JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2017
·
IF 4.233
Haijie Han,Jinhui Wang,Tingting Chen,Lichen Yin,Qiao Jin,Jian Ji
Development of gemcitabine (GEM) nanocarriers as theranostic agents for pancreatic cancer chemotherapy has received extensive attention in recent years. A novel enzyme-sensitive albumin-based GEM delivery nanoplatform was developed in this research by simple conjugation of GEM to human serum albumin (HSA) via cathepsin B cleavable peptide GFLG and then complexing with near-infrared (NIR) dye IR780, forming a HSA-GEM/IR780 complex. The successful preparation of HSA-GEM/IR780 complex was confirmed by Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS), UV–vis–NIR absorption spectra and fluorescent emission spectra . The in vivo performance of HSA-GEM/IR780 complex was carried out on BxPC-3 pancreatic tumor xenografted mice. As revealed by in vivo NIR imaging, HSA-GEM/IR780 exhibited enhanced accumulation and long-term retention in tumor tissues compared to free IR780. Meanwhile, compared to free GEM, the deamination of GEM nanovectors into inactive 2′,2′-difluorodeoxyuridine (dFdU) can be greatly suppressed, while the concentration of the activated form of GEM (gemcitabine triphosphate, dFdCTP) was significantly increased in tumor tissue, thus exhibiting superior tumor inhibition activity with minimal side effects.
研究领域:
药学
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纳米技术
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肿瘤学
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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
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2024
·
IF 9.4
Yuanqi Yang,Qingqing Xu,Wei Gu,Kaisheng Nan,Siyu Chen,Siling Wang,Jinghai Zhang,Qinfu Zhao
Photodynamic therapy (PDT) has witnessed remarkable progress in recent years owing to its specific properties. Given that the antioxidation system of tumor microenvironment (TME) adversely affects treatment outcomes, powerful TME modulators can significantly resolve the limitation of PDT. Herein, we developed a PEG-modified Cu 2+ -doped hollow mesoporous carbon nanozyme (CHC-PEG) and loaded insoluble photosensitizer IR780 into its pores and cavities to construct the multifunctional nano-system IR780/CHCP. CHC-PEG nanozyme could perform photothermal therapy (PTT) effect and protect IR780 from aggregation-caused quenching (ACQ) effect, while exerting peroxidase (POD)-mimetic activity and the ability of consuming glutathione (GSH) to achieve oxidative stress-augmented PDT effect. When exposed to near-infrared (NIR) light, IR780 was stimulated to produce singlet oxygen ( 1 O 2 ) and CHC-PEG could increase the temperature of TME to exert stronger POD-mimetic activity for producing more hydroxyl radicals ( OH), therefore the IR780/CHCP nano-system exhibited remarkable tumor growth inhibition. Benefited by the enhanced synergistic effect, IR780/CHCP exhibited remarkable in vivo tumor growth inhibition, with the tumor inhibition rate of 93 %, and had no significant effect on major organs. Above all, IR780/CHCP could resist the antioxidant system in TME to enhance the level of oxidative stress, thereby enabling effective anti-tumor therapy. This study introduced a novel strategy to effectively promote the synergistic PTT/PDT effect by the enhanced oxidative stress.
