Asian Journal of Pharmaceutical Sciences
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2023
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IF 10.2
Shan Gao,Meng Liu,Dongzhu Liu,Xinru Kong,Yuelin Fang,Yingying Li,Hang Wu,Jianbo Ji,Xiaoye Yang,Guangxi Zhai
Growing evidence suggests that the presence of cancer stem cells (CSCs) is a major challenge in current tumor treatments, especially the transition from non-CSCs to differentiation of CSCs for evading conventional therapies and driving metastasis. Here we propose a therapeutic strategy of synergistic differentiation therapy and phototherapy to induce differentiation of CSCs into mature tumor cells by differentiation inducers and synergistic elimination of them and normal cancer cells through phototherapy. In this work, we synthesized a biomimetic nanoplatform loaded with IR-780 and all-trans retinoic acid (ATRA) via biomineralization. This method can integrate aluminum ions into small-sized protein carriers to form nanoclusters, which undergo responsive degradation under acidic conditions and facilitate deep tumor penetration. With the help of CSC differentiation induced by ATRA, IR-780 inhibited the self-renewal of CSCs and cancer progression by generating hyperthermia and reactive oxygen species in a synergistic manner. Furthermore, ATRA can boost immunogenic cell death induced by phototherapy, thereby strongly causing a systemic anti-tumor immune response and efficiently eliminating CSCs and tumor cells. Taken together, this dual strategy represents a new paradigm of targeted eradication of CSCs and tumors by inducing CSC differentiation, improving photothermal therapy/photodynamic therapy and enhancing antitumor immunity.
研究领域:
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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免疫疗法
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产品关联
DOI
PubMed
高影响因子
Theranostics
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2020
·
IF 8.579
Wanbing Qin,Guilan Quan,Ying Sun,Minglong Chen,Peipei Yang,Disang Feng,Ting Wen,Xinyu Hu,Xin Pan,Chuanbin Wu
High aggressiveness and recurrence of melanoma tumors require multiple systemic drug administrations, causing discomfort and severe side effects to the patients. Topical treatment strategies that provide repetitively controllable and precise drug administrations will greatly improve treatment effects. Methods: In this study, a spatiotemporally controlled pulsatile release system, which combined dissolving microneedles (DMNs) and thermal-sensitive solid lipid nanoparticles (SLNs), was constructed to realize multiple doses of dual-modal chemo-photothermal therapy in a single administration. Paclitaxel (PTX) and photothermal agent IR-780 were encapsulated into SLNs and were concentrated in the tips of DMNs (PTX/IR-780 SLNs @DMNs). Equipped with several needles, the DMN patch could be directly inserted into the tumor site and provide a stable “Zone accumulation” to constrain the PTX/IR-780 SLNs at the tumor site with uniform distribution. Results: In vitro experiments showed that after irradiation with near-infrared light, the PTX/IR-780 SLNs gradually underwent phase transition, thereby accelerating the release of PTX. When irradiation was switched off, the PTX/IR-780 SLNs cooled to re-solidify with limited drug release. Compared with intravenous and intratumoral injections, very few SLNs from PTX/IR-780 SLNs @DMNs were distributed into other organs, resulting in enhanced bioavailability at the tumor site and good safety. In vivo analysis revealed that PTX/IR-780 SLNs @DMNs exhibited significant anti-tumor efficacy. In particular, the primary tumor was completely eradicated with a curable rate of 100% in 30 days and the highest survival rate of 66.67% after 100 days of treatment. Conclusion: Herein, we developed a DMN system with a unique spatiotemporally controlled pulsatile release feature that provides a user-friendly and low-toxicity treatment route for patients who need long-term and repeat treatments.
研究领域:
药学
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癌症治疗
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纳米技术
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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
Materials Science & Engineering C-Materials for Biological Applications
·
2021
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IF 7.328
Linna Chang,Shuocheng Huang,Xingjun Zhao,Yanan Hu,Xiuli Ren,Xifan Mei,Zhenhua Chen
Photothermal responsive nanoplatforms are attracting for photothermal therapy (PTT) of cancer. Herein, we propose a strategy to prepare IR-780 modified hydroxyapatite (HAP) nanorods as photothermic agents ( [email protected] ). The results demonstrated that the obtained [email protected] was photothermal responsive under near-infrared laser irradiation the photothermal conversion efficiency was 69.3%, and it remained photostability after 4 cycles of irradiation. This advantage overcomes the optical instability of IR780. MTT and cellular uptake research proved that [email protected] was biocompatible in appropriate concentration range (0–20 μg/mL) without laser irradiation. Concentration-dependent internalization and reactive oxygen species (ROS) related apoptosis of [email protected] for MCF-7 cells were observed. Animal experiments showed that the gathered [email protected] at the tumor site reached a photothermal responsive temperature up to 57.9 °C, which could almost ablate the tumor with volumes as large as 1500 mm 3 . In general, our photothermal material has good photothermal conversion characteristics, and may have the least safety problems while showing excellent therapeutic effects. Therefore, [email protected] has a brilliant prospect in the field of tumor photothermal therapy.
