BIOMATERIALS
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2016
·
IF 8.387
Yongjian Jiang,Shaojun Liu,Yu Zhang,Hengchao Li,Hang He,Juntao Dai,Tao Jiang,Weihang Ji,Daoying Geng,Ahmed A. Elzatahry,Abdulaziz Alghamdi,Deliang Fu,Yonghui Deng,Dongyuan Zhao
Immobilization of a ligand that selectively interacts with cancer cells to nanomaterials can enhance their diagnostic and therapeutic efficiency. In this study, we firstly demonstrate the high expression of receptor for cyclic nine-amino acid peptide LyP-1 (Cys-Gly-Asn-Lys-Arg-Thr-Arg-Gly-Cys) in both mouse and human pancreatic cancer. Based on these findings, sub-50 nm multifunctional superparamagnetic mesoporous nanospheres with surface modified with LyP-1 are rationally designed. Theses nanospheres have a core of silica-protected magnetite nanoparticle and a shell of FITC-labeled mesoporous silica , and they are able to specifically recognize and conjugate with the pancreatic cancer cell in vitro, as verified by the combined techniques of fluorescent imaging and T2 weight magnetic resonance imaging. After systematic administration, these LyP-1 immobilized nanospheres are found to actively target to mouse orthotopic xenograft of pancreatic cancer, which opens up the door for applications in early probing and diagnosis of pancreatic cancer by the multimodal imaging.
研究领域:
纳米技术
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癌症研究
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医学成像
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2016
·
IF 8.387
WenTing Li,JinRong Peng,LiWei Tan,Jing Wu,Kun Shi,Ying Qu,XiaWei Wei,ZhiYong Qian
Patients suffering from cancer have benefited from combination therapy. Nanocarriers are the ideal candidates for combination therapy. In this study, we constructed docetaxel (DTX) loaded micellar nanomedicines co-loaded with near infrared (NIR) dye-IR820 for photothermal therapy (PTT)/photodynamic therapy (PDT)/chemotherapy of breast cancer. Lyp-1, a tumor homing peptide, was introduced into the nanosystems to construct the active targeting nanomedicine. In order to deliver IR820 to the tumor site and overcome its short lifetime in vivo , a PEI derivative—PCL-g-PEI was introduced. IR820 with negative charge was formed stable static interaction with the amine groups, meanwhile, the absorption of IR820 in the NIR region was weakened. It indicated that the nanosystem constructed in this study may provide an alternative candidate for mild PTT. By the evaluation of the photothermal conversion in vivo , we can confirm that IR820 has been successfully delivered and effectively accumulated in the tumor site. Furthermore, the tumor cells targeting and anticancer performances of this nanosystem have been studied in vitro and in vivo . The results demonstrated Lyp-1 modification has enhanced the tumor targeting delivery of DTX and IR820. By combining PTT and PDT, DTX nanomedicine efficiently inhibited the growth and metastasis of breast cancer in mice. This nanosystem is a promising candidate for combination therapy of breast cancer.
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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治疗学
✓ 已验证
DOI
PubMed
高影响因子
MOLECULAR IMAGING AND BIOLOGY
·
2026
·
IF 2.5
Liao Sisi,Qi Qinli,Jin Lifang,Gong Jiali,Zhao Lingzhou,Zhao Jinhua,Zhu Meilin,Song Ningning
Purpose Sunitinib is an anti-angiogenic drug that can induce drug resistance characterized by hypoxia. We aimed to synthesize two novel radiolabeled LyP-1 peptides, 99m Tc-HYNIC-LyP-1 and 131 I-LyP-1, to detect sunitinib-induced changes in the tumor microenvironment and improve the therapeutic effects in triple-negative breast cancer (TNBC) mice models. Methods We synthesized 99m Tc-HYNIC-LyP-1 using hydrazinonicotinamide (HYNIC) as the chelating agent and labeled the LyP-1 peptide with 131 I using the chloramine-T method to synthesize 131 I-LyP-1. Radiochemical purity and stability of the peptides were assessed in vitro using thin-layer chromatography. Tumor accumulation and biodistribution of 99m Tc-HYNIC-LyP-1 were measured in 4T1 xenografts with or without sunitinib treatment. Immunohistochemical analysis was performed to detect sunitinib-induced changes. The therapeutic potential of 131 I-LyP-1 alone and in combination with sunitinib was evaluated in a TNBC mouse model. Results 99m Tc-HYNIC-LyP-1 and 131 I-LyP-1 could be readily prepared with satisfactory labeling efficiency (95.4% ± 0.6% and 72.5% ± 4.5%, respectively) and stability (both more than 90%) in vitro. Micro-single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging of mice transplanted with 4T1 tumors using 99m Tc-HYNIC-LyP-1 demonstrated that the uptake of this probe was high in 4T1 xenografts treated with sunitinib at 90 min, whereas it was mild in the control group. Semiquantitative analysis of the ratio of radioactivity intensity at tumor site to that of adjacent muscles (T/M value) showed that the average T/M value of the sunitinib treatment group at 90 min was 3.27, while it was 0.91 in the control group ( p = 0.0022). 131 I-LyP-1 could significantly inhibited tumor growth with good organ compatibility and had a synergistic therapeutic effect when combined with sunitinib, with an approximately threefold reduction in the tumor volume in comparison with the control group Conclusion Micro-SPECT/CT imaging using 99m Tc-HYNIC-LyP-1 can be used to monitor sunitinib-induced changes in the TNBC tumor microenvironment. The combination of 131 I-LyP-1 and sunitinib may serve as a novel treatment for TNBC.
