INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2017
·Vol. 18
·期 4
·815
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IF 3.226
Zhaojun Li,Hui Huang,Lili Huang,Lianfang Du,Ying Sun,Yourong Duan
In general, atherosclerosis is considered to be a form of chronic inflammation. Dexamethasone has anti-inflammatory effects in atherosclerosis, but it was not considered for long-term administration on account of a poor pharmacokinetic profile and adverse side effects. Nanoparticles in which drugs can be dissolved, encapsulated, entrapped or chemically attached to the particle surface have abilities to incorporate dexamethasone and to be used as controlled or targeted drug delivery system. Long circulatory polymeric nanoparticles present as an assisting approach for controlled and targeted release of the encapsulated drug at the atherosclerotic site. Polymeric nanoparticles combined with ultrasound (US) are widely applied in cancer treatment due to their time applications, low cost, simplicity, and safety. However, there are few studies on atherosclerosis treatment using polymeric nanoparticles combined with US. In this study, targeted dexamethasone acetate (DA)-loaded poly (lactide-glycolide)-polyethylene glycol-cRGD (PLGA-PEG-cRGD) nanoparticles (DA-PLGA-PEG-cRGD NPs) were prepared by the emulsion-evaporation method using cRGD modified PLGA-PEG polymeric materials (PLGA-PEG-cRGD) prepared as the carrier. The average particle size of DA-PLGA-PEG-cRGD NPs was 221.6 ± 0.9 nm. Morphology of the nanoparticles was spherical and uniformly dispersed. In addition, the DA released profiles suggested that ultrasound could promote drug release from the nanocarriers and accelerate the rate of release. In vitro, the cellular uptake process of fluorescein isothiocyanate (FITC)@DA-PLGA-PEG-cRGD NPs combined with US into the damaged human umbilical vein endothelial cells (HUVECs) indicated that US promoted rapid intracellular uptake of[email protected]PLGA-PEG-cRGD NPs. The cell viability of DA-PLGA-PEG-cRGD NPs combined with US reached 91.9% ± 0.2%, which demonstrated that DA-PLGA-PEG-cRGD NPs combined with US had a positive therapeutic effect on damaged HUVECs. Overall, DA-PLGA-PEG-cRGD NPs in combination with US may provide a promising drug delivery system to enhance the therapeutic effects of these chemotherapeutics at the cellular level.Keywords:dexamethasone acetate;polymeric nanoparticles;ultrasound;atherosclerosis;polypeptide targeting
研究领域:
药学
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心血管病学
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PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2023
·
IF 10.8
Xiaomei Liang,Yulu Yang,Chuanqing Huang,Zhibin Ye,Wujiang Lai,Jiamao Luo,Xiaoxuan Li,Xiao Yi,Jun-Bing Fan,Ying Wang,Yifeng Wang
Resistance to the chemotherapeutic agent cisplatin (DDP) is the primary reason for invalid chemotherapy of ovarian cancer. Given the complex mechanisms underlying chemo-resistance, the design of combination therapies based on blocking multiple mechanisms is a rationale to synergistically elevate therapeutic effect for effectively overcoming cancer chemo-resistance. Herein, we demonstrated a multifunctional nanoparticle ( [email protected] ), which could simultaneously co-deliver DDP and Olaparib (Ola, DNA damage repair inhibitor) using targeted ligand cRGD peptide modified with heparin (HR) as nanocarrier, enabling the concurrent tackling of multiple resistance mechanisms to effectively inhibit the growth and metastasis of DDP-resistant ovarian cancer. In combination strategy, heparin could suppress the function of multidrug resistance-associated protein 2 (MRP2) and P-glycoprotein (P-gp) to promote the intracellular accumulation of DDP and Ola by specifically binding with heparanase (HPSE) to down-regulate PI3K/AKT/mTOR signaling pathway, and simultaneously served as a carrier combined with Ola to synergistically enhance the anti-proliferation ability of DDP for resistant ovarian cancer, thus achieving great therapeutic efficacy. Our [email protected] could provide a simple and multifunctional combination strategy to trigger an anticipated cascading effect, thus effectively overcoming the chemo-resistance of ovarian cancer.