研究领域:
癌症治疗
·
纳米医学
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材料科学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Research Express
·
2021
·Vol. 8
·期 4
·045017
·
IF 1.62
Guanchen Zhu,Qingfeng Zhang,Xiaozhi Zhao,Qing Zhang,Wei Chen,Linfeng Xu,Sheng Zhao,Kaikai Wang,Tianqing Liu,Hongqian Guo
Bladder cancer (BC) is one of the commonest malignancies in the urinary system. Bladder cancer is divided into non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC) according to the depth of invasion. Besides, the prognosis of MIBC remains poor. Surgical resection combined with radiotherapy or chemotherapy is the standard treatment for MIBC. However, the major obstacle that hinders successful chemotherapy is its lack of tumor targeting. Here, we fabricated nanoparticles that respond to near-infrared laser irradiation in order to increase the drug accumulation at the tumor sites and combine chemotherapy with photothermal therapy to overcome challenges of bladder cancer treatment. IR780 and Doxorubicin (DOX) were loaded into albumin nanoparticles (IR780-DOX@Albumin NPs). In the process of IR780-DOX@Albumin NPs synthesis, the near-infrared molecule IR780 was used as the assembly molecular bridge. Under irradiation, the nanoparticles were decomposed due to the degradation of IR780 while the release of DOX increased. Nanoparticles can be ingested by tumor cells in a short time. The IR780-DOX@Albumin NPs were sensitive to near-infrared laser irradiation. Near-infrared laser irradiation can promote the release of the drugs from the nanoparticles and induce a photothermal effect, thus destroying the tumor cells. Given the excellent tumor-targeting ability and negligible toxicity to normal tissue, IR780-DOX@Albumin NPs can greatly increase the concentration of chemotherapeutic drugs in tumor cells. This study combines photothermal therapy and chemotherapy to treat MIBC, so as to avoid chemotherapy resistance, reduce the toxicity to normal cells, and achieve the purpose of improving the treatment of MIBC.
研究领域:
癌症治疗
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纳米医学
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生物医学工程
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药学
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Mengmeng Dong,Yumeng Liu,Yuting Xiao,Qingqing Wu,Mingjing Guan,Zunqiang Xiao,Junwei Liu,Lidong Cao,Yi Lu
Hepatocellular carcinoma (HCC) is one of the most prevalent and aggressive forms of liver cancer, with limited therapeutic options and a high recurrence rate. Traditional treatments include surgery and systemic therapy, but systemic therapy has side effects, such as poor specificity, systemic toxicity, and drug resistance. Herein, we designed a multimodal diagnostic and therapeutic-integrated nanosphere for packaging and delivering lenvatinib (LVN). The system was constructed using a PLGA-PEG polymer and modified by cyclic peptide cRGD with high selectivity and affinity for cancer cell integrins. Next, the system was loaded with lenvatinib (LVN) and IR780 photosensitizer, providing a satisfactory basis for photodynamic therapy/photothermal therapy (PDT/PTT) treatment. The nanoparticles could actively and passively target HCC cells and hydrolyze them in an acidic environment to release photosensitizers and LVN, which played significant roles in diminishing tumor cells. After 808 nm laser irradiation, the PDT and PTT effects induced by IR780 synergistically increased the function of LVN by inducing ferroptosis and apoptosis. In addition, in vivo and in vitro experiments showed that PPR@LVN/IR780 nanoparticles could inhibit the growth of tumors under 808 nm laser irradiation without obvious damage to other organs. At the same time, we also used high-throughput sequencing technology to further explore the underlying mechanisms of the nanoparticles. This work not only provided a liver-targeted drug delivery strategy based on first-line systemic therapy drugs but also provided an efficient and synergistic visualization imaging method for fluorescence imaging (FLI), photoacoustic imaging (PAI), and photothermal imaging (PTI) to realize integrated multimodal diagnosis and treatment.
