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JOURNAL OF CONTROLLED RELEASE · 2017 · IF 7.786

Overcoming photodynamic resistance and tumor targeting dual-therapy mediated by indocyanine green conjugated gold nanospheres

Wei Li,Xiaomeng Guo,Fenfen Kong,Hanbo Zhang,Lihua Luo,Qingpo Li,Chunqi Zhu,Jie Yang,Yongzhong Du,Jian You

Photodynamic therapy (PDT) and photothermal therapy (PTT) have captured much attention due to the great potential to cure malignant tumor. Nevertheless, photodynamic resistance of cancer cells has limited the further efficacy of PDT. Unfortunately, the resistance mechanism and efforts to overcome the resistance still have been rarely reported so far. Here, we report a nanosystem with specific tumor targeting for combined PDT and PTT mediated by near-infrared (NIR) light, which was established by covalently conjugating indocyanine green (ICG) and TNYL peptide onto the surface of hollow gold nanospheres (HAuNS). Our nanosystem (TNYL-ICG-HAuNS) was proved to possess significantly increased light stability, reactive oxygen species (ROS) production and photothermal effect under NIR light irradiation, thus presenting a remarkably enhanced antitumor efficacy. The up-regulation of nuclear factor erythroid 2-related factor 2 (NFE2L2, Nrf2) in cancer cells during PDT induced a significant increase of ABCG2 , NQO-1 and HIF-1α expression, causing PDT resistance of the cells. Interestingly, ABCG2 expression could almost keep a normal level in the whole PDT process mediated by TNYL-ICG-HAuNS. After repeated irradiations, TNYL-ICG-HAuNS could still produce almost constant ROS in cells while the Nrf2 expression reduced significantly. Furthermore, PDT resistance induced an obvious decrease of the internalization of free ICG, but didn't influence the cell uptake of TNYL-ICG-HAuNS. Our data explained that TNYL-ICG-HAuNS could overcome the photodynamic resistance of cancer cells, acting as a promising modality for simultaneous photothermal and photodynamic cancer therapy.

CAS / MDL: 1122-58-3
研究领域: 癌症治疗 · 纳米技术 · 生物医学工程 · 分子生物学
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Biomaterials Science · 2021 ·Vol. 9 ·期 20 ·6830-6841 · IF 6.843

Transdermal delivery of multifunctional CaO2@Mn-PDA nanoformulations by microneedles for NIR-induced synergistic therapy against skin melanoma

Liming Ruan,Gao Song,Xueya Zhang,Tianqi Liu,Yanfang Sun,Junlan Zhu,Zhiyong Zeng,Guohua Jiang

The development of multifunctional nanoformulations (NFs) include several features in a single nanosystem for these devices to overcome the disadvantages of inefficiency and undesirable toxicity of traditional therapies and provide new opportunities in the management of tumors. Herein, multifunctional CaO2@Mn-PDA NFs with a core–shell structure, integrating the photothermal conversion properties of Mn-PDA, the chemodynamic properties of doped Mn ions, and relieving hypoxia in the tumor microenvironment (TME) were developed. The as-fabricated CaO2@Mn-PDA NFs were embedded in microneedles (MNs) for transdermal delivery into tumor sites, leading to the generation of a new minimally invasive and synergistic therapeutic strategy against skin melanoma. Under near-infrared (NIR) light irradiation, the CaO2@Mn-PDA NFs exhibited a synergistic therapeutic effect, including photothermal therapy (PTT), chemodynamic therapy (CDT), and modulating hypoxia due to their high photothermal conversion efficiency, boosted intracellular production of reactive oxygen species, excellent chemodynamic reactions, etc. Therefore, the developed MN platform, which can build implanted multifunctional characteristics for on-demand NIR-induced synergistic therapy, have a bright future in tumor suppression.

