INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2025
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IF 5.2
Huilian Huang,Sajid Asghar,Ling Lin,Su Chen,Chenjun Yuan,Muhui Sang,Yanyu Xiao
The combination of chemotherapy and photothermal therapy not only improves the therapeutic effect but also limits the side effects of drugs. Herein, a multi-responsive dual-modality bone-targeted drug delivery vehicle for the treatment of osteosarcoma was designed by utilizing alendronate sodium as a bone-targeting ligand for the targeted delivery of doxorubicin (DOX) loaded polydopamine nanoparticles (PDA NPs) coated with γ-polyglutamic acid (APC@PDA/DOX NPs). The average size of spherical NPs was 140.0 nm with a zeta potential of −25.63 mV. The drug loading and encapsulation efficiency were 11.63 % and 96.44 %, respectively. The constructed NPs were responsive to acidic pH, redox conditions, and near-infrared light as the drug release rate of the system reached 70 %. Cell experiments showed that APC@PDA/DOX NPs significantly enhanced cytotoxicity in mouse K7M2 osteosarcoma cells due to PDA-induced hyperthermia and DOX-induced cytotoxicity. Compared with the free DOX solution, the area under the curve of APC@PDA/DOX NPs increased by 8.52 times, iterating the significantly prolonged circulation time of NPs in vivo that manifested in higher bioavailability. The biodistribution study showed that APC@PDA/DOX NPs enacted excellent bone targeting and tumor tissue localization. In general, APC@PDA/DOX NPs may offer a feasible and effective strategy for osteosarcoma-targeted therapy.
研究领域:
药学
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肿瘤学
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纳米医学
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DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2023
·Vol. 21
·期 1
·1-19
·
IF 10.2
Xu Yanlong,Du Longhai,Han Binxu,Wang Yu,Fei Jichang,Xia Kuo,Zhai Yonghua,Yu Zuochong
Background Osteosarcoma (OS) is the most prevalent primary malignant bone tumor. However, single-agent chemotherapy exhibits limited efficacy against OS and often encounters tumor resistance. Therefore, we designed and constructed an integrated treatment strategy of photothermal therapy (PTT) combined with chemotherapy and used a surface-encapsulated platelet-osteosarcoma hybrid membrane (OPM) that enhances circulation time and enables OS-specific targeting. Results The OPM functions as a shell structure, encapsulating multiple drug-loaded nanocores (BPQDs-DOX) and controlling the release rate of doxorubicin (DOX). Moreover, near-infrared light irradiation accelerates the release of DOX, thereby extending circulation time and enabling photostimulation-responsive release. The OPM encapsulation system improves the stability of BPQDs, enhances their photothermal conversion efficiency, and augments PTT efficacy. In vitro and ex vivo experiments demonstrate that BPQDs-DOX@OPM effectively delivers drugs to tumor sites with prolonged circulation time and specific targeting, resulting in superior anti-tumor activity compared to single-agent chemotherapy. Furthermore, these experiments confirm the favorable biosafety profile of BPQDs-DOX@OPM. Conclusions Compared to single-agent chemotherapy, the combined therapy using BPQDs-DOX@OPM offers prolonged circulation time, targeted drug delivery, enhanced anti-tumor activity, and high biosafety, thereby introducing a novel approach for the clinical treatment of OS.
研究领域:
肿瘤学
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纳米技术
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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
Scientific Reports
·
2025
·Vol. 15
·期 1
·1-22
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IF 3.9
Bai Guannan,Zhao Shaobo,Chen Lushan,Zhao Manli,Chen Wenhao
Osteosarcoma (OS) is the most common bone malignancy in children and adolescents. The 5-year survival rate is only approximately 20% in patients with metastatic and recurrent OS. There is an urgent need to explore novel therapeutic targets to improve the survivorship of OS patients. It has been reported that dysfunction of programmed cell death (PCD) plays an essential role in tumor malignancy. In this study, differentially expressed PCD genes (PCD-DEGs) in OS were identified. Functional enrichment and somatic mutation analysis were performed. Then we established a novel indicator, the cell death index (CDI), to predict therapeutic interventions, immunity responses, and prognosis concerning OS. The expression of PCD genes in osteosarcoma and normal tissues was determined by immunohistochemistry assays. A total of 265 PCD-DEGs were identified in OS, with 141 genes upregulated and 124 genes downregulated. After functional enrichment and somatic mutation analysis, a final PCD-related gene signature, involving the expression levels of CLTCL1, FADS2, and PLEKHF1, demonstrated significant predictive value. A nomogram including clinical characteristics and CDI was developed, which was verified to perform well. Further investigation showed CDI was strongly correlated with immunomodulators, tumor microenvironment, and drug sensitivity in OS. Immunohistochemistry assays illustrated that FADS2, CLTCL1, and PLEKHF1 were suppressed in OS tissues. Further experiments demonstrated that FADS2 inhibits migration and invasion of osteosarcoma cells, while FADS2 induces ferroptosis collaborating with Erastin in osteosarcoma cells. In conclusion, the PCD-related gene signature proposed in this study is a practical prognostic predictor for OS patients, which can make a notable difference in the assessment of clinical outcomes.
