ACS Applied Materials & Interfaces
·
2025
·
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
·
肿瘤学
·
药物递送系统
·
光动力疗法
·
光热疗法
·
分子成像
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2024
·
IF 5.6
Zhou Xiaosong,Guo Min,Wang Zongliang,Wang Yu,Zhang Peibiao
Bioactive microspheres coated with acellular matrix (aECM) have received extensive attention in bone tissue engineering. In this work, biomimetic microspheres with different aECM ratios, uniform size and controllable size were prepared easily by blending natural porcine dermal aECM and poly (lactic-co-glycolic acid) (PLGA) using electrohydrodynamic spraying and solidification actuated by solvent extraction (ESASE) method. In this work, the appropriate polymer concentration and preparation voltage were investigated, and the surface morphology of the microspheres were observed by scanning electron microscope. Sirius red was used to visualize aECM exposure on the surface of the microspheres. The in vitro and in vivo experiments was carried out to evaluate the bioactivity and osteogenic properties of the microspheres. The results showed that the morphology and size of PLGA microspheres had little influence on the aECM blending. In vitro experiments showed that the higher the content of aECM, the better the cell adhesion performance. In vivo, rat calvarial defect models were observed and characterized at 4 and 8 weeks postoperatively, and the values of BV/TV of 50aECM/PLGA were 47.57 ± 1.14% and 72.92 ± 2.19%, respectively. The results showed that the skull healing effect was better in aECM-containing microspheres. In conclusion, aECM/PLGA composite microspheres can increase cell adhesion performance through the addition of aECM. Moreover, in vivo experiments have proved that aECM/PLGA microspheres is beneficial to bone repair, which means the aECM/PLGA microspheres is a promising bone tissue engineering material.
研究领域:
组织工程
·
生物材料
·
生物医学工程
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2014
·
IF 8.312
Hao Ren,Min Han,Jing Zhou,Ze-Feng Zheng,Ping Lu,Jun-Juan Wang,Jia-Qiu Wang,Qi-Jiang Mao,Jian-Qing Gao,Hong Wei Ouyang
The cell-cycle inhibitor flavopiridol has been shown to improve recovery from spinal cord injury in animal models . However, the systemic dose of flavopiridol has side-effects and the mechanism of action is not clear. This study aimed to develop a strategy for the local delivery of flavopiridol and investigate its mechanisms of action. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) were used for the sustained delivery of flavopiridol. The spinal cord was right-hemisectioned and NPs were delivered into the injury site. Transparent spinal cord technology was used for the three-dimensional observation of anterograde tracing. The results showed that flavopiridol NPs had a sustained release of up to 3 days in vitro . Flavopiridol NPs significantly decreased inflammatory factor synthesis by astrocytes, including TNF-α, IL-1β, and IL-6, while the IL-10 expression was elevated. In vivo study demonstrated that flavopiridol NPs decreased cell-cycle activation, inflammatory expression and glial scarring, and facilitated neuronal survival and regeneration. The cavitation volume was decreased by ∼90%. Administration of flavopiridol NPs also improved the motor recovery of injured animals. These findings demonstrated that local delivery of flavopiridol in PLGA NPs improves recovery from spinal cord injury by inhibiting astrocyte growth and inflammatory factor synthesis.