研究领域:
纳米医学
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肿瘤学
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药物递送系统
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光动力疗法
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光热疗法
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分子成像
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·
IF 10.6
Wenjie Xu,Zhaokui Zeng,Yucheng Tang,Jingjing Tian,Xinyan Hao,Pengcheng Sun,Yanjin Peng,Tian Tian,Daxiong Xiang,Rongrong Wang,Chuanpin Chen,Junyong Wu
Chemotherapy is still one of the major approaches in triple-negative breast cancer (TNBC) treatment. The development of new formulations for classic chemotherapeutic drugs remains interests in studies. Camptothecin (CPT) is powerful antitumor agents in TNBC treatment though its clinic applications are limited by its low water solubility and systemic toxicity. To prepare a spatiotemporal controllable CPT nano-formulation, we construct a ROS-responsive self-assembly nanoparticle by combining hydrophobic CPT and hydrophilic 5-floxuridine (FUDR). A ROS-sensitive thioketal (TK) linker is used to prepare CPT-TK-FUDR (CTF). Next, we introduced IR780-based phototherapy to elicit massive ROS regeneration due to the endogenous ROS is not sufficient. IR780 is modified with hyaluronic acid (HA) to prepare HA-modified IR780 (HAIR) for its biocompatibility and tumor targeting ability improvement. CTF and HAIR self-assemble to form an attractive nano-bomb (HAIR/CTF NPs). HA accurately guides the NPs to tumor sites via HA-receptor recognition on tumor cells. After internalization, overexpressed intracellular HAase in tumor cells disassembles the NPs to free the contents. Due to the presence of IR780 molecules, the scheduled irradiation of 808 nm laser induces massive reactive oxygen species (ROS) generation, which further result in the cleavage of TK linker for free drugs release. Additionally, ROS-mediated photodynamic therapy (PDT) and near-infrared laser-mediated photothermal therapy (PTT) synergistically worked to eradicate tumor cells. Then immunogenic cell death (ICD) was evoked by CPT and phototherapy to amplify antitumor immunity, thereby achieving primary and abscopal tumor inhibition. In conclusion, the HAIR/CTF nano-bomb realized spatiotemporal controllable drug release, exciting tumor eradication and attractive anti-metastasis efficacy via combination chemo/photo/immunotherapy, offering a valuable reference for the re-development of classic drug in future clinical practice.
研究领域:
肿瘤学
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药学
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纳米技术
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癌症治疗
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Theranostics
·
2019
·
IF 8.063
Amin Zhang,Shaojun Pan,Yuhui Zhang,Jie Chang,Jin Cheng,Zhicheng Huang,Tianliang Li,Chunlei Zhang,Jesus Martinez de la Fuentea,Qian Zhang,Daxiang Cui
Rationale: Recently, there is one-fifth of human deaths caused by cancer, leading to cancer treatment remains a hard nut to crack in the medical field. Therefore, as an emerging diagnostic technology, mesoporous nanomaterials-based drug delivery systems integrated diagnosis and therapy have aroused tremendous interest owing to visually targeting effect and superior therapy efficacy compared with traditional cancer treatment. Methods: In this work, we have successfully synthesized mesoporous carbon-gold hybrid nanozyme nanoprobes, whereby mesoporous carbon nanospheres were doped with small gold nanoparticles (OMCAPs) and further stabilized with a complex of reduced serum albumin and folic acid (rBSA-FA). After loading IR780 iodide, the OMCAPs@ rBSA-FA@IR780 nanoprobes were finally accomplished for real-time imaging, photothermal/photodynamic and nanozyme oxidative therapy. Results: Herein, acid oxidized MCAPs possessed large surface area and numerous -COOH groups, which could be used to surface chemically modify numerous targeting molecules and load abundant NIR dye IR780, as well as be acted as photothermal reagents to enhance photothermal therapy effect. In addition, the small Au NPs embedded in OMCAPs were utilized as nanozyme to catalyze H 2 O 2 located in tumor cells to generate ·OH for intracellular oxidative damage of tumor. Besides, as a commonly used near-infrared (NIR) fluorescence dye, the loaded IR780 iodide could not only apply for real-time imaging, but also effectively enhance photo-thermal therapy (PTT) upon the 808 nm laser irradiation. Moreover, FA molecules could enhance the targeted efficiency of the nanoprobes to the gastric tumor site. According to the systematical study in vitro and in vivo , our fabricated nanoprobes based on carbon-gold hybrid (OMCAPs@ rBSA-FA@IR780) revealed excellent tumor targeting efficacy, long tumor retention and favorably therapeutic effect for tumor. Conclusion: All the results demonstrated that here synthesized probes exhibited excellently diagnostic and therapeutic performance, indicating our technology may potentially offer an outstanding strategy for tumor-targeting theranostics.
