INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2024
·
IF 5.3
Fengtian Zhang,Jiaoting Chen,Weihong Luo,Changlong Wen,Wei Mao,Yutian Yang,Chunting Liu,Youjia Xu,Weiliang Chen,Lijuan Wen
Clinical treatment for osteosarcoma (OS) is still lacking effective means, and no significant progress in OS treatment have been made in recent years. Single chemotherapy has serious side effects and can produce drug resistance easily, resulting poor therapeutic effect. As a modern and non-invasive treatment form, photodynamic therapy (PDT) is widely used to treat diverse cancers. Chemotherapy in combination with PDT is a particularly efficient antitumor method that could overcome the defects of monotherapies. Since mitochondria is a key subcellular organelle involved in cell apoptosis regulation, targeting tumor cells mitochondria for drug delivery has become an important entry point for anti-tumor therapy. Herein, we rationally designed a core-shell structured biomimetic nanoplatform, i.e., D@SLNP@OSM-IR780, to achieve tumor homologous targeting and mitochondria targeted drug release for chemotherapy combined with PDT against OS. Upon 808 nm laser irradiation, D@SLNP@OSM-IR780 exhibited excellent photo-cytotoxicity in vitro . The excellent targeting effect of D@SLNP@OSM-IR780 in tumor tissues produced a tumor inhibition rate of 98.9% in vivo . We further indicated that synergistic chemo-photodynamic effect induced by D@SLNP@OSM-IR780 could activate mitochondria-mediated apoptosis pathway, along with host immune response and potential photothermal effect. On the whole, D@SLNP@OSM-IR780 is revealed to be a promising platform for OS targeted combination therapeutics.
研究领域:
肿瘤学
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纳米技术
·
药学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Xinwei Fu,Shan Du,Jie Liang,Bo Wang,Yingqi Liu,Yunlong Yu,Liqun Xu,Peng Xue,Bin Wang,Yuejun Kang
Ion interference therapy (IIT) represents an intervention strategy aimed at modulating the intracellular distribution of functional ions to mitigate bacterial biofilm infections (BBI). However, bacteria tend to activate protective pathways to alleviate the damage induced by ion interference under stress conditions, substantially diminishing the long-term therapeutic efficacy of IIT. Herein, we proposed an antibiofilm strategy of the photodynamic therapy (PDT)-mediated hypoxia-enhanced copper ion interference therapy (PHCIIT). The double-layered microneedles (CuIA@SCC MN) were synthesized by integrating the novel copper-coordinated polymeric nanorods (CuIA NRs) with sodium copper chlorophyllin (SCC) on the surface of hydrogel microneedles. Compared to conventional copper ion therapy, treatment with CuIA@SCC MN resulted in the PDT-mediated hypoxic microenvironment, enhancing the copper toxicity by inhibiting the protective mechanisms of bacteria, including down-regulation of multicopper oxidase activity and the enhanced accumulation of monovalent copper ions. Furthermore, the sustained release of therapeutic copper ions from CuIA NRs within the micro-acidic biofilm would further aggravate copper overload. The efficacy of the PHCIIT strategy was validated using diabetic wounds infected with E. coli biofilm. Following PHCIIT intervention, macrophages in the infected tissues exhibited polarization towards the M2-like phenotype, which could expedite wound healing. It is believed that the PHCIIT-based strategy is highly significant in advancing conventional IIT.
研究领域:
生物医学工程
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微生物学
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材料科学
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治疗学
·
伤口愈合
✓ 已验证
DOI
高影响因子
ACS Omega
·
2019
·
IF 2.584
Jiang Ni,Ying Sun,Jinfang Song,Yiqing Zhao,Qiufang Gao,Xia Li
Recent studies have identified photodynamic therapy (PDT) as a promising approach for cancer treatment. Here, in this study, we have constructed cancer cell membrane (CCM)-coated silica nanoparticles (SIL) as an artificial cell carrier (CCM/SIL) to effectively deliver chlorin e6 (Ce6), a commonly adopted photodynamic reagent (CCM/SIL/Ce6), to achieve enhanced PDT of cancer. In addition, apart from the generally recognized cytotoxicity induced by reactive oxygen species (ROS), our study also revealed that ROS could further potentiate the loss of intercellular junctions and integrity disruption as a result of down-regulation of VE-cadherin and CD31. Consequently, dendritic cells (DCs) were more readily accumulated to the tumor tissue and became maturated, which secreted tumor necrosis factor-α and interleukin-12 (IL-12) to trigger the following immune responses. Our work not only explored the anticancer feasibility of a new system but also demonstrated the underlining mechanisms responsible for PDT-induced anticancer effects, which offers a new perspective to employ and improve the efficacy of PDT and related systems.