研究领域:
药学科学
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癌症研究
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纳米技术
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药物递送系统
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PubMed
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Materials Science & Engineering C-Materials for Biological Applications
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2021
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IF 7.328
Wenquan Huang,Yuehua Deng,Liping Ye,Qiuling Xie,Yanbin Jiang
Poor safety and effectiveness is an outstanding challenge in the preparation of drug delivery systems (DDS) for cancer treatment. The pursuit of the high curative effect will inevitably increase the risk of adverse side effects. Herein, a bio-safe DDS was constructed by combining the advantages of functional zein and Au doped mesoporous silica nanoparticles ( [email protected] 2 ) to achieve chemo-photothermal therapy. The cRGD functionalized zein (cRGD-Zein) was coated on the surface of [email protected] 2 which effectively avoided premature leakage of paclitaxel and realized sustained drug release. Meanwhile, the high hemolysis rate (107%) of [email protected] 2 had been significantly reduced to 4%. The anti-hemolysis mechanism of functionalized zein was explored to give a deeper understanding of the interaction between nanoparticles and RBCs. The results showed that the functional zein would change the protein conformation during the interaction with [email protected] 2 to protect the RBCs from the damage of [email protected] 2 . And the release rate of hemoglobin was limited by the size of RBCs membrane cracks with approximately 40 nm in width and 470 nm in length. The cell cytotoxicity and uptake assays showed that the prepared DDS exhibited low tumour cell viability (35%) and enhanced uptake performance (99.3%). This work suggested that the prepared nanoparticles could serve as a promising carrier to achieve safe and efficacious tumour therapy.
研究领域:
纳米技术
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生物医学工程
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药学
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癌症研究
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COLLOIDS AND SURFACES B-BIOINTERFACES
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2020
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IF 4.389
Yifei Wang,Wen Hu,Bomei Ding,Dawei Chen,Lifang Cheng
To improve antitumor efficiency of chemotherapy and reduce side effect, according to the physiological characteristics of tumor tissues and tumor intracellular microenvironment, a multifunctional drug delivery system with properties of long circulation, active targeting, redox and pH triggered drug release was established based on the Generation 4 polyamidoamine dendrimer (PAMAM). First, the redox cleavable disulfide bonds (S S) were introduced for linking polyethylene glycol (PEG) with PAMAM to form PAMAM-S-S-PEG (PSSP). Then cRGD peptide was applied to the PEG end of PSSP to construct RGD-PSSP conjugates. Finally, encapsulating the antitumor chemotherapy drug doxorubicin (DOX) into the hydrophobic cavity of RGD-PSSP conjugates constructed the RGD-PSSP/DOX drug delivery system. The in vitro experiments displayed that RGD-PSSP/DOX NPs showed obviously redox and pH dual sensitive drug release profile. MTT and cell uptake observation elucidated cRGD modification could increase the cytotoxicity, and promote the uptake of B16 cells and HUVEC cells both overexpressing integrin ανβ3on cell membrane. Cell uptake mechanism investigation further revealed that RGD-PSSP/DOX interacted with plasma membrane via specific recognition of cRGD peptide with integrin ανβ3, and was subsequently internalized mainly through clathrin- and caveolin-mediated endocytosis. Remarkably, RGD-PSSP/DOX presented superior anticancer activity and lower heart and kidney toxicity in vivo , which could be regarded as a potential candidate for efficient antitumor chemotherapy drug delivery.
研究领域:
药学
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化疗
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纳米医学
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癌症生物学
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生物医学工程
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高影响因子
DRUG DELIVERY
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2023
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IF 6
Xiaoyan Xu,Tianhao Zhou,Xudong Wei,Xuelian Jiang,Jiyan Cao
Although surgery-based comprehensive therapy is becoming the main approach to treat laryngeal cancer, recurrence, metastasis, radiotherapy resistance and chemotherapy tolerance are still the main causes of death in patients. Targeted inhibition of laryngeal cancer stem cells has been considered as the consensus to cure laryngeal cancer. Our previous study has confirmed proto-oncogene Bmi-1 as a key regulator for self-renewal of laryngeal cancer stem cells. Targeted knockdown of Bmi-1 gene effectively inhibited the self-renewal and differentiation of laryngeal cancer stem cells, leading to the promoted sensitivity to chemotherapy including paclitaxel. However, due to off-target effects and quick degradation of the naked Bmi-1-RNAi small RNA oligo by nuclease in body fluids, it is urgently needed to develop a tumor-targeted delivery system with a protective shell. In this study, we designed and synthesized cRGD peptide-modified chitosan-polyethylene glycol slow-release nanoparticles (mPEG-CS-cRGD/Bmi-1RNAi-PTX) containing Bmi-1RNAi siRNA oligo and paclitaxel, which showed spherical in shape, 200 nm diameter in size, low cytotoxicity, strong DNA wrapping, resistance to nuclease degradation and high transfection efficiency to cells. Functional analysis indicated significant suppression of cell proliferation and migration and induction of apoptosis by the nanocomplex in laryngeal cancer cells in vitro. By application to the mouse model with laryngeal cancer, the nanocomplex inhibited tumor growth significantly in vivo. In addition, cRGD peptide, paclitaxel and Bmi-1 siRNA in the nanoparticles showed synergistic effects to suppress laryngeal cancer stem cells. In conclusion, this study not only developed a laryngeal tumor-targeted chemotherapeutic system, but also demonstrated a Bmi-1 RNAi-based chemotherapeutic strategy to inhibit cancer stem cells, having strong potential to treat laryngeal cancer patients suffering therapy resistance and/or tumor recurrence.
