International Journal of Nanomedicine
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2022
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IF 7.033
Cunqing Kong,Banghao Xu,Guanhua Qiu,Meng Wei,Mengqi Zhang,Shengxian Bao,Jiali Tang,Lequn Li,JunJie Liu
Introduction Photoimmunotherapy is a breakthrough treatment for malignant tumors. Its uniqueness is that it uses antibody mediated targeted delivery to achieve high tumor specificity and uses laser-activated biophysical mechanism to accurately induce the rapid death of cancer cells and avoid damaging the surrounding normal tissues. Methods In this paper, an iron-based micelle was designed to encapsulate the photothermal agent indocyanine green (ICG) and a cyclic tripeptide of arginine-glycine-aspartic acid (cRGD) as targeted multifunctional ICG@SANPs-cRGD nanoparticles for combined photothermal/photodynamic/immune therapy of breast cancer. Results The experimental results show that ICG@SANPs-cRGD nanoparticles have good biocompatibility and photothermal conversion ability. Photothermal therapy (PTT) and photodynamic therapy (PDT) based on ICG@SANPs-cRGD can not only inhibit the proliferation, invasion and migration of tumor cells, but also directly kill tumor cells by inducing apoptosis or necrosis. Dual-mode fluorescence light (FL) and magnetic resonance imaging (MRI) imaging in mice confirmed the selective accumulation at tumor sites and imaging ability of ICG@SANPs-cRGD. PTT/PDT combined with Anti-PD-L1 immunotherapy based on ICG@SANPs-cRGD mediated the immunogenic cell death (ICD) of tumor cells by regulating the expression of immune-related indicators and activated the body's immune response mechanism, which enhanced the immunotherapy effect of immune checkpoint block (ICB). PTT/PDT combined with Anti-PD-L1 therapy not only prevented the progression of the primary tumor but also inhibited the distant metastasis of the tumor. Discussion This study explores the biomedical application of PTT/PDT combined with Anti-PD-L1 based on ICG@SANPs-cRGD nanomaterials for breast cancer treatment and demonstrates the potential of ICG@SANPs-cRGD as a multifunctional therapeutic platform for future cancer therapy.
研究领域:
癌症治疗
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纳米技术
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免疫学
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生物医学工程
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2024
·Vol. 22
·期 1
·1-17
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IF 10.6
Wang Hui,Tang Cui,Xiang Yuxia,Zou Chan,Hu Jianming,Yang Guoping,Zhou Wenhu
Thrombotic diseases impose a significant global health burden, and conventional drug-based thrombolytic therapies are encumbered by the risk of bleeding complications. In this study, we introduce a novel drug-free nanomedicine founded on tea polyphenols nanoparticles (TPNs), which exhibits multifaceted capabilities for localized photothermal thrombolysis. TPNs were synthesized through a one-pot process under mild conditions, deriving from the monomeric epigallocatechin-3-gallate (EGCG). Within this process, indocyanine green (ICG) was effectively encapsulated, exploiting multiple intermolecular interactions between EGCG and ICG. While both TPNs and ICG inherently possessed photothermal potential, their synergy significantly enhanced photothermal conversion and stability. Furthermore, the nanomedicine was functionalized with cRGD for targeted delivery to activated platelets within thrombus sites, eliciting robust thrombolysis upon laser irradiation across diverse thrombus types. Importantly, the nanomedicine’s potent free radical scavenging abilities concurrently mitigated vascular inflammation, thus diminishing the risk of disease recurrence. In summary, this highly biocompatible multifunctional nanomaterial holds promise as a comprehensive approach that combines thrombolysis with anti-inflammatory actions, offering precision in thrombosis treatment.