研究领域: 生物医学工程 · 纳米技术 · 癌症治疗 · 药学
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Advanced Healthcare Materials · 2023 ·Vol. 12 ·期 11 ·2202817 · IF 10

Phototheranostic Agents Based on Nonionic Heptamethine Cyanine for Realizing Synergistic Cancer Phototherapy

Tianguang Liu,Yanli Chen,Huizhe Wang,Mengyuan Cui,Jiaqi Zhang,Wancun Zhang,Peng Wang

Asymmetrical heptamethine cyanine with near-infrared (NIR) absorption is used for photothermal therapy (PTT) of cancer. Aiming to overcome the drawbacks caused by the high temperature of PTT, the development of asymmetrical heptamethine cyanine with photothermal and photodynamic properties is still an attractive strategy. Different from the traditional method of the heavy atom effect, in this work, the carboxyl or sulfonic groups are introduced into the indole ring or branch chain of asymmetrical heptamethine cyanine to afford a series of new phototherapy agents. After being encapsulated by DSPE-PEG 2000 , BSS-Et NPs exhibit robust photostability, efficient reactive oxygen species generation (49%), and excellent photothermal conversion efficiency of about 37.6% under 808 nm laser irradiation. BSS-Et NPs possess passive tumor-targeting properties in vivo to not only visualize the tumor by NIR fluorescence imaging but also eliminate the tumor without any recurrence by photodynamic therapy and PTT synergistic therapy under laser irradiation. In addition, benefitting from the characteristics of organic small molecules, they can be metabolized quickly through the liver without inducing toxicity in the whole body. In general, this study provides a new direction for the development of multifunctional phototherapy agents for cancer treatment.

CAS / MDL: 298-93-1
研究领域: 癌症治疗 · 药物化学 · 生物医学工程 · 材料科学
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EUROPEAN POLYMER JOURNAL · 2023 · IF 6

Photothermal nanoagent for anti-inflammation through macrophage repolarization following antibacterial therapy

Yueying Xu,Yanjun Cai,Yu Xia,Quanxin Wu,Mingen Li,Ning Guo,Yingfeng Tu,Bin Yang,Yun Liu

Owing to the ignorable bacterial resistance, photothermal therapy (PTT) has been widely studied for bacterial infection. However, few research efforts have focused primarily on the simultaneous utilization of photothermal agents (PTAs) for anti-inflammatory therapy following PTT. Here, we developed a nano-sized PTA ( [email protected] ) through the self-assembly of Fe 3+ and epigallocatechin-3-gallate (EGCG) by using BSA as the nanoreactor and colloidal stabilizer. Next, we assessed its photothermal and reactive oxygen species (ROS) scavenging properties. In addition, we evaluated its antibacterial and anti-inflammatory abilities through in vitro antibacterial and cellular assays, respectively. Finally, we tested its in vivo sterilization and anti-inflammatory effects. Firstly, [email protected] displayed good photothermal capacity due to the inherent photothermal ability of metal-phenolic networks (MPNs). Consequently, [email protected] showed excellent both in vitro and in vivo antibacterial capacities. Moreover, [email protected] exhibited outstanding anti-oxidative property owing to ROS scavenging effect of EGCG. As a result, it presented extraordinary both in vitro and in vivo anti-inflammatory efficiencies through promoting the repolarization of pro-inflammatory (M1) macrophages to anti-inflammatory (M2) macrophages with the released EGCG. The research findings indicated that the prepared nanoagent has great potential to be used for combined antibacterial and anti-inflammatory treatments in future clinical applications.

研究领域: 纳米技术 · 药理学 · 生物医学工程 · 传染病学 · 免疫学
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Acta Biomaterialia · 2024 · IF 9.4

Dual-activity nanozyme as an oxygen pump to alleviate tumor hypoxia and enhance photodynamic/ NIR-II photothermal therapy for sniping oral squamous cell carcinoma

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
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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS · 2024 · IF 4.9

Cu(II)-doped mesoporous polydopamine as biodegradable nanoplatforms for photothermal-enhanced multi-mode anti-tumor therapy

Ziwei Yan,Hui Zhang,Jinghao Chen,Qingqing Xu,Shuaipeng Feng,Qinfu Zhao,Siling Wang