研究领域:
神经科学
·
药理学
·
纳米医学
✓ 已验证
DOI
PubMed
高影响因子
Nanoscale
·
2024
·
IF 5.8
Pan Li,Zihe Zhai,Jiawen Fang,Ruo Wang,Weiqi Li,Beiduo Wang,Jinglei Wang,Jiaqi Zhu,Feng Bing,Qiaoling Pan,ChangYou Gao,ShaoHong Lu
Together, tumor and virus-specific tissue-resident CD8+ memory T cells (TRMs) of hepatocellular carcinoma (HCC) patients with Hepatitis B virus (HBV) infection can provide rapid frontline immune surveillance. The quantity and activity of CD8+ TRMs were correlated with the relapse-free survival of patients with improved health. However, HBV-specific CD8+ TRMs have a more exhausted phenotype and respond more actively under anti-PDL1 or PD1 treatment of HBV+HCC patients. Vaccination strategies that induce a strong and sustained CD8+ TRMs response are quite promising. Herein, a biodegradable poly(D,L-lactide-co-glycolide) microsphere and nanosphere particle (PLGA N.M.P) delivery system co-assembled by anti-PD1 antibodies (aPD1) and loaded with ovalbumin (OVA-aPD1 N.M.P) was fabricated and characterized for size (200 nm and 1 μm diameter), charge (−15 mV), and loading efficiencies of OVA (238 μg mg−1 particles) and aPD1 (40 μg mg−1 particles). OVA-aPD1 N.M.P could stimulate the maturation of BMDCs and enhance the antigen uptake and presentation by 2-fold compared to free OVA. The nanoparticles also induced the activation of macrophages (RAW 264.7) to produce a high level of cytokines, including TNF-α, IL-6 and IL-10. In vivo stimulation of mice using OVA-aPD1 N.M.P robustly enhanced IFN-γ-producing-CD8+ T cell infiltration in tumor tissues and the secretion of IgG and IgG2a/IgG1 antibodies. OVA-aPD1 N.M.P delivered OVA to increase the activation and proliferation of OVA-specific CD8+ TRMs, and its combination with anti-PD1 antibodies promoted complete tumor rejection by the reversal of tumor-infiltrating CD8+ T cell exhaustion. Thus, PLGA N.M.P could induce a strong CD8+ TRMs response, further highlighting its therapeutic potential in enhancing an antitumor immune response.
研究领域:
癌症免疫学
·
药学
·
免疫治疗
·
纳米技术
·
肿瘤生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TRANSPLANT INTERNATIONAL
·
2020
·Vol. 33
·期 4
·450-461
·
IF 3.177
Shoubao Wang,Yao Xiong,Yinmin Wang,Jingting Chen,Jun Yang,Binbin Sun
Summary Systemic immunosuppression is indispensable for vascularized composite allotransplantation (VCA). Daily administration of standard triple therapy regimen of tacrolimus (FK506), mycophenolate mofetil (MMF), and steroid has severe side effects and reduces the compliance of VCA recipients. To overcome these hurdles, FK506/MMF/prednisolone (PDNN) was loaded into PLGA microspheres (PGLA MS). A single injection of FK506/MMF/PDNN-PLGA MS significantly prolonged the survival time of allograft in a rat hind limb transplantation model with a median survival time (MST) of more than 150 days compared to 34.5 days in the group treated orally with FK506/MMF/PDNN and 11 days in the nontreatment allograft and MS control groups. Analysis of showed that FK506/MMF/PDNN-PLGA MS could maintain relatively higher plasma and tissue drug concentrations for a long time. Moreover, histopathology and flow cytometry of circulating mononuclear cells revealed significantly prolonged immunosuppression by the FK506/MMF/PDNN-PLGA MS compared with the orally given FK506/MMF/PDNN. In conclusion, a single injection of FK506/MMF/PDNN-PLGA MS may provide a new approach for long-term prevention of immune rejection in VCA.
