Theranostics
·
2018
·
IF 8.537
Zaigang Zhou,Baoli Zhang,Haoran Wang,Ahu Yuan,Yiqiao Hu,Jinhui Wu
Tumors are usually hypoxic, which limits the efficacy of current tumor therapies, especially radiotherapy in which oxygen is essential to promote radiation-induced cell damage. Herein, by taking advantage of the ability of perfluorocarbon (PFC) to promote red blood cell penetration, we developed a simple but effective two-stage oxygen delivery strategy to modulate the hypoxic tumor microenvironment using PFC nanoparticles. Methods: We first examined the two-stage oxygen delivery ability of PFC nanoparticles on relieving tumor hypoxia through platelet inhibition. To evaluate the effect of PFC nanoparticles on radiation sensitization, CT26 tumor and SUM49PT tumor model were used. Results: In this study, PFC was encapsulated into albumin and intravenously injected into tumor-bearing mice without hyperoxic breathing. After accumulation in the tumor, PFC nanoparticles rapidly released the oxygen that was physically dissolved in PFC as the first-stage of oxygen delivery. Then, PFC subsequently promoted red blood cell infiltration, which further released O 2 as the second-stage of oxygen delivery. Conclusion: The hypoxic tumor microenvironment was rapidly relieved via two-stage oxygen delivery, effectively increasing radiotherapy efficacy. The safety of all substances used in this study has been clinically demonstrated, ensuring that this simple strategy could be rapidly and easily translated into clinical applications to solve the clinical problems associated with tumor hypoxia.
研究领域:
肿瘤学
·
纳米技术
·
放射生物学
·
治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2023
·
IF 10
Jingyi Yang,Jiahao Qu,Xuanming Teng,Weiping Zhu,Yufang Xu,Yangyang Yang,Xuhong Qian
Most solid tumors are clinically treated using surgical resection, and the presence of residual tumor tissues at the surgical margins often determines tumor survival and recurrence. Herein, a hydrogel (Apt-HEX/Cp-BHQ1 Gel, termed AHB Gel) is developed for fluorescence-guided surgical resection. AHB Gel is constructed by tethering a polyacrylamide hydrogel and ATP-responsive aptamers together. It exhibits strong fluorescence under high ATP concentrations corresponding to the TME (100–500 µ m ) but shows little fluorescence at low ATP concentrations (10–100 n m ) such as those in normal tissues. AHB Gel can rapidly (within 3 min) emit fluorescence after exposure to ATP, and the fluorescence signal only occurs at sites exposed to high ATP, resulting in a clear boundary between the ATP-high and ATP-low regions. In vivo, AHB Gel exhibits specific tumor-targeting capacity with no fluorescence response in normal tissue, providing clear tumor boundaries. In addition, AHB Gel has good storage stability, which is conducive to its future clinical application. In summary, AHB Gel is a novel tumor microenvironment-targeted DNA-hybrid hydrogel for ATP-based fluorescence imaging. It can enable the precise imaging of tumor tissues, showing promising application in fluorescence-guided surgeries in the future.
研究领域:
生物医学工程
·
癌症研究
·
材料科学
·
外科肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2024
·
IF 4.5
Xiaomeng Lu,Xinyu Zhan,Guozi Xia,Feifei Wang,Mingjia Lv,Renwei Liu,Yuxue Liu,Chen Zi,Guangyong Li,Rui Wang,Jun Li,Fengjiao Yuan,Dianlong Jia
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an attractive candidate for anticancer therapeutics due to its efficient pro-apoptotic activity against tumor cells and its well-tolerated safety profile. However, the in vivo antitumor efficacy of TRAIL is often limited by its poor tumor targeting capacity. Nowadays, the B7 homologue 3 (B7–H3) immune checkpoint has emerged as a promising target for tumor immunotherapy and drug delivery. Here, we report the achievement of tumor-targeted delivery of TRAIL by genetically fusing it with a B7H3-antagonistic affibody. The affibody–TRAIL fusion protein, named ACT, was easily expressed in Escherichia coli with a high yield and could form the active trimeric state. In vitro ACT showed significantly increased cellular binding to multiple B7H3-positive tumor cells and improved cytotoxicity by 2–3 times compared to the parent TRAIL. In vivo ACT demonstrated a 2.4-fold higher tumor uptake than TRAIL in mice bearing B7H3-positive A431 tumor grafts. More importantly, ACT exhibited significantly improved antitumor efficacy against tumors in vivo. In addition, ACT treatment did not cause body weight loss or histopathological changes in the major organs of mice, indicating its good safety profile. Overall, our findings demonstrate that targeting B7H3 to enhance TRAIL delivery is a viable approach to improve its therapeutic efficacy, and ACT may be a potential agent for targeted therapy of B7H3-positive tumors.