研究领域:
纳米技术
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癌症治疗
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材料科学
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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
PARTICLE & PARTICLE SYSTEMS CHARACTERIZATION
·
2020
·Vol. 37
·期 3
·1900427
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IF 3.099
Jia Zhou,Tianliang Li,Yiran Zhang,Xiaoyu Xu,Chunlei Zhang,Yuehua Li,Daxiang Cui,Yingsheng Cheng
Magnetic resonance imaging (MRI) contrast agents are broadly employed for better clinical trials in MR imaging. Magnevist solution (Gd-DTPA), a clinical MRI contrast agent, possesses inherent shortcomings like poor r 1 relaxation, short half-time, nephrotoxicity, etc. To overcome these problems, Gd-DTPA-grafted protein assemblies (Gd-P-ABs) loading with anticancer drug cisplatin and photosentizer IR-780 are constructed via chelation of Gd 3+ . Gd-P-ABs exhibit dual MR/fluorescence (FL) imaging–guided chemo/photothermal therapy. Interestingly, Gd-P-ABs behave as aggregation-enhanced magnetic resonance imaging with an extremely high r 1 value of 26.391 s −1 m m −1 , which is about 5.5-fold larger than Gd-DTPA (≈4.8 s −1 m m −1 ). Consequently, better MRI performance is presented with the same concentration of Gd ions. When exposed to acidic tumor microenvironment and light irradiation, Gd-P-ABs show significant drug release capacity. Good cell killing ability in vitro is also determined due to effective folate-targeting ability and high photo–heat conversion. In vivo MR/FL imaging results reveal that Gd-P-ABs possess high-sensitivity tumor-targeting imaging and long tumor retention, which are attributed to the folate-targeting ability and small size effect. Combined chemo/photothermal therapy in vivo demonstrates that the tumor can be eventually ablated. Altogether, the Gd-P-ABs possess great potential for clinical imaging-guided tumor therapy.
研究领域:
放射学
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分子影像
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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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产品关联
DOI
高影响因子
ACS Sensors
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2022
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IF 9.618
Yue Xu,Haiyan Chen,Shufen Xu,Ji Liu,Yang Chen,Lijuan Gui,Hua Li,Ruixi Li,Zhenwei Yuan,Bowen Li
Several photosensitizers have recently been proposed as novel approaches against β-lactamase-producing drug-resistant bacteria. However, these reported photosensitizers are rarely used for accurate recognition of drug-resistant bacteria. To tackle this challenge, the structurally modified photosensitizer CySG-2 based on a lipophilic cationic heptamethine indocyanine near-infrared (NIR) dye (IR-780) and an important synthesis intermediate of cephalosporin antibiotic (GCLE) not only achieved the accurate recognition of TEM-1 methicillin-resistant Staphylococcus aureus (MRSA) successfully but also achieved antimicrobial photodynamic therapy (aPDT) in animal models infected by drug-resistant bacteria. Accurate enzyme recognition and efficient photodynamic therapy capabilities allow CySG-2 to achieve one stone with two birds. In addition, CySG-2 could also promote the eradication of internalized MRSA by facilitating the autophagy process, which is synergistic with its capacity of inducing reactive oxygen species generation under NIR laser irradiation for aPDT. Collectively, it is an effective multifunctional photosensitizer with the potential ability to guide the optimal use of different antibiotics and apply them in clinical treatment.
研究领域:
药学
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微生物学
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生物医学工程
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传染病学
✓ 已验证
DOI
PubMed
高影响因子
POLYMER
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2015
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IF 3.562
Haijie Han,Shimiao Zhang,Yin Wang,Tingting Chen,Qiao Jin,Yangjun Chen,Zuhong Li,Jian Ji
Miniemulsion reversible addition-fragmentation chain transfer (RAFT) polymerization was used to synthesize biomimetic poly (2-methacryloyloxyethyl phosphorylcholine)- b -Poly ( n -butyl methacrylate) (PMPC- b -PBMA) nanoparticles which were used as nanocarriers to encapsulate theranostic IR-780 molecules. IR-780 endowed the PMPC- b -PBMA nanoparticles with dual functions including tumor near-infrared (NIR) imaging and photothermal therapy (PTT). The IR-780 encapsulated PMPC- b -PBMA (PMPC- b -PBMA/IR-780) nanoparticles showed good monodispersity and significant stability. The photothermal effects and photothermal cytotoxicity of the PMPC- b -PBMA/IR-780 nanoparticles were studied in vitro . High accumulation of the PMPC- b -PBMA/IR-780 nanoparticles in tumor tissue was verified by whole-animal NIR imaging. The resulted IR-780 encapsulated biomimetic nanoparticles can be an alternative safe theranostic agent for imaging-guided cancer treatment.