研究领域:
肿瘤学
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纳米技术
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分子生物学
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药学
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PubMed
高影响因子
MOLECULAR PHARMACEUTICS
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2025
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IF 4.5
Xiaoju Zhou,Chenyuan Wang,Haojie Ke,Rui Zhang,Xiaoya Yu,Wei Li,Shi Chen,Lianrong Wang
Melanoma is one of the most common and aggressive skin malignancies with unsatisfactory treatment effects due to the serious side effects, multidrug resistance, and poor prognosis. Chemotherapeutic transdermal delivery has emerged as a highly effective and novel strategy for melanoma therapy. In this study, we chose hydrophobic 10-hydroxycamptothecin (HCPT) as a model drug and developed novel microneedle (MN) patches integrated with cRGD-modified pH-sensitive HCPT liposomes (cRGD-LP-HCPT MN patches). The approach not only enhances the drug’s solubility and stability but also allows for high targeting specificity and maximizing intracellular drug accumulation in melanoma cells. The cRGD-modified pH-sensitive HCPT liposomes (cRGD-LP-HCPT) were prepared by using a thin-film hydration-ultrasonic method. cRGD-LP-HCPT exhibited high drug encapsulation efficiency (94.78%), small size (∼102.91 nm), good stability, and a profile of a rapid drug release triggered by acidic conditions. Meanwhile, it displayed higher cytotoxic effects, with an IC50 value of 1 μg/mL, compared to HCPT or the liposomes without modification. Consequently, to facilitate the transdermal delivery of HCPT into deep tumor tissues, cRGD-LP-HCPT were assembled into water-soluble needle tips of the microneedles. The cRGD-LP-HCPT MN patches exhibited excellent mechanical properties. Successful needle penetration into the pig skin with a distribution at a depth of about 200 μm was observed. Furthermore, in contrast to the systemic distribution profile of intravenous cRGD-LP-IR780, cRGD-LP-IR780 MN patches led to highly localized and potent tumor-specific fluorescence with negligible exposure to normal tissues. Ultimately, this novel HCPT formulation exhibited significant antitumor efficiency and minimal side effects. These results demonstrated that the cRGD-LP-HCPT MN patch could be a promising drug delivery system for melanoma treatment in the clinic.
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Nanoscale
·
2014
·Vol. 6
·期 21
·12580-12590
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IF 6.739
Haiyan Chen,Bowen Li,Min Zhang,Kang Sun,Yiran Wang,Kerui Peng,Mengdi Ao,Yiran Guo,Yueqing Gu
Nanomedicine platforms that have the potential to simultaneously provide the function of molecular imaging and therapeutic treatment in one system are beneficial to address the challenges of cancer heterogeneity and adaptive resistance. In this study, Cyclic RGD peptide (cRGD), a less-expensive active tumor targeting tri-peptide, and doxorubicin (DOX), a widely used chemotherapeutic drug, were covalently attached to Ag2S quantum dots (QDs) to form the nano-conjugates Ag2S-DOX-cRGD. The optical characterization of Ag2S-DOX-cRGD manifested the maintenance of QDs fluorescence, which suggested the potential of Ag2S for monitoring intracellular and systemic drug distribution. The low biotoxicity of Ag2S QDs indicated that they are promisingly safe nanoparticles for bio-applications. Furthermore, the selective imaging and favorable tumor inhibition of the nanoconjugates were demonstrated at both cell and animal levels. These results indicated a promising future for the utilization of Ag2S QDs as a kind of multi-functional nano platform to achieve imaging-visible nano-therapeutics.