研究领域:
纳米医学
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血栓治疗
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光热疗法
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炎症研究
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
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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
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2023
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IF 8
Zhenyu Chen,Zhongbing Liu,Shuzao Wang,Cai Cheng,Xiaoduan Sun,Zerong Liu,Jun Wei,Jun Jiang,Huaqi Lan,Meiling Zhou,Pei Jing,Yan Lin,Xiangyu Zhou,Zhirong Zhong
Background Flurbiprofen axetil (FA) is a non-steroidal anti-inflammatory drug with good analgesic and anti-inflammatory effects. However, it suffers from poor solubility, short circulation time, and off-target binding profile, which significantly limit its clinical application. Here, we loaded FA into stealth lipid microspheres modified with the arginine-glycine-aspartic acid (RGD) peptide (cRGD-FA-SLM), and examined the therapeutic potential of the resulting platform for the treatment of rheumatoid arthritis (RA).Methods cRGD-FA-SLM was prepared by high pressure homogenization, and its toxicity and uptake by macrophages were examined using cultures of RAW264.7 cells. Hemolysis and hepatotoxicity tests were performed to assess the safety of the developed platform, while its pharmacokinetics, biodistribution, and therapeutic efficacy were investigated in a collagen-induced arthritis rat model.Results cRGD-FA-SLM showed homogeneous spherical morphology and efficient encapsulation of FA. The developed platform was non-toxic to normal macrophages and was selectively internalized by lipopolysaccharide-activated macrophages in vitro, while it distributed mainly to arthritic joints and significantly prolonged FA in circulation in vivo. cRGD-FA-SLM also significantly reduced the expression of prostaglandin E2 and alleviated joint edema and bone erosion, showing prolonged analgesic effects in arthritic rats.Conclusion cRGD-FA-SLM shows good inflammation-targeting ability and prolongs drug circulation in vivo, suggesting promise as an anti-inflammatory and analgesic agent for targeted RA treatment.
研究领域:
药学
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纳米技术
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免疫学
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药理学
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风湿病学
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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
Le Guo,Yi Zhou,Jiayi Ding,Jiabao Xiong,Lijun Zhu,Siyiti Amuti,Chi Zhang,Zhong Du,Xueliang Zhang,Biao Dong,Nuernisha Alifu
The integration of photothermal and near-infrared (NIR) imaging capabilities of indocyanine green (ICG) small molecules has attracted considerable attention in tumor diagnosis and treatment. However, the abnormal upregulation of cellular heat shock proteins (HSPs) induced by photothermal therapy (PTT) enhances cellular heat resistance, thereby severely affecting the efficacy of PTT. In this study, to address the impact of HSPs on the efficacy of PTT while obtaining high-quality NIR fluorescence imaging in the NIR region, we designed a targeted peptide@ICG nanofluorescent probe encapsulated in liposomes. The introduced cRGD targeting peptide not only possesses tumor-targeting capabilities but also features LA as the last amino acid in the targeting peptide, which can generate nitric oxide (NO) under reactive oxygen species (ROS) triggering. It can happen under 808 nm single-light source NIR light, and the guanidine group in the peptide decomposes and combines with singlet oxygen molecules to generate NO gas molecules, thereby exerting an elevated photothermal effect by inhibiting the expression of HSP70. In addition, the nanoprobes enable deep imaging and treatment of glioma in situ and can be combined with a laser speckle contrast imaging (LSCI) system for multimodal imaging. This composite probe demonstrates synergistic tumor therapeutic effects of photodynamic therapy (PDT), PTT, and gas therapy, offering a promising strategy for cancer treatment.
研究领域:
癌症治疗
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生物医学工程
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纳米技术
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分子成像
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2020
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IF 10.652
Bo Li,Qian Zhou,Haiyang Wang,Yongchao Zha,Peilian Zheng,Tong Yang,Dong Ma,Lin Qiu,Ximing Xu,Ye Hu,Anna Roig,Siming Yu,Wei Xue
Triple-negative breast cancer (TNBC) is a type of highly aggressive cancer that is hard to be cured by the commonly used chemotherapy, mainly due to the lack of effective tumor targeting ability of the current drugs and TNBC drug resistance. Therefore, development of novel strategies for precise and high-efficient therapy of TNBCs is urgently needed. In the present work, a multifunctional magnetic gold nanoheterostructure with photosensitizer Ce6 loading ( [email protected] ) was designed and synthesized for synergistic photothermal and photodynamic therapy (PTT/PDT) of TNBC. To improve the tumor targeting ability, cRGD and TPP cationic molecule, which can specifically target α v β 3 integrin of cancer cell membrane and mitochondria, respectively, were functionalized on the nanosystem obtaining [email protected] @RT. In vitro and in vivo fluorescent imaging demonstrated that cRGD and TPP functionalization largely enhanced the delivery-efficiency of [email protected] @RT into TNBC cells and tumors. Under 880 nm and 660 nm laser irradiations, [email protected] @RT exhibited strong hyperthermia effect and ROS generating ability, which exerted a synergistic anti-TNBC effect by completely suppressed the tumor growth of the nude mice model. Moreover, by integrating superparamagnetic and near infrared light absorption properties into a single nanocomposite , [email protected] @RT was proved to be able to realize magnetic resonance , X-ray computed tomography and photoacoustic tri-modal imaging of in vivo tumors. In all, we provide a novel strategy for precise delivery of functional nanosystems to TNBC tumors to achieve more satisfying treating outcome.