研究领域:
肿瘤学
·
免疫治疗
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Matter
·
2022
·
IF 19.967
Yunfei Yi,Mian Yu,Chan Feng,Huisong Hao,Weiwei Zeng,Chuchu Lin,Hongzhong Chen,Feng Lv,Dunwan Zhu,Xiaoyuan Ji,Lin Mei,Meiying Wu,Wei Tao
Summary It is highly desirable to turn “cold” tumors into “hot” ones to improve the efficacy of antitumor immunotherapy. Herein, we develop the peptide-based small interfering RNA (siRNA) micelleplexes (P A7R @siPD-L1) for normalizing vascular-immune crosstalk to establish a positive feedback loop in potentiating antitumor immunotherapy. These micelleplexes are equipped with tumor-microenvironment-responsive property for precise drug delivery and release. The prepared P A7R @siPD-L1-mediated photodynamic therapy could eliminate solid tumors and trigger immunogenic cell death to generate systematic immune responses. Meanwhile, the antiangiogenic peptide A7R normalizes the tumor vasculature by converting chaotic vascular systems into matured and organized ones, thus alleviating tumor hypoxia and promoting intratumoral infiltration by immune cells. Antitumor immunogenicity would be further strengthened with the aid of siPD-L1 by muting the resistance of tumor cells against immune effector cells. This study provides a unique therapeutic strategy in turning “cold” tumors into “hot” tumors enabled by siRNA nanomaterial .
研究领域:
肿瘤学
·
免疫疗法
·
纳米医学
·
癌症生物学
✓ 已验证
DOI
高影响因子
ACS Nano
·
2022
·
IF 18.027
Lingxiao Zhang,Yingbo Jia,Jinju Yang,Lun Zhang,Shengjie Hou,Xiaoyun Niu,Jie Zhu,Yaru Huang,Xiaoying Sun,Zhi Ping Xu,Ruitian Liu
Cancer immunotherapy efficacy is largely limited by the suppressive tumor immune microenvironment (TIME) where antitumor immune cells are inhibited and tumor antigens continue to mutate or be lost. To remodel the TIME, we here applied weakly alkaline layered double hydroxide nanoparticles (LDH NPs) to neutralize the excess acid and block autophagy of tumor cells for neoadjuvant cancer immunotherapy. Peritumoral injection of LDH NPs provided a long-term and efficient acid-neutralization in the TIME, blocked the lysosome-mediated autophagy pathway in tumor cells, and increased the levels of antitumor tumor-associated macrophages and T cells. These LDH NPs captured tumor antigens released in the tumor tissues and effectively inhibited the growth of both melanoma and colon tumors in vivo. These findings indicate that LDH NPs, as an immunomodulator and adjuvant, successfully “awaken” and promote the host innate and adaptive immune systems, showing promising potential for solid tumor immunotherapy.
研究领域:
癌症研究
·
纳米技术
·
免疫学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
Nature Biomedical Engineering
·
2020
·Vol. 4
·期 7
·732-742
·
IF 18.952
Li Suping,Zhang Yinlong,Ho Shih-Hsin,Li Bozhao,Wang Meifang,Deng Xiongwei,Yang Na,Liu Guangna,Lu Zefang,Xu Junchao,Shi Quanwei,Han Jing-Yan,Zhang Lirong,Wu Yan,Zhao Yuliang,Nie Guangjun
Drugs that induce thrombosis in the tumour vasculature have not resulted in long-term tumour eradication owing to tumour regrowth from tissue in the surviving rim of the tumour, where tumour cells can derive nutrients from adjacent non-tumoral blood vessels and tissues. Here, we report the performance of a combination of tumour-infarction therapy and chemotherapy, delivered via chitosan-based nanoparticles decorated with a tumour-homing peptide targeting fibrin–fibronectin complexes overexpressed on tumour-vessel walls and in tumour stroma, and encapsulating the coagulation-inducing protease thrombin and the chemotherapeutic doxorubicin. Systemic administration of the nanoparticles into mice and rabbits bearing subcutaneous or orthotopic tumours resulted in higher tumour growth suppression and decreased tumour recurrence than nanoparticles delivering only thrombin or doxorubicin, with histological and haematological analyses indicating an absence of detectable toxicity. The co-administration of a cytotoxic payload and a protease to elicit vascular infarction in tumours with biodegradable tumour-targeted nanoparticles represents a promising strategy for improving the therapeutic index of coagulation-based tumour therapy.