研究领域:
肿瘤学
·
纳米技术
·
免疫治疗
·
光动力疗法
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Shuxiang Xu,Shuyi Zhou,Luoyijun Xie,Wenlong Dou,Rongjun Zhang,Bingxia Zhao,Yang Xu,Xuemei Fu,Miaomiao Yuan
Due to the heterogeneous and complex tumor microenvironment (TME), it remains challenging to effectively treat solid tumors with monotherapy. The development of a versatile nanomaterial strategy for synergistic chemodynamic/photodynamic/photothermal therapies has the potential to overcome this challenge. Herein, we designed and synthesized NiS 2 /FeS 2 hybrid nanoparticles (NiS 2 /FeS 2 NPs), which are further modified with polyvinyl pyrrolidone (PVP) to improve their biocompatibility. PVP-NiS 2 /FeS 2 NPs exhibit synergistic activities of chemodynamic therapy (CDT), photodynamic therapy (PDT), and photothermal therapy (PTT) with multimodal imaging capabilities. With the presence of Fe 2+ /Fe 3+ and Ni 2+ /Ni 3+ redox couples, the PVP-NiS 2 /FeS 2 NPs exhibit GSH peroxidase-like reactivity and trigger Fenton reaction, leading to robust ·OH generation and pyroptosis/ferroptosis after near infared irradiation (NIR). In response to the PVP-NiS 2 /FeS 2 NPs and PVP-NiS 2 /FeS 2 NPs + NIR treatment, the breast tumors formed in the syngeneic BABL/c mice were eliminated and their metastases suppressed by inhibiting the EMT pathway. Consistent with the apparent involvement of these programmed cell death pathways in activating tumor immunity, we demonstrate that PVP-NiS 2 /FeS 2 NPs + NIR can eliminate metastatic tumors in an immune system dependent manner. Therefore, PVP-NiS 2 /FeS 2 NPs represent a promising strategy to treat metastatic breast cancer.
研究领域:
纳米技术
·
癌症治疗
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生物医学工程
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材料科学
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2021
·
IF 5.875
Shanshan Li,Kunpeng Lin,Peng Hu,Shaochen Wang,Shuang Zhao,Ying Gan,Lei Liu,Shuling Yu,Jiahua Shi
Phototherapies, including photothermal therapy (PTT) and photodynamic therapy (PDT) have been potential noninvasive therapeutic modality with high efficiency, however, there still exist some intrinsic limitations that impede their clinical applications. Herein, taking the advantages of the synergistic effect and high reactivity of manganese dioxide (MnO 2 ) nanosheets and glucose oxidase (GOx), multifunctional [email protected] 2 -MB-GOx nanoamplifier was constructed for enhanced PTT, PDT, and starvation therapy. In tumor microenvironment (TME), MnO 2 nanosheets on the surface of mesoporous polydopamine (MPDA) could react with endogenous hydrogen peroxide (H 2 O 2 ) and generate oxygen (O 2 ) to relieve tumor hypoxia, thus enhancing the efficacy of PDT and GOx catalysis. Glucose consumption under the catalysis of GOx will enhance the acidity of TME and increase intracellular H 2 O 2 concentration, which in turn promotes the production of O 2 by MnO 2 nanosheets, thus forming efficient cascade reaction and maximizing the efficacy of the functional agents. Furthermore, the heat generated by MPDA under the irradiation of 808 nm laser can accelerate chemical reactions, thus further enhancing synergistic therapeutic efficacy. In vitro/vivo results emphasize that enhanced cancer cell death and tumor inhibition are gained by modulating unfavorable TME with the functional nanosystem, which highlights the promise of the synthesized [email protected] 2 -MB-GOx nanomaterial to overcome the limitations of phototherapy.