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
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Lu Zhang,Hongwei Tian,Ying Guo,Shuo Yu,Jin Sun,Hong Wang,Yang Zhao,Xi Chen,Huan Shen,Jing Geng,Guangyao Kong,Fu Wang,Zongfang Li
Traditional treatments for hepatocellular carcinoma (HCC) still lack effectiveness. Recently, the combined mode of chemodynamic therapy (CDT) and photothermal therapy (PTT) has shown great potential against HCC. However, insufficient Fenton reaction rates and hyperthermia-induced heat shock responses greatly impair their efficiency, hindering their further clinical application. Here, we constructed a cascade-amplified PTT/CDT nanoplatform by coating an IR780-embedded red blood cell membrane on glucose oxidase (GOx)-loaded Fe3O4 nanoparticles for effective HCC treatment. On the one hand, the nanoplatform interfered with glucose metabolism through the action of GOx to reduce the synthesis of ATP, which reduced the expression of heat shock proteins, thereby sensitizing the IR780-mediated PTT. On the other hand, hydrogen peroxide generated during GOx catalysis and the thermal effect of PTT accelerated the Fe3O4-mediated Fenton reaction, realizing enhanced CDT. Consequently, the sensitized PTT and enhanced CDT for HCC management could be simultaneously achieved by interfering with glucose metabolism, providing an alternative strategy for the effective treatment of tumors.
研究领域:
肿瘤学
·
生物医学工程
·
纳米技术
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Chenchen Wang,Xiaolei Song,Peng Li,Shihao Sun,Juan Su,Songqin Liu,Wei Wei
The excessive depositions of β-amyloid (Aβ) and abnormal level of reactive oxygen species (ROS) are considered as the important pathogenic factors of Alzheimer’s disease (AD). Strategies targeting only one of them have no obvious effects in clinic. In this study, a multifunctional nanocarrier CICe@M-K that crosses the blood–brain barrier (BBB) efficiently was developed for inhibiting Aβ aggregation and scavenging ROS synchronously. Antioxidant curcumin (Cur) and photosensitizer IR780 were loaded in mesoporous silica nanomaterials (MSNs). Their surfaces were grafted with cerium oxide nanoparticles (CeO2 NPs) and a short peptide K (CKLVFFAED). Living imaging showed that CICe@M-K was mainly distributed in the brain, liver, and kidneys, indicating CICe@M-K crossed BBB efficiently and accumulated in brain. After the irradiation of 808 nm laser, Cur was continuously released. Both of Cur and the peptide K can recognize and bind to Aβ through multiple interaction including π–π stacking interaction, hydrophobic interaction, and hydrogen bond, inhibiting Aβ aggregation. On the other hand, Cur and CeO2 NPs cooperate to relieve the oxidative stress in the brains by scavenging ROS. In vivo assays showed that the CICe@M-K could diminish Aβ depositions, alleviate oxidative stress, and improve cognitive ability of the APP/PS1 AD mouse model, which demonstrated that CICe@M-K is a potential agent for AD treatment.