研究领域:
纳米技术
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癌症治疗
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医学成像
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材料科学
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产品关联
DOI
高影响因子
BIOMATERIALS
·
2017
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IF 8.402
Na Zhao,Baoyan Wu,Xianglong Hu,Da Xing
Stimuli-responsive nanoparticles with multiple therapeutic/diagnostic functions are highly desirable for effective tumor treatment. Herein novel caspase-3 responsive functionalized upconversion nanoparticles (CFUNs) were fabricated with three-in-one functional integration: near-infrared (NIR) triggered photodynamic damage along with caspase-3 activation, subsequent caspase-3 responsive drug release, and cascade chemotherapeutic activation. CFUNs were formulated from the self-assembly of caspase-3 responsive doxorubicin (DOX) prodrug tethered with DEVD peptide (DEVD-DOX), upconversion nanoparticles (UCNP), a photosensitizer (pyropheophorbide-a methyl ester, MPPa), and tumor-targeting cRGD-PEG-DSPE to afford multifunctional CFUNs, MPPa/UCNP-DEVD-DOX/cRGD. Upon cellular uptake and NIR irradiation, the visible light emission of UCNP could excite MPPa to produce reactive oxygen species for photodynamic therapy (PDT) along with the activation of caspase-3, which further cleaved DEVD peptide to release DOX within tumor cells, thus accomplishing NIR-triggered PDT and cascade chemotherapy. CFUNs presented silent therapeutic potency and negligible cytotoxicity in the dark, whereas in vitro and in vivo experiments demonstrated the NIR-triggered cascade therapeutic activation and tumor inhibition due to consecutive PDT and chemotherapy. Current NIR-activated cascade tumor therapy with two distinct mechanisms is significantly favorable to overcome multidrug resistance and tumor heterogeneity for persistent tumor treatment.
研究领域:
纳米技术
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癌症治疗
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药学
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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
BIOMATERIALS
·
2021
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IF 12.479
Hong Wen,Yang Fei,Ruisi Cai,Xuemei Yao,Yanan Li,Xuan Wang,Chencheng Xue,Yan Hu,Menghuan Li,Zhong Luo
Metformin is a clinically-approved anti-diabetic drug with emerging antitumor potential, but its antitumor activity is highly susceptible to local glucose abundance. Herein, we construct a nanotherapeutic platform based on biocompatible constituents to sensitize tumor cells for metformin therapy via cooperative glucose starvation. The nanoplatform was synthesized through the spontaneous biomineralization of glucose oxidase (GOx) and metformin in amorphous calcium phosphate nanosubstrate, which was further modified with polyethylene glycol and cRGD ligands. This biomineralized nanosystem could efficiently deliver the therapeutic payloads to tumor cells in a targeted and bioresponsive manner. Here GOx could catalyze the oxidation of glucose into gluconic acid and H 2 O 2 , thus depleting the glucose in tumor intracellular compartment while accelerating the release of the entrapped therapeutic payloads. The selective glucose deprivation would not only disrupt tumor energy metabolism, but also upregulate the PP2A regulatory subunit B56δ and sensitize tumor cells to the metformin-induced CIP2A inhibition, leading to efficient apoptosis induction via PP2A-GSK3β-MCL-1 axis with negligible side effects. This study may offer new avenues for targeted tumor therapy in the clinical context.