Photothermal effect produced in photothermal therapy (PTT) can not only eradicate tumors but also allow the promotion of biological and chemical reactions in tumor tissues, leading to the potential of photothermal-enhanced anti-tumor therapy with desirable outcomes. Biodegradable polydopamine (PDA) nanoparticles exhibit remarkable photothermal conversion efficiency and stability, making them ideal photothermal agents (PTAs) to achieve photothermal-enhanced anti-tumor therapy. The high affinity of PDA to metal ions provides a broad application prospect for the development of multi-functional nanoplatforms to achieve cancer therapy with high efficacy and specificity. In this work, we fabricated Cu(II)-doped mesoporous PDA nanoparticles with polyethylene glycol (PEG) modified (CMP-P), which not only possessed higher photothermal conversion efficacy than mesoporous PDA nanoparticles , but also presented distinctive self-enhanced chemodynamic (CDT) performance. CMP-P mediated CDT was predicated on catalyzing the Fenton-like reaction to generate hydroxyl radicals (·OH). Impressively, CMP-P further triggered glutathione (GSH) depletion intracellular to prevent the consumption of ·OH, and the photothermal effect further improved ·OH generation. Meanwhile, CMP-P exhibited favorable degradability, the process of which was elaborated intuitively by transmission electron microscope (TEM). CMP-P was then employed for doxorubicin (DOX) loading, and enabled the enhanced DOX release in-situ under the stimulation of photothermal effect and tumor micro-environment (TME). The lower IC 50 value of DOX/CMP-P (1.68 μg/mL) than the signal therapy suggested the superior synergistic effect of DOX/CMP-P. Meanwhile, in vivo experiments also revealed the considerably improved anti-tumor efficacy of synergistic therapy mediated by DOX/CMP-P.

研究领域: 生物医学工程 · 纳米医学 · 癌症治疗 · 材料科学
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Materials Today Chemistry · 2024 · IF 6.7

Ti3C2Tx MXene quantum dots coated hollow manganese dioxide nanoparticles for tumor combination therapy and magnetic resonance imaging

Linwei Li,Zihan Xing,Tao Liao,Jinyu Wang,Ziqiang Xu,Ying Kuang,Cao Li

Chemodynamic therapy (CDT) is a new cancer treatment that uses low-valence transition metal ions to catalyze intracellular Fenton/Fenton-like reactions, producing hydroxyl radicals (•OH) to eliminate cancer cells. However, achieving satisfactory therapeutic outcomes with CDT alone can be challenging. In this work, we reported an anticancer drug delivery DOX@HMDN-TQDs@PEI-PEG (DMTP) based on hollow mesoporous manganese dioxide nanoparticle (HMDN), which has the potential to improve cancer therapy by combining synergistic therapeutic and tumor magnetic resonance imaging (MRI) capability. After loading the anticancer drug doxorubicin hydrochloride (DOX), the pores of HMDN were sealed with polyethyleneimine (PEI) modified Ti 3 C 2 T x MXene quantum dots (TQDs) and finally modified with polyethylene glycol (PEG) to obtain the final system. HMDN depletes glutathione (GSH), which is harmful to CDT, in cancer cells, and generates Mn 2+ that can be used for both CDT and MRI. TQDs can also be used for highly effective photothermal therapy (PTT) that enhances CDT. The combination of DOX with chemotherapy can significantly inhibit tumor growth. In addition, DMTP combines the capability of tumor MRI as Mn 2+ is also a T 1 -weighted contrast agent . This multifunctional delivery system provides new ideas for research related to tumor diagnosis and treatment.

CAS / MDL: 25316-40-9
研究领域: 生物医学工程 · 纳米医学 · 癌症治疗 · 分子影像
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ACS Applied Materials & Interfaces · 2019 · IF 8.456

Development of Multifunctional Clay-Based Nanomedicine for Elimination of Primary Invasive Breast Cancer and Prevention of Its Lung Metastasis and Distant Inoculation