研究领域:
神经科学
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药学
·
纳米技术
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2024
·
IF 5.8
Chengfang Wang,Size Wu
The treatment of unresectable locally advanced triple-negative breast cancer (TNBC) and TNBC with metastasis is challenging. Many anticancer drugs, such as doxorubicin, still hinder positive therapeutic outcomes due to severe side effects. Photodynamic therapy (PDT) has an anticancer effect, and combining PDT with chemotherapy may improve breast cancer therapy. The use of cargo-loaded biomimetic liposomes for cancer therapy may enhance efficacy and reduce side effects. In this study, liposomes were formulated to accommodate doxorubicin (Dox) and IR780. Breast cancer cells (4T1 cells) and macrophage cell membranes were isolated and camouflaged onto the liposomes, creating a new biomimetic platform called Dox-IR780@Lip@Ms. The Dox-IR780@Lip@Ms platform was characterized and tested in vitro and in vivo. The results showed that the Dox-IR780@Lip@Ms had an ovoid shape with a double lamina structure, monodispersity, and uniform distribution. The size was 132.37±1.22 nm, PDI was 0.044±0.067, and the zeta potential was -9.67±1.08 mV. The encapsulation efficiency of Dox and IR780 in Dox-IR780@Lip@Ms was 89.36%±3.07% and 92.34%±0.66%, respectively. The release rate of Dox from Dox-IR780@Lip@Ms was good after laser irradiation. At pH 7.4, the release rate of Dox was 23.85%±0.62% at 3h without laser irradiation and 36.62%±1.32% at 3.5h with laser irradiation. At pH 6.5, the release rate of Dox was 32.54%±0.32% at 3h without laser irradiation and 62.79%±2.15% at 3.5h with laser irradiation. The cytotoxicity of IR780@Lip@Ms was lower than that of Dox-IR780@Lip@Ms. The cell uptake and generation of reactive oxygen species of Dox-IR780@Lip@Ms were significant. Dox-IR780@Lip@Ms exhibited immune escaping ability in vitro, homotypic targeting ability to cancer cells, high capability to kill cancer cells after laser irradiation, minimal cardiotoxicity, increased accumulation of Dox and IR780 in the tumor, and increased anticancer effect in a tumor-bearing animal model. In conclusion, hybrid cell membranes of breast cancer and macrophages camouflaging liposomes loaded with Dox and IR780 can significantly improve breast cancer therapy after laser irradiation.
研究领域:
肿瘤学
·
药学
·
纳米技术
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2019
·
IF 10.273
Lu Lu,Xiaojing Zhao,Tiwei Fu,Ke Li,Ye He,Zhong Luo,Liangliang Dai,Rui Zeng,Kaiyong Cai
Various obstacles impede the chemotherapy efficiency of glioma in clinic, such as blood brain barrier (BBB) and blood brain tumor barrier (BBTB). Ligand-mediated polymeric micelles have shown great potential for improving the efficiency of glioma treatment. Herein, we developed a disulfide bond-conjugated prodrug polymer consisted of camptothecin (CPT) and polyethylene glycol (PEG) with further modification of iRGD peptide. The polymer of CPT-S-S-PEG-COOH could self-assemble into nanosized polymeric micelles with diameter around 100 nm, and loaded with photosensitizer IR780 for combination therapy. The micelles displayed good stability with controlled drug release under physiological environment. Importantly, the iRGD modified polymeric micelles demonstrated favorable ability to cross the BBB and target glioma cells via αv β integrin and neuropilin-1-mediated ligand transportation in vitro and in vivo . The whole synthesis process is simple and the drug loading content of CPT in the [email protected] micelles was higher than 10%. Moreover, [email protected] micelles combined chemotherapy with photodynamic therapy (PDT) displayed more excellent tumor-killing capability than the other groups. Thus, both in vitro and in vivo studies suggested that the targeting prodrug system could not only effectively cross various barriers to reach at glioma site, but also significantly enhance the antitumor effect with laser irradiation . Our findings consequently suggested that [email protected] micelles with laser irradiation are a promising drug delivery system for glioma therapy.