研究领域:
纳米技术
·
癌症治疗
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生物医学工程
·
材料科学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2022
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IF 14.903
Zekun Li,Yongchun Pan,Shiyu Du,Yayao Li,Chao Chen,Hongxiu Song,Yueyao Wu,Xiaowei Luan,Qin Xu,Xiaoxiang Guan,Yujun Song,Xin Han
Near-infrared (NIR)-light-triggered nanomedicine, including photodynamic therapy (PDT) and photothermal therapy (PTT), is growing an attractive approach for cancer therapy due to its high spatiotemporal controllability and minimal invasion, but the tumor eradication is limited by the intrinsic anti-stress response of tumor cells. Herein, we fabricate a tumor-microenvironment responsive CRISPR nanoplatform based on oxygen-deficient titania (TiO 2- x ) for mild NIR-phototherapy. In tumor microenvironment, the overexpressed hyaluronidase (HAase) and glutathione (GSH) can readily destroy hyaluronic acid (HA) and disulfide bond and releases the Cas9/sgRNA from TiO 2- x to target the stress alleviating regulators, i.e. , nuclear factor E2-related factor 2 (NRF2) and heat shock protein 90 α (HSP90 α ), thereby reducing the stress tolerance of tumor cells. Under subsequent NIR light illumination, the TiO 2- x demonstrates a higher anticancer effect both in vitro and in vivo . This strategy not only provides a promising modality to kills cancer cells in a minimal side-effects manner by interrupting anti-stress pathways but also proposes a general approach to achieve controllable gene editing in tumor region without unwanted genetic mutation in normal environments.
研究领域:
癌症治疗
·
纳米技术
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基因编辑
·
光疗
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2021
·Vol. 17
·期 42
·2102527
·
IF 13.281
Yeneng Dai,Honghai Zhao,Kun He,Wenyu Du,Yingjie Kong,Zhen Wang,Meixing Li,Qingming Shen,Pengfei Sun,Quli Fan
The success of phototheranostics is hampered by some intrinsic defects, such as limited light penetration depth, heat resistance of tumor cells to photothermal therapy (PTT) induced by heat shock protein (HSP) and stress resistance against photodynamic therapy (PDT) caused by hypoxia microenvironment of tumor. Herein, a second near infrared (NIR-II) light excitation phototheranostic nanomedicine has been fabricated by integrating the semiconducting polymer, azo compound, and HSP inhibitor into a thermosensitive liposome, followed by modification with targeting aptamer, forming Lip(PTQ/GA/AIPH) for multimodal phototheranostics of triple-negative breast cancer (TNBC). The phototheranostic nanomedicine provides tumor targeting NIR-II fluorescence and photoacoustic dual-modal imaging, as well as NIR-II PTT. The released HSP inhibitor can effectively inhibit the activity of HSP for enhanced NIR-II PTT. Moreover, azo compound can be decomposed by the NIR-II photothermal activation, generating cytotoxic free radicals and realizing oxygen-irrelevant photonic thermodynamic therapy (PTDT) effects. Under the NIR-II laser irradiation, NIR-II fluorescence/photoacoustic dual-modal imaging guided enhanced NIR-II PTT and PTDT by Lip(PTQ/GA/AIPH), can achieve precise diagnosis and effective suppression of deep-seated TNBC with negligible side effects. This work develops a promising NIR-II excitation phototheranostic nanomedicine for spatiotemporally specific diagnosis and combination therapy of TNBC.