研究领域:
生物材料学
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肿瘤学
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纳米医学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Hongzi Wu,Bowen Li,Jichun Shao,Qingquan Kong
The clinical use of chemotherapy for refractory osteosarcoma (OS) is limited due to its multiorgan toxicity. To overcome this challenge, new dosage forms and combination treatments, such as phototherapy, are being explored to improve targeted delivery and cytocompatibility of chemotherapeutic agents. In addition, inducing ferroptosis in iron-rich tumors could be a promising strategy to enhance OS therapy. In this study, a novel formulation was developed using natural biological H-ferritin (HFn) encapsulating the photosensitizer IR-780 and the chemotherapy drug gemcitabine (Gem) for OS-specific targeted therapy (HFn@Gem/IR-780 NPs). HFn@Gem/IR-780 NPs were designed to specifically bind and internalize into OS cells by interacting with transferrin receptor 1 (TfR1) which is overexpressed on the surface of OS cell membranes. The Gem and IR-780 were then released responsively under mildly acidic conditions in tumors. HFn@Gem/IR-780 NPs achieved cascaded antitumor therapeutic efficacy through the combination of chemotherapy and phototherapy under near-infrared irradiation in vitro and in vivo . Importantly, HFn@Gem/IR-780 NPs demonstrated excellent safety profile with significantly decreased drug exposure to normal organs, indicating its potential for reducing systemic toxicity. Thus, utilizing HFn as a vehicle to encapsulate highly effective antitumor drugs provides a promising approach for the treatment of OS metastasis and relapse.
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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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Polymer Materials
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2023
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IF 5
Jinjin Li,Ruyue Liu,Bingyan Zhang,Feifei Bai,Ling Zhao,Zhenhao Xi
In this work, a multimodal (chemotherapeutic/photodynamic/photothermal) theranostic nanodrug delivery platform was developed based on the synergetic action of self-framed polyphosphazene prodrug and heptamethine cyanine dye IR-780. First, an electronegative glutathione (GSH)-responsive polyphosphazene prodrug abbreviated as HGEH was prepared via multicomponent condensation reaction of genistein (GEN), bis-(4-hydroxyphenyl)-disulfide, and hexachlorocyclotriphosphazene. The particle size of drug (GEN)-containing HGEH nanoparticles is adjustable. Subsequently, cationic near-infrared photosensitizer IR-780 was adsorbed onto the electron-rich HGEH to obtain the multimodal theranostic nanodrug delivery platform HGEH-IR780. The platform was demonstrated to retain high stability in avoiding drug leakage and enable controlled drug release in response to the tumor microenvironment, in which a higher GSH concentration exists. The in vitro experiments show that HGEH-IR780 undergoes photothermal and photodynamic processes to concurrently generate heat and reactive oxygen species for efficiently killing mouse breast cancer cells (4T1) upon exposure to a single-bandwidth near-infrared laser (808 nm). Specifically, HGEH-IR780 inhibits 4T1 cells by up to 80% at a concentration of 100 μg/mL. The as-developed HGEH-IR780 exhibits promising results in GSH-responsive anticancer activity and photodynamic/photothermal therapy, which provides a reference for the construction of the polyphenol flavonoid multimodal therapeutic nanoplatform.
研究领域:
材料科学
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药学
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生物医学工程
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癌症研究
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纳米技术
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2023
·Vol. 21
·期 1
·1-23
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IF 10.2
Pan Yi,Liu Longcai,He Yichen,Ye Luyi,Zhao Xin,Hu Zhiming,Mou Xiaozhou,Cai Yu
Background Triple-negative breast cancer (TNBC) possesses special biological behavior and clinicopathological characteristics, which is highly invasive and propensity to metastasize to lymph nodes, leading to a worse prognosis than other types of breast cancer. Thus, the development of an effective therapeutic method is significant to improve the survival rate of TNBC patients. Results In this work, a liposome-based theranostic nanosystem (ILA@Lip) was successfully prepared by simultaneously encapsulating IR 780 as the photosensitizer and lenvatinib as an anti-angiogenic agent, together with banoxantrone (AQ4N) molecule as the hypoxia-activated prodrug. The ILA@Lip can be applied for the near-infrared (NIR) fluorescence diagnostic imaging of TNBC and its lymph node metastasis for multimodal therapy. Lenvatinib in ILA@Lip can inhibit angiogenesis by cutting oxygen supply, thereby leading to enhanced hypoxia levels. Meanwhile, large amounts of reactive oxygen species (ROS) were produced while IR 780 was irradiated by an 808 nm laser, which also rapidly exhausted oxygen in tumor cells to worsen tumor hypoxia. Through creating an extremely hypoxic in TNBC, the conversion of non-toxic AQ4N to toxic AQ4 was much more efficiency for hypoxia-activated chemotherapy. Cytotoxicity assay of ILA@Lip indicated excellent biocompatibility with normal cells and tissues, but showed high toxicity in hypoxic breast cancer cells. Also, the in vivo tumors treated by the ILA@Lip with laser irradiation were admirably suppressed in both subcutaneous tumor model and orthotopic tumor models. Conclusion Utilizing ILA@Lip is a profound strategy to create an extremely hypoxic tumor microenvironment for higher therapeutic efficacy of hypoxia-activated chemotherapy, which realized collective suppression of tumor growth and has promising potential for clinical translation.