研究领域:
移植免疫学
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2022
·
IF 6.819
Yanhai Xi,Weiheng Wang,Liang Ma,Ning Xu,Changgui Shi,Guohua Xu,Hailong He,Wenming Pan
Astragaloside (AS) has an anti-osteoporotic effect, but its poor water solubility and low bioavailability limit its application. In this study, a novel nano-carrier with bone targeting was prepared by modifying mPEG-PLGA with alendronate (AL) before incorporation into astragaloside nano-micelles (AS-AL-mPEG-PLGA) to enhance the oral bioavailability, bone targeting and anti-osteoporosis effect of AS. The release behavior of AS-AL-mPEG-PLGA in vitro was investigated via dialysis. The pharmacokinetics of AS-AL-mPEG-PLGA was studied in Sprague-Dawley (SD) rats. The cytotoxicity of AS-AL-mPEG-PLGA in vitro (via MTT method), coupled with bone targeting ability in vitro and in vivo were evaluated. The therapeutic effects of free AS and AS-AL-mPEG-PLGA (ELISA, micro-CT, H&E staining) were compared in osteoporotic rats. AS-AL-mPEG-PLGA with smaller particle size (45.3 ± 3.8 nm) and high absolute zeta potential (−23.02 ± 0.51 mV) were successfully prepared, wherein it demonstrated higher entrapment efficiency (96.16 ± 0.18%), a significant sustained-release effect for 96 h and acceptable safety within 10–200 μg/mL. AS-AL-mPEG-PLGA could enhance the hydroxyapatite affinity and bone tissue concentration of AS. The relative bioavailability of AS-AL-mPEG-PLGA was 233.90% compared with free AS. In addition, the effect of AS in reducing serum levels of bone metabolism-related indicators, restoring the bone microarchitecture and improving bone injury could be enhanced by AS-AL-mPEG-PLGA. AS-AL-mPEG-PLGA with small particle size, good stability, remarkable sustained-release effect, safety and bone targeting was successfully constructed in this experiment to potentially improve the oral bioavailability and anti-osteoporosis effect of AS. Thus, AS-AL-mPEG-PLGA may be a promising strategy to prevent and treat osteoporosis.
研究领域:
药剂学
·
药理学
·
纳米技术
·
骨生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2018
·
IF 1.883
Juan Dai,Wei Long,Zhongping Liang,Lu Wen,Fan Yang,Gang Chen
Delivery of biomacromolecular drugs into the inner ear is challenging, mainly because of their inherent instability as well as physiological and anatomical barriers. Therefore, protein-friendly, hydrogel-based delivery systems following local administration are being developed for inner ear therapy. Herein, biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) containing interferon α-2 b (IFN α-2 b) were loaded in chitosan/glycerophosphate (CS/GP)-based thermosensitive hydrogel for IFN delivery by intratympanic injection. The injectable hydrogel possessed a physiological pH and formed semi-solid gel at 37 °C, with good swelling and deswelling properties. The CS/GP hydrogel could slowly degrade as visualized by scanning electron microscopy (SEM). The presence of NPs in CS/GP gel largely influenced in vitro drug release. In the guinea pig cochlea, a 1.5- to 3-fold increase in the drug exposure time of NPs-CS/GP was found than those of the solution, NPs and IFN-loaded hydrogel. Most importantly, a prolonged residence time was attained without obvious histological changes in the inner ear. This biodegradable, injectable, and thermosensitive NPs-CS/GP system may allow longer delivery of protein drugs to the inner ear, thus may be a potential novel vehicle for inner ear therapy.
研究领域:
药学
·
生物医学工程
·
药物递送系统
·
内耳治疗
✓ 已验证
DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2024
·
IF 5.6
Chen Zhengrong,Mo Quansheng,Mo Dandan,Pei Xiaomin,Liang Anru,Cai Jinhong,Zhou Bo,Zheng Li,Li Hongmian,Yin Feiying,Zhao Jinmin
Injury caused by excess reactive oxygen species (ROS) may lead to susceptibility to bacterial infection and sustained inflammatory response, which are the major factors impeding diabetic wound healing. By utilizing optimal anti-inflammatory, antioxidant, and antibacterial biomaterials for multifunctional wound dressings is critical in clinical applications. In this study, a novel electrospun PLGA/MoS2@Pd nanofiber membrane was synthesized by encapsulating antioxidant and near-infrared (NIR) responsive MOS2@Pd nanozymes in PLGA nanofibers to form a multifunctional dressing for diabetic wound repair. With excellent biocompatibility and hemostatic ability, this novel PLGA/MoS2@Pd nanofiber membrane can effectively reduce oxidative stress damage and intracellular inflammatory factors expression in fibroblasts by scavenging ROS. Additionally, the PLGA/MoS2@Pd nanofiber membrane exhibited favourable NIR-mediated photothermal antibacterial activity in vitro, with inhibition rates of 97.14% and 97.07% against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), respectively. In a diabetic rat wound infection model, NIR-assisted PLGA/MoS2@Pd nanofiber membrane effectively inhibited bacterial growth in the wound, reduced infection-induced inflammatory response, and promoted tissue epithelialization and collagen deposition, resulting in a wound healing rate of up to 98.5% on day 14. This study highlighted the construction of a multifunctional nanofiber membrane platform and demonstrated its promising potential as a clinical dressing for diabetic wounds.