研究领域:
纳米技术
·
生物医学工程
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癌症研究
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诊疗学
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光学成像
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Gang Liu,Mingyu Liu,Xiujing Li,Xiaorong Ye,Kaiming Cao,Yangzhong Liu,Yue Yu
Reactive oxygen species (ROS) generation, using photodynamic therapy (PDT) and chemodynamic therapy (CDT), is a promising strategy for cancer treatment. However, the production of ROS in tumor cells is often limited by hypoxia, insufficient substrates, and high level of ROS scavengers in a tumor microenvironment, which seriously affects the efficacy of ROS-related tumor therapies. Herein, we report a lipid-supported manganese oxide nanozyme, MLP@DHA&Ce6, by decorating a MnO2 nano-shell on the liposome loaded with dihydroartemisinin (DHA) and photosensitizer Ce6 for generating multisource ROS to enhance cancer therapy. MLP@DHA&Ce6 can be accumulated in tumors and can release active components, Mn2+ ions, and O2. The conjugate generates ROS via nanozyme-catalyzed CDT using DHA as a substrate, PDT through Ce6, and the Fenton reaction catalyzed by Mn2+ ions. The production of O2 from MnO2 enhanced Ce6-mediated PDT under near-infrared light irradiation. Meanwhile, MLP@DHA&Ce6 showed prominent glutathione depletion, which allowed ROS to retain high activity in tumor cells. In addition, the release of Mn2+ ions and DHA in tumor cells induced ferroptosis. This multisource ROS generation and ferroptosis effect of MLP@DHA&Ce6 led to enhanced therapeutic effects in vivo.
研究领域:
癌症治疗
·
纳米技术
·
药学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2023
·
IF 9.9
Ran Hao,Gangwan Zhang,Jiahe Zhang,Leyong Zeng
The weak catalytic activity of nanocatalysts and the insufficient endogenous hydrogen peroxide (H 2 O 2 ) in tumor microenvironment (TME) seriously restricted the efficacy of catalytic therapy, and the non-degradability of inorganic nanocarriers was also unfavorable for their clinical applications. Herein, by depositing gold nanoparticles (AuNPs) and platinum nanoparticles (PtNPs) with ultrasmall size and modifying photosensitizer (IR808), a biocompatible bovine serum albumin (BSA) nanoplatform (BSA@Au/Pt-IR808) with triple-amplification of enzyme activity was constructed to enhance photodynamic therapy (PDT) and catalytic therapy. Ultrasmall AuNPs possessed glucose oxidase (GOx)-like activity, by which the self-supplying H 2 O 2 accelerated the dual-enzyme activity of peroxidase (POD) and catalase (CAT) of ultrasmall PtNPs, promoting the generation of hydroxyl radical (·OH) and singlet oxygen ( 1 O 2 ). Compared with BSA-IR808 and BSA@Pt, the yields of 1 O 2 and ·OH of BSA@Au/Pt-IR808 increased by 38.2% and 18.6%. Under the combination action of photothermal therapy (PTT)/PDT/catalytic therapy of BSA@Au/Pt-IR808, the cell viability significantly reduced to 12.8%, and the tumors were completely eliminated, demonstrating the enhanced PDT and catalytic therapy against breast cancer.
研究领域:
纳米技术
·
生物医学工程
·
癌症治疗
·
材料科学
·
光化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Yunsu Ma,Huanghuang Xu,Bo Sun,Silin Du,Shuai Cui,Li Zhang,Ning Ding,Dongzhi Yang
The combination of photodynamic therapy (PDT) and chemodynamic therapy (CDT) has been continuously explored in the antibacterial aspect and has achieved more effective antibacterial effect than a single therapy. We design a pH-responsive O2 and H2O2 self-supplying zeolitic imidazolate framework-67 (ZIF-67) nanosystem for PDT/CDT of wound infection. Under the acidic inflammatory conditions, ZIF-67 can degrade to produce Co2+ and release CaO2 and graphene quantum dots (GQDs). The exposed CaO2 reacted with water to generate H2O2 and O2. The self-supplied O2 alleviates hypoxia at the site of inflammation and enhances external light-initiated GQD-mediated PDT, while H2O2 was catalyzed by endogenous Co2+ to produce hydroxyl radicals for Co2+-triggered CDT. In vitro and in vivo experiments confirm that CaO2/GQDs@ZIF-67 has a combined PDT/CDT effect. The antibacterial mechanism indicates that bacteria post-treated with CaO2/GQDs@ZIF-67 may be sterilized by reactive oxygen species-mediated oxidative stress and the leakage of bacterial contents. The experiments also find that CaO2/GQDs@ZIF-67 may activate the immune response and enhance the therapeutic effect by activating the cyclic GMP–AMP synthase–stimulator of interferon genes signaling pathway.