研究领域:
肿瘤学
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生物医学工程
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药学
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诊断成像
✓ 已验证
DOI
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2016
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IF 3.782
Hong Liu,Yan Tan,Lisi Xie,Lei Yang,Jing Zhao,Jingxuan Bai,Ping Huang,Wugen Zhan,Qian Wan,Chao Zou,Yali Han,Zhiyong Wang
Stem cells hold great promise for treating various diseases. However, one of the main drawbacks of stem cell therapy is the lack of non-invasive image-tracking technologies. Although magnetic resonance imaging (MRI) and near-infrared fluorescence (NIRF) imaging have been employed to analyse cellular and subcellular events via the assistance of contrast agents, the sensitivity and temporal resolution of MRI and the spatial resolution of NIRF are still shortcomings. In this study, superparamagnetic iron oxide nanocrystals and IR-780 dyes were co-encapsulated in stearic acid-modified polyethylenimine to form a dual-modality contrast agent with nano-size and positive charge. These resulting agents efficiently labelled stem cells and did not influence the cellular viability and differentiation. Moreover, the labelled cells showed the advantages of dual-modality imaging in vivo.
研究领域:
生物医学工程
·
干细胞研究
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医学成像
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纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2024
·
IF 6.6
Meng Wei,Xiaobo Wang,Yunhai Mo,Cunqing Kong,Mengqi Zhang,Guanhua Qiu,Zhihong Tang,Jie Chen,Feixiang Wu
Introduction Current therapeutic strategies, including immune checkpoint blockade (ICB), exhibit limited efficacy in treating hepatocellular carcinoma (HCC). Nanoparticles, particularly those that can accumulate specifically within tumors and be activated by sonodynamic therapy (SDT), can induce immunogenic cell death (ICD); however, ICD alone has not achieved satisfactory therapeutic effectiveness. This study investigates whether combining ICB with ICD induced by nanoparticle-mediated SDT could enhance anti-tumor immunity and inhibit HCC growth.Methods We developed an iron-based micelle nanodelivery system encapsulating the Near-Infrared Dye IR-780, which was surface-modified with a cyclic tripeptide composed of arginine-glycine-aspartic acid (cRGD). This led to the synthesis of targeted IR780@FOM-cRGD nanoparticles. These nanoparticles were specifically engineered to kill tumor cells under sonication, activate immunogenic cell death (ICD), and be used in conjunction with immune checkpoint blockade (ICB) for the treatment of hepatocellular carcinoma (HCC).Results The synthesized IR780@FOM-cRGD nanoparticles had an average diameter of 28.23±1.750 nm and a Zeta potential of −23.95±1.926. Confocal microscopy demonstrated that IR780@FOM-cRGD could target HCC cells while minimizing toxicity to healthy cells. Upon sonodynamic activation, these nanoparticles consumed significant amounts of oxygen and generated substantial reactive oxygen species (ROS), effectively killing tumor cells and inhibiting the proliferation, invasion, and migration of H22 cells. Hemolysis assays confirmed the in vivo safety of the nanoparticles, and in vivo fluorescence imaging revealed significant accumulation in tumor tissues. Mouse model experiments showed that combining ICB(which induced by Anti-PD-L1) with ICD (which induced by IR780@FOM-cRGD), could effectively activated anti-tumor immunity and suppressed tumor growth.Discussion This study highlights the potential of IR780@FOM-cRGD nanoparticles to facilitate tumor eradication and immune activation when used in conjunction with Anti-PD-L1 therapy. This combination represents a non-invasive, efficient, and targeted approach for the treatment of hepatocellular carcinoma (HCC). By integrating sonodynamic therapy with immunotherapy, this strategy promises to substantially improve the effectiveness of traditional treatments in combating HCC, offering new avenues for clinical application and therapeutic innovation.
研究领域:
肿瘤学
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纳米技术
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免疫治疗
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癌症生物学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）