研究领域:
生物材料
·
伤口愈合
·
纳米技术
·
糖尿病
·
光热治疗
·
抗菌材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Research Express
·
2025
·Vol. 12
·期 1
·015403
·
IF 2.2
Huinan Zhang,Dongchao Ji,Kunlong Zhao,Zhuoheng Li,Shuo Yang,Peng Wang,Wenxin Cao,Yu Sun
Biomedical scaffolds are increasingly used in bone repair due to their exceptional ability to support cell growth and proliferation. This study developed a multifunctional poly(lactic-co-glycolic acid) (PLGA)/polyvinyl alcohol (PVA)/metronidazole coaxial electrospun nanofiber membrane to overcome the limitations of current bone tissue self-repair mechanisms. Optimization of the coaxial electrospinning parameters significantly improved the membrane's overall performance. Mechanical property testing revealed that the tensile strength increased from 4.304 ± 0.079 MPa to 6.915 ± 0.032 MPa as the shell layer feeding rate was increased. Drug release studies demonstrated a marked reduction in the initial burst release of metronidazole as the shell layer thickness increased. The release amount decreased from 86% to 34% by the third hour, and the release continued over the course of one week. Furthermore, the in vitro release model transitioned from first-order kinetics to Peppas-Sahlin kinetics. In vitro studies confirmed that the metronidazole-loaded coaxial fiber membrane exhibited excellent biocompatibility, antibacterial properties, and osteogenic potential. In conclusion, PLGA/PVA controlled-release nanofiber membranes loaded with antibacterial drugs offer great promise for bone tissue regeneration therapies.
研究领域:
生物医学工程
·
组织工程
·
药剂学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
Regenerative Biomaterials
·
2025
·
IF 8.1
Zhang Ting,Yu Yameng,Yuan Wei,Ren Zeqi,Cheng Yan,Wu Shuilin,Zheng Yufeng,Xia Dandan
Biodegradable Zn alloy have recently gained considerable attention for use in bone implants considering their biodegradability, attractive mechanical properties, and bioactivity. However, excessive corrosion of Zn alloy at the early stage of implantation may cause severe cytotoxicity, resulting in insufficient osseointegration, which hinders the clinical use of the Zn alloy. In this study, we designed a photothermal-controlled degradative hybrid coating as corrosion-protective barrier with the intention of preventing Zn ion burst release during the early stages of implantation and regaining the alloy's corrosion advantage later on. The coating consisting of Zeolite imidazole skeleton-encapsulated indocyanine green core-shell structured nanoparticles and polylactic coglycolic acid (ICG@ZIF-8/PLGA) on pristine Zn-0.8 (wt.%) Li (ZL) alloy. The electrochemical test results indicated that coating ZL with ICG@ZIF-8/PLGA might effectively reduce its corrosion current density (icorr) from 2.48 × 1 0 −5 A•cm−2 to 2.10 × 1 0 −8 A•cm−2. After near-infrared light irradiation, ICG@ZIF-8 heated PLGA coating to reach Tg, so that the coating was degrading, and the icorr of coated ZL alloy decreased to 2.50 × 1 0 −7 A•cm−2, thus restoring corrosion advantage. Both in vitro and in vivo investigations showed that coated ZL alloy had acceptable biocompatibility. Overall, the development of the photothermally controlled coating improved the Zn alloy's resistance to corrosion and allowed for the adjustment of the coated ZL alloy's rate of degradation through the use of 808 nm NIR laser irradiation.