Ling-xiao Zhang,Xia-mei Sun,Zhi Ping Xu,Rui-tian Liu

Cancer recurrence and metastasis are worldwide challenges but current bimodular strategies such as combined radiotherapy and chemotherapy (CTX), and photothermal therapy (PTT) and immunotherapy have succeeded only in some limited cases. Thus in the present study, a multifunctional nanomedicine has been rationally designed via elegantly integrating three FDA-approved therapeutics, that is, indocyanine green (for PTT), doxorubicin (for CTX), and CpG (for immunotherapy) into the structure of layered double hydroxide (LDH) nanoparticles, aiming to completely prevent the recurrence and metastasis of invasive breast cancer. This multifunctional hybrid nanomedicine has been demonstrated to eliminate the primary tumor and efficiently prevent tumor recurrence and lung metastasis through combined PTT/CTX and induction of specific and strong immune responses mediated by the hybrid nanomedicine in a 4T1 breast cancer mouse model. Furthermore, the promoted in situ immunity has significantly inhibited the growth of reinoculated distant tumors. Altogether, our multifunctional LDH-based nanomedicine has showed an excellent efficacy in invasive cancer treatment using much lower doses of three FDA-approved therapeutics, providing a preclinical/clinical alternative to cost-effectively treat invasive breast cancer.

研究领域: 肿瘤学 · 纳米医学 · 免疫疗法 · 药学科学 · 生物医学工程
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JOURNAL OF CONTROLLED RELEASE · 2023 · IF 10.8

Pyroelectric Janus nanomotors to promote cell internalization and synergistic tumor therapy

Jie Meng,Kun Wei,Shuang Xie,Zhanlin Zhang,Pan Ran,Peng Zhang,Xiaohong Li

The tumor diffusion and cell internalization are the major obstacles to improving delivery efficacy of therapeutic agents. External electric fields have shown strong effect on the cell membrane polarization and fluidity, but usually need complicated power management circuits. Herein, in situ generation of microelectric field on nanoparticles (NPs) is proposed to overcome these delivery barriers. Janus [email protected] NPs were developed through partially coating of polydopamine (PDA) caps on pyroelectric tetragonal BaTiO 3 (tBT) NPs and then camptothecin (CPT) conjugation via disulfide linkages. For comparison, [email protected] NPs were prepared from non-pyroelectric cubic BaTiO 3 (cBT) as control. Near-infrared (NIR) illumination on PDA caps of the Janus NPs produces asymmetric thermophoretic force to drive NP motion for tumor accumulation, deep tissue penetration and effective cell interaction. Photothermally created temperature variations on tBT NPs build pyroelectric potentials to selectively change the membrane potential of tumor cells other than normal cells and exhibit a dominated role in enhancing tumor cell internalization and cytotoxicity. The combination index analysis confirms the synergistic effect of pyroelectric dynamic therapy (PEDT), chemotherapy and photothermal therapy (PTT), leading to full inhibition of tumor growth and noticeable extension of animal survival at significant lower CPT doses. The mild PTT/PEDT, the reduced CPT dose and the selective toxicity to tumor cells have achieved favorable treatment safety after [email protected] /NIR treatment. Therefore, in response to the differences in membrane potentials and glutathione levels between tumor and normal cells, we have demonstrated a concise design to achieve thermophoresis-driven motion, pyroelectric potential-enhanced cell internalization and PTT/PEDT/chemotherapy-synergized antitumor treatment.

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

CuO2-assisting-Zn single atom hybrid nanozymes for biofilm-infected wound healing

Junyao Song,Haoyu Chen,Yaqian Lv,Wanqun Yang,Fenglang Zhang,Tianyi Wang,Danping Liu,Yingshan Qu,Lei Han,Jun Fu,Xiaoying Kong

Single-atom catalysts (SACs), characterized by atomically dispersed single metal atoms, provide superior antibacterial properties over common nanozyme materials due to their satisfactory catalytic activity. However, when used for the treatment of biofilm-infected wounds, SACs are still unable to effectively solve severe microbial infection due to the insufficient supply of reactive oxygen species (ROS). Herein, a new hybrid nanozymes consisting of Zn single-atom catalysts and copper peroxide (Zn SACs@CuO 2 ) were prepared to realize the upgrading of ROS generation and the combination of photothermal/chemodynamic (PTT/CDT) therapy for biofilm-infected wound. Specifically, CuO 2 exhibited not only excellent photothermal property, but also H 2 O 2 -producing and Fenton-like catalytic activities, which assisted Zn SACs to accelerate the ·OH conversion of endogenous and exogenous H 2 O 2 . Compared with single antimicrobial strategies of Zn SACs, Zn SACs@CuO 2 hybrid nanozymes exhibited stronger therapeutic effects of biofilm destruction, immune activation and inflammation improvement. In conclusion, this work developed a hybrid single atom nanozyme material with for efficient biofilm-infected wound healing.