研究领域:
纳米技术
·
生物医学工程
·
药学
·
传染病
·
材料科学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2024
·
IF 9.4
Li Tu,Shengqiang Chen,Zhikang Yuan,Yeqi Xiong,Bingkun Luo,Ying Chen,Zhenqing Hou,Sunkui Ke,Naibo Lin,Chao Li,Shefang Ye
Nanozymes, as nanomaterials with natural enzyme activities, have been widely applied to deliver various therapeutic agents to synergistically combat the progression of malignant tumors. However, currently common inorganic nanozyme-based drug delivery systems still face challenges such as suboptimal biosafety, inadequate stability, and inferior tumor selectivity. Herein, a super-stable amino acid-based metallo-supramolecular nanoassembly (FPIC NPs) with peroxidase (POD)- and glutathione oxidase (GSHOx)-like activities was fabricated via Pt 4+ -driven coordination co-assembly of l -cysteine derivatives, the chemotherapeutic drug curcumin (Cur), and the photosensitizer indocyanine green (ICG). The superior POD- and GSHOx-like activities could not only catalyze the decomposition of endogenous hydrogen peroxide into massive hydroxyl radicals, but also deplete the overproduced glutathione (GSH) in cancer cells to weaken intracellular antioxidant defenses. Meanwhile, FPIC NPs would undergo degradation in response to GSH to specifically release Cur, causing efficient mitochondrial damage. In addition, FPIC NPs intrinsically enable fluorescence/photoacoustic imaging to visualize tumor accumulation of encapsulated ICG in real time, thereby determining an appropriate treatment time point for tumoricidal photothermal (PTT)/photodynamic therapy (PDT). In vitro and in vivo findings demonstrated the quadruple orchestration of catalytic therapy, chemotherapeutics, PTT, and PDT offers conspicuous antineoplastic effects with minimal side reactions. This work may provide novel ideas for designing supramolecular nanoassemblies with multiple enzymatic activities and therapeutic functions, allowing for wider applications of nanozymes and nanoassemblies in biomedicine.
研究领域:
纳米技术
·
癌症治疗
·
生物医学工程
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Yuxuan Wei,Zuxiao Chen,Chuyu Huang,Hong Cheng,Xiaofeng Jiang,Shiying Li
Spatiotemporal downregulation of immune checkpoint provides a promising strategy to activate anti-tumor immunity. In this work, a breast cancer targeted photodynamic degrader (designated as EIpro) is constructed to activate immunotherapy through EGFR degradation mediated PD-L1 downregulation. To be specific, we develop a chimeric peptide, comprising the photosensitizer Protoporphyrin IX (PpIX) and EGFR targeting peptide (QRHKPRE), to encapsulate an EGFR inhibitor afatinib (AFA) forming nanomicelle, namely EIpro. EIpro has a favorable stability and uniform nanosize distribution, preferring to accumulate in EGFR overexpressed breast cancer cells to amplify the chemotherapeutic effect and photodynamic elimination behavior. More interestingly, photodynamic therapy (PDT) produced reactive oxygen species (ROS) is able to damage breast cancer cells and induce immunogenic cell death (ICD) to release tumor associated antigens (TAAs), thereby degrading the nearby EGFR to downregulate PD-L1 and activate anti-tumor immunity. Beneficially, the multi-synergistic effects of EIpro show a robust therapeutic efficacy against primary and metastatic breast cancer with negligible systemic toxicity. This work provides a spatiotemporal strategy for protein degradation, which might inspire the development of sophisticated nanomedicine for effective tumor treatment.
研究领域:
肿瘤学
·
免疫治疗
·
纳米医学
·
光动力疗法
·
癌症生物学
✓ 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）