研究领域:
药学
·
纳米技术
·
神经肿瘤学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2024
·
IF 9.4
Cong Tang,Kairui Liu,Xiaoning Gao,Hanmeixuan Kang,Weijie Xie,Jin Chang,Linling Yin,Jun Kang
Cuproptosis is an emerging form of programmed cell death and shows enormous prospect in cancer treatment. Excessive generation of reactive oxygen species (ROS), metal ion accumulation, and the tricarboxylic acid (TCA) cycle collapse are pivotal elements in the triggering of cell death via mitochondrial pathways. Herein, a cascade nanoreactor CaCuZC has been constructed by incorporating nanosonosensitizer IR780 carbon dots (IR780 CD) and calcium peroxide (CaO 2 ) into metal-organic frameworks (MOF) for synergistic cuproptosis–ferroptosis and Ca 2+ overload mediated immunotherapy. Within tumor cells, CaCuZC dissociates into CaO 2 , Cu 2+ and sonosensitizer IR780 CD. The decomposition of CaO 2 could generate H 2 O 2 to strengthen the Cu 2+ -based chemodynamic therapy and Ca 2+ overload induces amplified intracellular oxidative stress, thus leading to mitochondrial dysfunction. As a result, the combination of Cu 2+ and Ca 2+ overload together induce cascade mitochondrial damage. Moreover, the sonosensitizer IR780 CD generates ROS under ultrasound irradiation to amplify intracellular oxidative stress. In addition, the overloaded Cu 2+ released from CaCuZC leads to the aggregation of lipoylated protein dihydrolipoamide S-acetyltransferase, thus resulting in cuproptosis. Furthermore, ferroptosis could been concomitantly induced by CaCuZC with intracellular glutathione (GSH) consumption and lipid peroxidation (LPO) accumulation. The cuproptosis–ferroptosis and Ca 2+ overload-enhanced synergistic therapy also activates robust immunogenic cell death. CaCuZC enhances the infiltration and activation of tumor-specific cytotoxic T cells to transform a “cold” tumor into a “hot” tumor, activating the anti-tumor immune response. This study provides a cascade of mitochondrial damage strategy for triggering cuproptosis–ferroptosis and Ca 2+ overload-enhanced immunotherapy and achieving improved therapeutic effects. Statement of significance To improve the efficacy of tumor immunotherapy, a cascade nanoreactor CaCuZC was successfully constructed based on a self-assembly strategy for cuproptosis–ferroptosis and Ca 2+ overload mediated immunotherapy. Upon decomposition within the acidic and GSH-overexpressing tumor microenvironment, CaCuZC released CaO 2 and Cu 2+ and sonosensitizer IR780 CD. The CaO 2 further produced H 2 O 2 /O 2 and Ca 2+ in a weakly acidic environment to strengthen the Cu 2+ -based CDT and IR780 CD-mediated SDT, respectively. The overload copper ions not only led to cuproptosis, but also efficiently induced ferroptosis. The cuproptosis–ferroptosis and Ca 2+ overload-enhanced synergistic therapy also activates robust immunogenic cell death. This study presents a cascade of mitochondrial damage strategy for cuproptosis–ferroptosis and Ca 2+ overload-enhanced immunotherapy.
研究领域:
癌症研究
·
纳米技术
·
治疗学
·
免疫学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2019
·
IF 8.456
Jing Zhang,Di Zhang,Qian Li,Yue Jiang,Aixin Song,Zhonghao Li,Yuxia Luan
Potentiating systemic immunity against breast cancer is in the most urgent demand as breast cancer is less sensitive to immune checkpoint blockade. Although phototherapy and some chemotherapy can trigger immunogenic cell death (ICD) for T cell-mediated antitumor immune response, their immunotherapy efficacy is severely restricted by insufficient phototherapeutic capability and severe multidrug resistance (MDR). Inspired by both the hypersensitivity to phototherapy and the key role of MDR for mitochondria, a rationally engineered immunity amplifier via mitochondria-targeted photochemotherapeutic nanoparticles was, for the first time, achieved to fight against low-immunogenic breast cancer without additional immune agents. The newly synthesized task-specific mitochondria-targeted IR780 derivative (T780) was integrated with chemotherapeutic doxorubicin (DOX) to form multifunctional nanoparticles via an assembling strategy along with bovine serum albumin (BSA) as a biomimetic corona (BSA@T780/DOX NPs). The in situ enhancement in both phototherapy and MDR reversal by targeting mitochondria with BSA@T780/DOX NPs boosted highly efficient ICD toward excellent antitumor immune response. The newly developed strategy not only eradicated the primary tumor but also eliminated the bilateral tumors efficiently, as well as preventing metastasis and postsurgical recurrence, demonstrating great interest for fighting against low-immunogenic breast cancer.
研究领域:
癌症研究
·
纳米技术
·
免疫疗法
·
药物科学
·
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）