研究领域:
纳米医学
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癌症治疗
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药学
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生物技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2024
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IF 6.9
Yufei Pan,Yuejie Zhu,Yuan Ma,Jiamei Hong,Wenting Zhao,Yujing Gao,Jing Guan,Runan Ren,Qi Zhang,Jing Yu,Zhu Guan,Zhenjun Yang
Nucleic acid drugs are attracting significant attention as prospective therapeutics. However, their efficacy is hindered by challenges in penetrating cell membranes and reaching target tissues, limiting their applications. Nucleotidyl lipids, with their specific intermolecular interactions such as H-bonding and π-π stacking, offer a promising solution as gene delivery vehicles. In this study, a novel series of nucleotide-based amphiphiles were synthesized. These lipid molecules possess the ability to self-assemble into spherical vesicles of appropriate size and zeta potential in aqueous solution. Furthermore, their complexes with oligonucleotides demonstrated favorable biocompatibility and exhibited antiproliferative effects against a broad range of cancer cells. Additionally, when combined with the cationic lipid CLD, these complexes displayed promising in vitro performance and in vivo efficacy. By incorporating DSPE-PEGylated cRGD into the formulation, targeted accumulation of siG12D in pancreatic cancer cells increased from approximately 6% to 18%, leading to effective treatment outcomes (intravenous administration, 1 mg/kg). This finding holds significant importance for the liposomal delivery of nucleic acid drugs to extrahepatic tissues.
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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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2023
·
IF 11.2
Zhechang Chen,Caijie Yuan,Yaxin Ye,Bitao Lu,Enling Hu,Fei Lu,Kun Yu,Ruiqi Xie,Guangqian Lan
Arterial thrombosis is a critical thrombotic disease that poses a significant threat to human health. However, the existing clinical treatment of arterial thrombosis lacks effective targeting and precise drug release capability. In this study, we developed a system for targeted delivery and on-demand release in arterial thrombosis treatment. The carrier was constructed using chitosan (CS) and fucoidan (Fu) through layer-by-layer assembly, with subsequent surface modification using cRGD peptide. Upon encapsulation of urokinase-type plasminogen activator (uPA), the resulting therapeutic drug delivery system, uPA-CS/Fu@cRGD, demonstrated dual-targeting abilities towards P-selectin and αIIbβ3, as well as pH and platelet-responsive release properties. Importantly, we have demonstrated that the dual targeting effect exhibits higher targeting efficiency at shear rates simulating thrombosed arterial conditions (1800 s −1 ) compared to single targeting for the first time. In the mouse common iliac artery model, uPA-CS/Fu@cRGD exhibited great thrombolytic capability while promoting the down-regulation of coagulation factors (FXa and PAI-1) and inflammatory factors (TNF-α and IL-6), thus improving the thrombus microenvironment and exerting potential in preventing re-occlusion. Our dual-target and dual-responsive, fucoidan-based macrovesicle represent a promising platform for advanced drug target delivery applications, with potential to prevent coagulation tendencies as well as improving thrombolytic and reducing the risk of re-occlusion.
研究领域:
药学
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生物医学工程
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血栓研究
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2022
·
IF 5.364
Qiyao Yang,Qi Dai,Xiaoyan Bao,Yi Zhou,Yiying Lu,Haiqing Zhong,Linjie Wu,Yinglu Guo,Lihong Liu,Xin Tan,Yiyi Xia,Min Han,Qichun Wei
Boron neutron capture therapy (BNCT) is becoming a promising radiation treatment technique dealing with tumors due to its cellular targeting specificity. In this article, based on the biocompatible chitosan oligosaccharide (COS), we designed a boron delivery system using carborane (CB) as a boron drug with cRGD peptide modification and paclitaxel (PTX) loaded in the hydrophobic core. The nanoparticles (cRGD-COS-CB/PTX) realized the boron delivery into tumor sites with an enhanced permeability and retention (EPR) effect and an active targeting effect achieved by the cRGD–integrin interaction on the surface of tumor cells. The uniform spherical nanoparticles can be selectively taken by hepatoma cells rather than normal hepatocytes. In vivo experiments showed that the nanoparticles had a targeting effect on tumor sites in both subcutaneous and orthotopic tumor models, which was an encouraging result for radiotherapy for liver cancer. To sum up, the nanoparticles we produced proved to be promising dual-functionalized nanoparticles for radiotherapy and chemotherapy.
研究领域:
癌症研究
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纳米技术
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放射治疗
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药学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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）