研究领域: 纳米技术 · 材料科学 · 生物医学工程 · 伤口愈合 · 抗菌治疗
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Biomaterials Science · 2023 ·Vol. 11 ·期 14 ·4874-4889 · IF 6.6

Hollow silver–gold alloy nanoparticles for enhanced photothermal/photodynamic synergetic therapy against bacterial infection and acceleration of wound healing

Shanshan Lin,Hui Chen,Rui Wang,Tongmeng Jiang,Rui Wang,Fabiao Yu

Bacterial infection seriously restricts the wound healing process due to severe inflammation and delayed wound healing. Unfortunately, the overuse or improper use of antibiotics leads to the advent of multidrug-resistant strains and intractable biofilms, severely affecting the therapeutic effect. Therefore, there is an urgent need to develop antibiotic-free strategies to accelerate the healing process of wounds with bacterial infection. Considering that single photothermal therapy (PTT) or photodynamic therapy (PDT) cannot fully meet the requirements of clinical sterilization and accelerating wound healing, herein, hollow silver–gold alloy nanoparticles immobilized with the photosensitizer molecule Ce6 (Ag@Au-Ce6 NPs) integrated with PTT and PDT are proposed for killing bacteria and accelerating wound healing. The photothermal conversion properties of Ag@Au-Ce6 NPs are obtained using an infrared thermal imager, and the generation of singlet oxygen (1O2) is verified with an 1O2 fluorescent probe DCFH-DA. Manipulated by near-infrared laser triggered mild hyperthermia and limited ROS amount, Ag@Au-Ce6 NPs could effectively kill bacteria that are free and colonized on the surface of wounded skin, promoting epithelium migration and vascularization, further accelerating wound healing, which showed great promise for biomedical application.

研究领域: 纳米技术 · 生物医学工程 · 光疗 · 伤口愈合 · 抗菌治疗
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Advanced Healthcare Materials · 2023 · IF 10

Stimulus-Detonated Biomimetic “Nanobomb” with Controlled Release of HSP90 Inhibitor to Disrupt Mitochondrial Function for Synergistic Gas and Photothermal Therapy

Geng Yang,Ting Song,Hanxi Zhang,Mengyue Li,Xiaodan Wei,Wanyi Zhou,Chunhui Wu,Yiyao Liu,Hong Yang

Photothermal therapy (PTT) is considered a promising treatment for tumors; however, its efficacy is restricted by heat shock proteins (HSPs). Herein, a stimuli-responsive theranostic nanoplatform (M/D@P/E-P) is designed for synergistic gas therapy and PTT. This nanoplatform is fabricated by a load of manganese carbonyl (MnCO, CO donor) in dendritic mesoporous silicon (DMS), followed by the coating with polydopamine (PDA) and loading of epigallocatechin gallate (EGCG, HSP90 inhibitor). Upon near-infrared (NIR) irradiation, the photothermal effect of PDA can kill tumor cells and allow for the controlled drug release of MnCO and EGCG. Moreover, the acidity and H 2 O 2 -rich tumor microenvironment enable the decomposition of the released MnCO, accompanied by the production of CO. CO-initiated gas therapy can realize to disrupt the mitochondrial function, which will accelerate cell apoptosis and down-regulate HSP90 expression by decreasing intracellular ATP. The combination of EGCG and MnCO can significantly minimize the thermo-resistance of tumors and improve PTT sensitivity. In addition, the released Mn 2+ enables T 1 -weighted magnetic imaging of tumors. The therapeutic efficacy of the nanoplatform is methodically appraised and validated both in vitro and in vivo. Taken together, this study affords a prime paradigm for applying this strategy for enhanced PTT via mitochondrial dysfunction.

研究领域: 癌症治疗 · 材料科学 · 生物医学工程 · 纳米医学
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