研究领域:
纳米医学
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肿瘤学
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生物材料学
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高影响因子
Biomaterials Science
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2018
·Vol. 7
·期 1
·92-103
·
IF 5.831
Huixiang Yan,Jingqin Chen,Ying Li,Yuanyuan Bai,Yunzhu Wu,Zonghai Sheng,Liang Song,Chengbo Liu,Hai Zhang
Although photoacoustic imaging combined with second near infrared (NIR II) molecular probes for tumor diagnosis has drawn tremendous attention during the past few decades, the targeted photoacoustic imaging of orthotopic hepatocellular carcinoma (HCC) still remains a challenge due to high liver vascularization and non-specificity of probes in liver tumors. Herein, we report on cyclic arginine–glycine–aspartic acid (cRGD) peptide conjugated ultrasmall CuS nanoparticles (CuS@BSA-RGD NPs) which encapsulate bovine serum albumin (BSA) and possess high optical absorption at 1064 nm. The encapsulation of BSA results in great biocompatibility of CuS@BSA-RGD NPs along with excellent photostability and physiological stability. The cRGD conjugation enables the improvement of tumor uptake of CuS@BSA-RGD NPs by virtue of its positive tumor cell targeting capability. The efficient accumulation of CuS@BSA-RGD NPs in the tumor over time after intravenous administration to orthotopic HCC bearing mice was achieved, which resulted in highly sensitive photoacoustic visualization of the tumor region. Toxicity studies indicate that CuS@BSA-RGD NPs exhibited negligible systemic toxicity in vivo. The results demonstrate that the CuS@BSA-RGD NPs might hold great promise for future imaging and diagnosis of cancer.
研究领域:
生物医学工程
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肿瘤学
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分子影像学
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PubMed
高影响因子
DRUG DELIVERY
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2025
·
IF 8.1
Liqing Chai,Xiaomin Niu,Xiaoning Li,Jingjing Han,Fugui Guo,Rongrong Wang,Xiaohui Zhou,Xiaozhou Dong,Guoshun Zhang,Ruili Wang,Guolian Ren
Malaria remains a global health crisis, with Plasmodium resistance underscoring the urgent need for advanced drug delivery strategies. To overcome the limitations of oral antimalarials, such as hepatic first-pass metabolism and insufficient drug accumulation in parasites, intestinal M cell-mediated lymphatic transport and Plasmodium-triggered drug release are effective strategies. Plasmodium parasites maintain a weakly acidic intracellular environment with high levels of glutathione (GSH). Polydopamine (PDA) remains stable in the gastrointestinal tract and degrades in the parasite’s weakly acidic, GSH-rich environment, making PDA nanoliposomes (PNLs) a promising oral delivery system for Plasmodium-responsive drug release. Additionally, cyclic arginine–glycine–aspartic acid (cRGD) can specifically target intestinal M cells, promoting lymphatic transport and thereby reducing the first-pass effect. We developed cRGD- and PDA-modified nanoliposomes (cRPNLs) to address the challenges associated with oral administration and loaded them with a disulfide bond (–SS–)-modified dihydroartemisinin (DHA) prodrug (DSSC) to simultaneously deplete GSH and induce lethal oxidative stress, thereby offering an enhanced antimalarial mechanism. In vitro, cRPNLs exhibited pH- and GSH-responsive DHA release. Ex vivo fluorescent imaging confirmed that cRPNLs targeted Peyer’s patches with minimal distribution in the liver. Crucially, both PNLs and cRPNLs reduced GSH levels in infected erythrocytes and elevated ROS by 2.0-fold, outperforming unmodified DHA. Pharmacokinetic and in vivo antimalarial pharmacodynamic studies revealed that cRPNLs exhibited significantly higher exposure and Plasmodium inhibition rates compared to PNLs and free DHA. These results highlight cRPNLs as a potent oral nanoplatform that combines M cell-mediated lymphatic uptake with parasite-triggered drug release, significantly improving antimalarial efficacy.
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Polymer Chemistry
·
2019
·Vol. 11
·期 4
·889-899
·
IF 4.76
Chunhui Gao,Yinghua Zhang,Yan Zhang,Shaoyong Li,Xinlin Yang,Yan Chen,Jingwei Fu,Yinsong Wang,Xiaoying Yang
Among all X-ray tumor diagnostic imaging modalities, computed tomography (CT) has been most commonly used owing to its high spatial resolution and high detection efficiency. In order to achieve enhanced CT imaging on tumors, methacrylated iopamidol based polymer nanoparticles with disulfide bond crosslinking were prepared and then surface-modified with a cyclo[Arg-Gly-Asp-(D-Phe)-Cys] (cRGD) peptide through the linkages of poly(ethylene glycol) (PEG). The resultant poly(methacrylated iopamidol)-polyethylene glycol-cRGD (PMAI-PEG-RGD) nanoparticles were well-dispersed and had a relatively high X-ray attenuation coefficient. Compared to the nanoparticles without the modification of cRGD, PMAI-PEG-RGD nanoparticles showed specific uptake by 4T1 cells that over-express αvβ3 integrin. After being intravenously injected into 4T1 tumor-bearing mice, PMAI-PEG-RGD nanoparticles reached the tumor and further accumulated there efficiently, thus greatly enhancing the contrast of tumor CT imaging. In summary, PMAI-PEG-RGD nanoparticles have great potential to be used as a novel CT contrast agent for breast cancer-targeted imaging.
