate H 2 O 2 and O 2 , which alleviates both the insufficient endogenous H 2 O 2 and hypoxia in tumor area, thus enhancing the efficiency of CDT and PDT by producing more hydroxyl radicals and singlet oxygen. Furthermore, Ca 2+ overloading induced by the decomposition of CaO 2 is available for amplifying intracellular oxidative stress, resulting in mitochondrial dysfunction, which further improves the efficacy of combined CDT/PDT. In vitro and in vivo experimental results confirm excellent tumor inhibition effect, which also provides a facile paradigm in ROS-involved cancer therapies.
研究领域:
癌症治疗
·
纳米技术
·
生物医学工程
·
药学
✓ 已验证
DOI
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Yuping Zhao,Yanna Zhao,Qisan Ma,Bin Sun,Qingpeng Wang,Zhuang Ding,Huaizhen Zhang,Xiuling Chu,Min Liu,Zhengping Wang,Jun Han
Background The combination of chemo-photodynamic therapy based on nano-technology has emerged as a preferable and promising measure for synergetic antitumor therapy.Purpose The aim of this study was expected to overcome most of the safety concerns from nano-carriers and improve the chemo-photodynamic synergistic antitumor efficacy.Methods Herein, we reported a facile and effective approach based on the self-assembly of chemotherapeutic agent 10-hydroxycamptothecin (HCPT) and photosensitizer chlorin e6 (Ce6) for preparing stably dual-functional nanorods (NRs).Results The chemical thermodynamic parameters obtained from isothermal titration calorimeter (ITC) and the microcosmic configuration snapshots acquired by molecular dynamics (MD) simulations verified that HCPT and Ce6 molecules tended to assemble with each other through various intermolecular forces. The as-prepared HCPT/Ce6 NRs possessed a relatively uniform size of around 165 nm and zeta potential of about −29 mV, together with good stability in aqueous solution and freeze-dried state. In addition, both the extra- and intracellular reactive oxygen species (ROS) generation capacity of the NRs under laser irradiation was significantly enhanced compared with Ce6 injections. Moreover, the dual-functional HCPT/Ce6 NRs exhibited a substantial in vitro/in vivo synergistic antitumor efficacy under laser irradiation due to the integration of the two therapeutic modalities into one drug delivery system. Besides, no obvious hepatic or renal toxicity was observed in the NRs treatment groups.Conclusion Taken together, HCPT/Ce6 NRs demonstrated a powerful efficacy in chemo-photodynamic therapy for breast cancer. Therefore, the carrier-free dual-functional NRs prepared in a facile and effective strategy might give inspiration for the development of combined antitumor therapy.
研究领域:
纳米技术
·
药学
·
肿瘤学
·
材料科学
✓ 已验证
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2024
·
IF 9.4
Xingchen Li,Ming Hao,Annan Liu,Lei Li,Maja D. Nešić,Bai Yang,Weiwei Liu,Quan Lin
Oral squamous cell carcinoma (OSCC) is the most common malignant tumor in the head and neck region, and its treatment is limited by hypoxia and inadequate oxygen supply. Continuous oxygen delivery combined with photodynamic therapy (PDT) is the key to addressing this issue. Here, a dual-enzyme activity sea urchin-like Au@Pt-Ce6-HN-1 nanoplatform was designed to serve as an "oxygen pump" to alleviate tumor hypoxia for synergistic photodynamic/photothermal therapy (PTT). In this design, the photosensitizer chlorin e6 (Ce6) is covalently linked to the Au@Pt nanozyme for PDT treatment. The Au@Pt nanozyme exhibits catalase-like activity, continuously decomposing H 2 O 2 in the tumor microenvironment to enhance O 2 levels, thereby achieving efficient PDT. Furthermore, Au@Pt can perform PTT and increase oxygen levels under NIR-II light to further promote PDT. The Au@Pt nanozyme also exhibits peroxidase-like activity, generating ·OH for chemodynamic therapy (CDT). Additionally, HN-1 guides the direction of "sniping" OSCC, and its high specificity benefits Au@Pt-Ce6-HN-1 at the tumor site. Au@Pt-Ce6-HN-1 exhibits bright fluorescence (FL), strong CT signal, and photothermal imaging capabilities, laying the foundation for subsequent guided PDT/PTT. This nanoplatform, which combines advantages such as continuous oxygen production, tumor targeting, and multimodal imaging, is expected to provide valuable insights into the treatment of OSCC. Statement of Significance Accurate clinical diagnosis and treatment of OSCC are challenging. We report a dual-enzyme activity sea urchin-like Au@Pt-Ce6-HN-1 nanoplatform, serving as an "oxygen pump" to guide photodynamic therapy (PDT) and photothermal therapy (PTT) for OSCC. This nanoplatform targets OSCC for preoperative CT diagnosis and offers fluorescence visualization for surgical navigation, demonstrating potential in clinical cancer detection and surgery guidance. This innovative approach addresses OSCC hypoxia and enhances treatment efficacy through continuous oxygen production, tumor targeting, and multimodal imaging, significantly improving patient outcomes in OSCC treatment.
研究领域:
癌症治疗
·
纳米技术
·
光疗
·
医学成像
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Therapeutics
·
2023
·Vol. 6
·期 4
·2200237
·
IF 4.6
Yan-Mei Li,Xiang Zhou,Xin-Yu Li,Jia-Qi Huang,Zi-Wen Qiu,Ren-Jiang Kong,Ni Yan,Shi-Ying Li,Hong Cheng
Oxygen-dependent photodynamic therapy (PDT) holds unique advantages on tumor treatment by inducing cell apoptosis, but it is often limited owing to the unfavorable tumor microenvironments. In this study, a self-delivery O 2 -ecomonizer (designated as CeTam) is prepared to relieve hypoxia and reverse antiapoptotic pathway for enhanced photodynamic tumor therapy. Based on Chlorin e6 (Ce6) and Tamoxifen (Tam), CeTam is assembled through intermolecular hydrophobic interaction without any vehicles. Nanosized CeTam has an enhanced stability and improved drug delivery efficiency, which prefers to accumulate at tumor tissue for effective cellular uptake. More importantly, CeTam can effectively inhibit mitochondrial respiration to relieve hypoxia and reduce Bcl-2 expression to reverse antiapoptotic pathway. As a result, this self-delivery O 2 -ecomonizer successfully regulates the unfavorable tumor microenvironments to enhance the PDT efficacy on tumor elimination. Taken together, this work reports a multifunctional nanoplatform by a simple self-assembly strategy to remedy the deficiencies of PDT on hypoxic tumor treatment, which can advance the development of individualized biomedicine for precise tumor therapy.
研究领域:
癌症治疗
·
药理学
·
纳米技术
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）