研究领域:
肿瘤学
·
药学
·
纳米技术
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
NPG Asia Materials
·
2018
·Vol. 10
·期 10
·1002-1015
·
IF 7.208
Huang Yanyu,Mei Chaoming,Tian Yiqiao,Nie Tianqi,Liu Zhuang,Chen Tianfeng
Rational design of smart nanosystems with high biological safety is a critical milestone for realizing precise imaging-guided cancer theranostics. Herein, a bioinspired nanosystem was designed by camouflaging SPIO@DOX-ICG nanoparticles with cancer cell membrane (CCM) to realize precise cancer treatment through simultaneous chemotherapy, hyperthermia-therapy, and radiotherapy. CCM surface decoration preserves the cancer adhesion molecules and surface antigens in the nanosystem, endowing the nanosystem with tumor-homing ability and high biocompatibility. Guided by dual-modal imaging, the nanosystem specifically accumulated in the tumor region and achieved synergistic anticancer effects after combined treatment, without causing toxic side effects in major organs. Interestingly, the combined treatment also antagonized tumor hypoxia and reprogrammed the polarization of tumor associated macrophages to the antitumor M1 phenotype. Taken together, this study offers a smart strategy for designing a bioinspired tumor-homing nanosystem for precise cancer therapy.
研究领域:
纳米技术
·
癌症治疗
·
生物医学工程
·
免疫学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF FLUORESCENCE
·
2021
·Vol. 31
·期 2
·339-348
·
IF 2.217
Lv Rongyao,Li Genrong,Lu Shuting,Wang Ting
Carbon dots are nano-sized photoluminescence materials which have good biocompatibility and low cytotoxicity, while the previously synthesized carbon dots lack tumor targeting capability and therapy function so that it cannot achieve the purpose of diagnosis and treatment. Herein, a new kind of multi-functional carbon dots (GFCDs) is promising to be applied in tumor cells imaging and clinical targeted therapy. Gallic acid (GA) was used as the carbon resource and antitumor active molecule, folic acid (FA) was used as the nitrogen resource and tumor targeting molecule, and citric acid monohydrate (CA) was used as the auxiliary carbon source. Multi-functional GACDs were synthesized by a simple one-step microwave-assisted procedure and analyzed with UV − vis spectrophotometer, fourier transform infrared spectrometer, transmission electron microscopy and X-ray photoelectron spectrometer. Results show that the diameter of GFCDs is about 3 nm. And GFCDs are pale-yellow under natural light which turn blue under 360 nm UV lamp. Besides ester bond is the connecting mode between functional molecules. In addition, the results of in vitro cell imaging experiments and in vivo antitumor experiments demonstrate the targeting imaging and antitumor abilities towards Hela cells. Graphical abstract
The synthesis route and properties of GFCDs.
研究领域:
生物医学工程
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2020
·
IF 8.758
Kun Tu,Huan Deng,Li Kong,Yi Wang,Ting Yang,Qian Hu,Mei Hu,Conglian Yang,Zhiping Zhang
Blocking immune checkpoints with monoclonal antibody has been verified to achieve potential clinical successes for cancer immunotherapy. However, its application has been impeded by the “cold” tumor microenvironment. Here, weak acidity-responsive nanoparticles co-loaded with CRISPR/Cas9 and paclitaxel (PTX) with the ability to convert “cold” tumor into “hot” tumor are reported. The nanoparticles exhibited high cargo packaging capacity, superior transfection efficiency, well biocompatibility, and effective tumor accumulation. The CRISPR/Cas9 encapsulated in nanoparticles could specifically knock out cyclin-dependent kinase 5 gene to significantly attenuate the expression of programmed death-ligand 1 on tumor cells. More importantly, PTX co-delivered in nanoparticles could significantly induce immunogenic cell death, reduce regulatory T lymphocytes, repolarize tumor-associated macrophages, and enhance antitumor immunity. Therefore, the nanoparticles could effectively convert cold tumor into hot tumor, achieve effective tumor growth inhibition, and prolong overall survival from 16 to 36 days. This research provided a referable strategy for the development of combinatorial immunotherapy and chemotherapy.
研究领域:
癌症免疫治疗
·
纳米技术
·
基因编辑
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2024
·
IF 18.5
Qian Cheng,Xingping Quan,Ruifeng Luo,Zhiqing Yang,Junyan Li,Ziyi Wang,Yonghua Zhao,Chunhai Fan,Ruibing Wang
Glucose is an important energy source for living cells. Particularly, most tumor cells use glycolysis to harness energy for their fast growth, invasion and metastasis even under aerobic conditions. Thus, reduction of the glucose level in cancer can lead to suppression of tumor growth. Here, macrophage membrane dressed yeast, Trojan M-yeast, is developed, via coating the surface of yeast with macrophage membrane, for targeted accumulation and suppression of tumor by glucose starvation. Due to the inflammatory homing effects of macrophage membrane, M-yeast efficiently target and colonize in the inflammatory tumor site, where they compete with tumor cells for glucose consumption, thereby disrupting glycolysis of cancer cells, resulting in the reduction of lactate accumulation and reversal of the acidosis of tumor microenvironment. Subsequently, the apoptotic tumor cells and yeast promote dendritic cell maturation, increase tumor-infiltrating cytotoxic T lymphocytes. Meanwhile, ethanol and acetaldehyde produced by yeast metabolism of glucose can re-polarize tumor associated macrophages (TAMs) to the anti-tumor phenotype (M1), thus reprogramming the tumor immunosuppressive microenvironment, leading to synergistic tumor suppression together with glucose starvation, which is different from traditional chemotherapy and immunotherapy. M-yeast exhibits promising targeted cancer therapy with a decent safety profile. This work may provide new insights as well as a new paradigm for yeast-based cancer therapy.