研究领域:
生物医学工程
·
材料科学
·
生物材料
·
组织工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Tissue Engineering and Regenerative Medicine
·
2023
·
IF 3.6
Zhang Ying,Li Chuan,Wei Qiushi,Yuan Qiang,He Wei,Zhang Ning,Dong Yiping,Jing Zhenhao,Zhang Leilei,Wang Haibin,Cao Xiangyang
BACKGROUND: This study aimed to explore the effect of a nanomaterial-based miR-320a inhibitor sustained release system in trauma-induced osteonecrosis of the femoral head (TIONFH). METHODS: The miR-320a inhibitor-loaded polyethylene glycol (PEG)- Poly(lactic-co-glycolic acid) (PLGA)- Poly-L-lysine (PLL) nanoparticles were constructed using the double emulsion method. The TIONFH rabbit model was established to observe the effects of miR-320a inhibitor nanoparticles in vivo . Hematoxylin–eosin staining and microcomputed tomography scanning were used for bone morphology analysis. Bone marrow mesenchymal stem cells (BMSCs), derived from TIONFH rabbits, were used for in vitro experiments. Cell viability was determined using the MTT assay. RESULTS: High expression of miR-320a inhibited the osteogenic differentiation capacity of BMSCs in vitro by inhibiting the expression of the osteoblastic differentiation markers ALP and RUNX2. MiR-320a inhibitor-loaded PEG-PLGA-PLL nanoparticles were constructed with a mean loading efficiency of 1.414 ± 0.160%, and a mean encapsulation efficiency of 93.45 ± 1.24%, which released 50% of the loaded miR-320a inhibitor at day 12 and 80% on day 18. Then, inhibitor release entered the plateau. After treatment with the miR-320a inhibitor nanoparticle, the empty lacunae were decreased in the femoral head tissue of TIONFH rabbits, and the osteoblast surface/bone surface (Ob.S/BS), osteoblast number/bone perimeter (Ob.N/B.Pm), bone volume fraction, and bone mineral density increased. Additionally, the expression of osteogenic markers RUNX2 and ALP was significantly elevated in the TIONFH rabbit model. CONCLUSION: The miR-320a inhibitor-loaded PEG-PLGA-PLL nanoparticle sustained drug release system significantly contributed to bone regeneration in the TIONFH rabbit model, which might be a promising strategy for the treatment of TIONFH.
研究领域:
纳米技术
·
骨科
·
再生医学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
IF 4.8
Ningchao Luo,Lisha Ma,Ninghui Ma,Jiale Wei,Hongyan Zhang,Wanyu Jin,Yujie Li,Jingbin Shi,Yang Xiong
Triple negative breast cancer (TNBC) represents a heterogeneous subtype of breast cancer characterized by an unfavorable prognosis due to its aggressive biology. Cancer-associated adipocytes (CAAs) play an active role in tumor development, invasion and metastasis, and response to treatment by secreting various cytokines. CAAs secrete CCL2 and ADPN which significantly affect the efficacy of aPD-1 in treating breast cancer. Our recent research has demonstrated that Hesperidin, a natural phenolic compound, significantly inhibits CCL2, elevates ADPN secreted by CAAs in vitro and in vivo, remodels the immune microenvironment, and potentiates the efficacy of aPD-1 in triple-negative breast cancer. We used Oil red staining, Bodipy 493/503 staining and quantitative real-time PCR to verify the formation of CAAs. ELISA was used to detect levels of CCL2, ADPN secreted by CAAs. Changes in the number of immune cells in mouse tumor tissues were detected using flow cytometry and immunofluorescence. Our data suggest that Hesperidin PLGA nanoparticles significantly reduced CCL2 and increased ADPN secreted by CAAs, which concurrently decreased the recruitment of M2 macrophages, Tregs and MDSCs while increased the infiltration of CD8 + T cells, M1 macrophages and DCs into tumor, thus significantly potentiated the efficacy of aPD-1 in vivo. This study provides a new combined strategy for the clinical treatment of triple-negative breast cancer by interfering with CCL2, ADPN secreted by CAAs to enhance the efficacy of immunotherapy.
研究领域:
肿瘤学
·
免疫学
·
药理学
·
分子生物学
✓ 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）