研究领域:
医学成像
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纳米技术
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癌症研究
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药学
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高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2026
·
IF 15
Deng Xu,Xie Xixiang,Zhou Xing,Jiang Lanfang,Zhu Tao,Su Rixiang,Chen Chunmei,Chen Wan,Chen Chunxia
The therapeutic efficacy of ischemic stroke (IS) treatment is severely limited by insufficient accumulation of therapeutic agents within ischemic lesions and persistent secondary injury after ischemia–reperfusion. Herein, we report a cRGD-functionalized exosome-based nanoplatform that enhances ischemic lesion-associated accumulation and antioxidative neuroprotection for the treatment of IS. Neural stem cell-derived exosomes were functionalized with cyclic RGD peptides (cRGD) and subsequently loaded with Mn₃O₄ nanoparticles to construct a hybrid nanosystem (cRGD-Exo@Mn₃O₄). The engineered exosomes preserve intrinsic brain tropism, while cRGD modification promotes preferential accumulation in ischemic regions, potentially through interaction with α v β 3 integrin that is upregulated in ischemic lesions. The incorporated Mn₃O₄ nanoparticles confer robust reactive oxygen species (ROS) scavenging capability, thereby mitigating oxidative stress in ischemic microenvironments. In vitro and in vivo studies demonstrate that cRGD-Exo@Mn₃O₄ exhibits enhanced accumulation in ischemic regions compared with non-modified counterparts. The nanosystem effectively attenuates oxidative stress and neuroinflammation, leading to reduced infarct volume, alleviation of cerebral edema, and improved neurological function in MCAO/R mice. Mechanistically, transcriptomic analysis suggests that the therapeutic effects are associated with modulation of inflammation-and cell death-related pathways, including suppression of the RIPK1/RIPK3/MLKL signaling cascade. Collectively, this study presents a rationally designed exosome-based nanoplatform integrating ischemic lesion-associated accumulation with ROS-scavenging capability. Graphical abstract
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CHEMICAL ENGINEERING JOURNAL
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2026
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IF 12.5
Haiyang Wang,Le Guo,Jiaxing Li,Chi Zhang,Yuxiang Gao,Jiaqi Ma,Jiabao Xiong,Siyu Huang,Qinfen Wu,Jingtao Wang,Yaqi Cui,Biao Dong,Nuernisha Alifu
cRGD-modified ITC NPs target αvβ3 integrin for BBB/BTB traversal in GBM. • NIR-triggered ITC NPs combine TMZ chemotherapy and phototherapy. • ITC NPs generate NO in situ to improve perfusion and modulate resistance. • NIR-II fluorescence imaging and LSCI enable GBM diagnosis and perfusion monitoring. Glioblastoma (GBM) remains one of the most lethal brain malignancies, largely due to the blood-brain barrier (BBB) and the pathologically heterogeneous blood-tumor barrier (BTB), which severely restrict drug delivery. To achieve targeted BBB/BTB traversal, we developed cRGD-modified ICG/TMZ@Lips nanoparticles (ITC NPs). The nanoplatform actively targets αvβ3 integrin overexpressed on tumor endothelial cells and GBM cells, thereby promoting receptor-mediated transport and tumor penetration. Under near-infrared (NIR) irradiation, ITC NPs trigger temozolomide (TMZ) release and photo-responsive NO-associated effects. These effects are accompanied by heat shock protein 70 (HSP70) downregulation and modulation of resistance-related pathways, which may contribute to enhanced chemosensitivity. Furthermore, we integrated near-infrared II (NIR-II) fluorescence imaging with laser speckle contrast imaging (LSCI) for real-time GBM diagnosis and perfusion monitoring. To the best of our knowledge, among existing BBB/BTB traversal strategies, this is the first study to apply cRGD peptide for specific and efficient BBB/BTB penetration in GBM therapy. This strategy directly addresses the fundamental limitations imposed by the heterogeneous and efflux-active BTB, offering a precise nanomedicine approach for improved therapeutic outcomes. Download: Download high-res image (353KB) Download: Download full-size image
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