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2020
·
IF 7.727
Xueqing Zhang,Yamei Huang,Heliang Song,Brandon S.B. Canup,Shuangquan Gou,Zhigang She,Fangyin Dai,Bowen Ke,Bo Xiao
Lung metastasis of breast cancer is a leading cause of cancer-related death in women. Herein, we attempted to simultaneously inhibit the growth and lung metastasis of breast cancer by delivering quercetin (QU) using LyP-1-functionalized regenerated silk fibroin-based nanoparticles (NPs). The generated LyP-1-QU-NPs had a desirable diameter (203.2 nm) and a negatively charged surface (−12.7 mV). Interestingly, these NPs exhibited intrinsic responsibilities when triggered by various stimulating factors in the tumor microenvironment (acidic pH, reactive oxygen species , and glutathione). In vitro experiments revealed that the introduction of LyP-1 to the NP surface could significantly increase their cellular uptake efficiencies by 4 T1 cells, and facilitate their accumulation in mitochondria. Moreover, LyP-1-QU-NPs showed the strongest mitochondrial damage effect among all the treatment groups. We also found that LyP-1-QU-NPs not only exhibited excellent pro-apoptotic activities but also presented strong inhibitory effects on cell mobility (migration and invasion) through anti-glycolysis and pro-autophagy. Mice experiments confirmed that LyP-1-QU-NPs could efficiently inhibit the in situ growth of breast tumors and further restrict their lung metastasis. Collectively, our results demonstrate that LyP-1-QU-NPs, which integrates the functions of tumor cell targeting, mitochondria targeting, bioresponsive drug release, pro-apoptosis, and anti-mobility, can be developed as a promising nanotherapeutic for the effective treatment of breast cancer and its lung metastasis.
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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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
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2017
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IF 13.942
Xujiang Yu,Ang Li,Chengzhi Zhao,Kai Yang,Xiaoyuan Chen,Wanwan Li
Multifunctional nanomaterials with integrated diagnostic and therapeutic functions, combination therapy to enhance treatment efficacy, as well as low toxicity have drawn tremendous attentions. Herein, we report a multifunctional theranostic agent based on peptide (LyP-1)-labeled ultrasmall semimetal nanoparticles of bismuth (Bi-LyP-1 NPs). Ultrasmall Bi NPs (3.6 nm) were facilely synthesized using oleylamine as the reducing agent and exhibited a higher tumor accumulation after being conjugated with the tumor-homing peptide LyP-1. The abilities to absorb both ionizing radiation and the second near-infrared (NIR-II) window laser radiation ensured that Bi-LyP-1 NPs are capable of dual-modal computed tomography/photoacoustic imaging and efficient synergistic NIR-II photothermal/radiotherapy of tumors. Moreover, Bi-LyP-1 NPs could be rapidly cleared from mice through both renal and fecal clearance and almost completely cleared after 30 days. Such multifunctional nanoparticles as efficient cancer theranostic agents, coupled with fast clearance and low toxicity, shed light on the future use of semimetal nanoparticles for biomedicine.