研究领域:
癌症治疗
·
免疫学
·
生物技术
·
细胞生物学
✓ 已验证
产品关联
DOI
高影响因子
Scientific Reports
·
2025
·Vol. 15
·期 1
·1-13
·
IF 3.9
Meng Zhuo-Nan,Chen Jian-Yuan,Yu Chong,Zheng Ai-hong,Reddy O. Sreekanth,Liu Kai-Yan,Su Yong-Rui,Zhang Shi-Tai,Wang Yin-Shuang,Gu Hang-Yu,Wang Fu-Wei,Xu Song-Cheng,Sun Li-Tao,Chen Bing-Chen,Lai Wing-Fu,Wu Guo-Qing,Zhang Da-Hong
Surgical resection of the tumor remains the preferred treatment for most solid tumors at an early stage, however, residual tumor cells after surgical resection poses a considerable obstacle in cancer treatment. Here, we developed a gel carrier using a cellulose-based gel-forming polymer (CT) combined with gelatin sponge (GS) to fill the resection cavity and delay postoperative residual tumor growth. The fabricated gel exhibited a porous nature along with gradual swelling and erosion over time. Curcumin (Cur) and apatinib (Apa) were loaded into CT gel (CT-CA), and a sustained release behavior was observed at pH 7.4 and 6.4 at 37 °C. The preclinical studies indicated that the mouse weight and tissue exhibited no apparent change after administration of the GS-CT compared with the control. The in vivo fluorescence images showed that GS-CT has the capability to regulate the release of Cur and Apa, facilitating the accumulation of these two agents at the surgical tumor site. Moreover, GS-CT loaded Cur and Apa (GS-CT-CA) delayed postoperative residual tumor growth in intraperitoneal and subcutaneous postoperative mouse models. These findings demonstrated that our gel carrier system significantly prevents postoperative residual tumor growth because of enhanced drug accumulation and sustained drug release at the tumor site.
研究领域:
肿瘤学
·
药剂学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2015
·
IF 3.65
Yanyun Xu,Haijing Meng,Fang Du,Wei Lu,Shiyuan Liu,Jin Huang,Jiahui Yu
Our recent publication showed that VES-dFdC nanocapsules in pure water could be obtained via the self-assembling of VES-dFdC prodrug synthesized by coupling gemcitabine (dFdC) with vitamin E succinate (VES). To prepare the intravenous injection nanoformulation, we present here a novel strategy to improve the stability and drug concentration of VES-dFdC nanoformulation in PBS or isotonic solution . Particularly, d -α-tocopheryl polyethylene glycol succinate (TPGS), usually used as drug solubilizer and coincidentally contains the same VES moiety as VES-dFdC prodrug and PEG chain, is selected to co-assemble with VES-dFdC prodrug. The zeta potentials of all the TPGS/VES-dFdC co-assemblies were close to 0 mV, and their particle size measured by dynamic light scattering (DLS) decreased from 113 to 36 nm with increasing TPGS/VES-dFdC molar ratios from 0.15 to 1.5. Stable colloidal suspensions were obtained without aggregates in PBS at 4 °C in one month or isotonic solution at 37 °C in one week, and the weight concentration of VES-dFdC prodrug increased from 7 to 17 mg/mL when the molar ratios of TPGS/VES-dFdC ranged from 0.5/1 to 1.5/1. The concentration of VES-dFdC prodrug was high enough to be used as intravenous injection nanoformulation in nude mice . Interestingly, along with the increase of TPGS/VES-dFdC molar ratios from 0.3/1 to 1.5/1, the morphology of TPGS/VES-dFdC co-assemblies changed from loose nanocapsule to compact micelle revealed by transmission electron microscope (TEM). Finally, the co-assembly of TPGS/VES-dFdC (TPGS/VES-dFdC: 1/1) was selected as intravenous injection nanoformulation to evaluate the antitumor activity . Compared with native dFdC, TPGS/VES-dFdC nanoformulation with 0.2 mmol/kg of dosage showed similar low toxicity in vivo , but 4.7 times high of tumor inhibition rate in nude mice with pre-established BxPC-3 tumors.
研究领域:
药学
·
肿瘤学
✓ 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）