研究领域:
生物医学工程
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癌症治疗
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纳米技术
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诊断成像
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放射治疗
✓ 已验证
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2019
·Vol. 29
·期 19
·1900004
·
IF 15.621
Jinrong Peng,Qian Yang,Yao Xiao,Kun Shi,Qingya Liu,Ying Hao,Fan Yang,Ruxia Han,Zhiyong Qian
Nanomedicine constructed by therapeutics has unique and irreplaceable advantages in biomedical applications, especially in drug delivery for cancer therapy. The strategy, however, used to construct the therapeutics-based nanomedicines with tumor microenvironmental factor responsiveness is still sophisticated. In this study, an easy-operating procedure is used to construct a therapeutics-based nanosystem with active tumor-targeting, enhanced penetration, and stimuli-responsive drug release behavior as well as programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) blockading mediated immunomodulation to enhance tumor immunotherapy. The matrix metalloproteinase-2 responsive peptide with the existence of Lyp-1 sequence contributes to the success of active tumor-targeting and the enhancement of the penetration of the nanoparticles in tumor tissue. The obtained nanosystem strikingly inhibits the primary tumor growth in the first 24 h (more than 97.5% of tumor cells are inhibited), and total inhibition can be achieved with the combination of photothermal therapy. IR820, which is served as the carrier for the therapeutics, is used as a photosensitizer for photothermal therapy. The progress and aggression of distal tumor has further been alleviated by a d -peptide which is an antagonist for PD-1/PD-L1 blockage. Therefore, a therapeutics-constructed multifunctional nanosystem is provided to realize a combinational therapeutic strategy to enhance the therapeutic outcome.
研究领域:
癌症治疗
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纳米医学
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药学
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免疫治疗
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生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
Acta Biomaterialia
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2018
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IF 6.383
Fengchun Tian,Fatima Zohra Dahmani,Jianan Qiao,Jiang Ni,Hui Xiong,Tengfei Liu,Jianping Zhou,Jing Yao
Several obstacles are currently impeding the successful treatment of breast cancer, namely impaired drug accumulation into the tumor site, toxicity to normal cells and narrow therapeutic index of chemotherapy, multidrug resistance (MDR) and the metastatic spread of cancer cells through the blood and lymphatic vessels. In this regard, we designed a novel multifunctional nano-sized drug delivery system based on LyP-1 peptide-modified low-molecular-weight heparin-quercetin conjugate (PLQ). This nanosystem was developed for targeted co-delivery of multiple anticancer drugs to p32-overexpressing tumor cells and peritumoral lymphatic vessels, using LyP-1 peptide as active targeting ligand, with the aim to achieve a targeted combinatorial chemo/angiostatic therapy and MDR reversal. The cellular uptake of PLQ nanoparticles by p32-overexpressing breast cancer cells was significantly higher than nonfunctionalized nanoparticles. Besides, the anti-angiogenic activity of PLQ nanoparticles was proven by the effective inhibition of the bFGF-induced neovascularization in subcutaneous Matrigel plugs. More importantly, PLQ/GA nanoparticles with better targeting ability toward p32-positive tumors, displayed a high antitumor outcome by inhibition of tumor cells proliferation and angiogenesis . Immunohistochemistry and western blot assay showed that PLQ/GA nanoparticles significantly disrupted the lymphatic formation of tumor, and inhibited the P-glycoprotein (P-gp) expression in MCF-7 tumor cells, respectively. In conclusion, PLQ/GA nanoparticles provide a synergistic strategy for effective targeted co-delivery of chemotherapeutic and antiangiogenic agents and reversing MDR and metastasis in breast cancer. Statement of Significance Herein, we successfully developed a novel amphiphilic nanomaterial , LyP-1-LMWH-Qu (PLQ) conjugate, consisting of a tumor-targeting moiety LyP-1, a hydrophobic quercetin (a multidrug resistance [MDR]–reversing drug) inner core, and a hydrophilic low-molecular-weight heparin (an antiangiogenic agent) outer shell for encapsulating and delivering a hydrophobic chemotherapeutic agent (gambogic acid). This versatile nanoplatform with multiple targeted features, i.e., dual chemo/angiostatic effects, destruction ability of the peritumoral lymphatic vessels, and reversal of MDR, resulted in a significantly stronger antitumor efficacy and lower toxic side effect than those of nontargeted nanoparticles and the free drug solution. Therefore, this versatile nanosystem might provide a novel insight for the treatment and palliation of breast cancer by targeted co-delivery of chemo/antiangiogenic agents and reversing MDR and metastasis.
研究领域:
肿瘤学
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药理学
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纳米技术
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癌症治疗
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）