研究领域:
肿瘤学
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分子生物学
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生物信息学
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遗传学
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病理学
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免疫学
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药理学
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产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2026
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IF 19.9
Chen Dai,Junchang Qin,Shaozhen Wu,Lanhao Shi,Xinran Song,Sisen Su,Li Ding,Hongqian Liu,Yu Chen,Chunmei Wang
Pyroelectric tumor therapy, an emerging antitumor modality relying on biocompatible pyroelectric materials to induce intertumoral catalytic reactions, has long been constrained by the requirement for conventional exogenous excitation. To address this limitation, we engineered an endogenous exothermic reaction-driven pyroelectric three-dimensional (3D) composite scaffold by screening three representative nanoparticles (CaO, CaO 2 , and MgO 2 ), which can generate significant heat at tumor sites upon exothermic reaction. We selected the highest-performing exothermic reaction CaO nanoparticles and incorporated them into a CaO/Bi 13 S 18 I 2 -loaded polycaprolactone scaffold (denoted as BC-PCL) for subsequent synergistic osteosarcoma treatment and bone regeneration. Upon tumor-site implantation, the CaO component undergoes rapid hydrolysis, releasing calcium ions (Ca 2+ ) and generating localized heat. This endogenous exothermic energy activates the pyroelectric Bi 13 S 18 I 2 phase to produce high levels of cytotoxic reactive oxygen species (ROS), enabling tumor regression while facilitating Ca 2+ -mediated scaffold-guided bone regeneration under physiological conditions. This dual-function system establishes a unique self-triggered, stepwise therapeutic cascade for efficient osteosarcoma therapy. In vitro and in vivo studies demonstrate that BC-PCL-derived ROS induces mitochondrial membrane potential depolarization and nuclear DNA damage, culminating in cancer cell apoptosis. Concurrently, the 3D-printed scaffold promotes osteogenic differentiation via Ca 2+ -mediated enhancement of cellular proliferation and osteoblastogenesis. This work introduces a paradigm-shifting strategy for osteosarcoma therapy, leveraging endogenous exothermic reactions to bypass the need for external excitation while integrating tumor eradication with bone tissue regeneration.
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DOI
高影响因子
Materials Today Bio
·
2025
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IF 10.2
Haitao Zeng,Huixiong Feng,Chong Zhang,Zhe Kang,Jianping Wu,Xingqi Zhao,Anfei Huang,Yanyang Xu,Yufeng Huang,Hongwen Xu,Ming Gong
Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents. While radiotherapy is an adjuvant treatment option for OS, particularly in cases of unresectable recurrent metastases, its efficacy remains limited. Enhancing radiosensitivity in OS cells is therefore crucial for improving treatment outcomes. Hafnium oxide, a known radiosensitizer, has demonstrated potential but its current formulation restricts its use to intratumoral administration, posing challenges for treating intraosseous tumors. The development of an intravenous formulation is thus highly desirable. Furthermore, radiotherapy resistance, driven by tumor hypoxia and an immunosuppressive microenvironment, further compromises its effectiveness. In this study, we synthesized hafnium-doped Prussian blue nanoparticles (HP) coated with a tannic acid-manganese metallophenol network (HPTM) to improve biocompatibility and enable intravenous administration. Following intravenous injection in a murine model of OS tibialis in situ tumors with lung metastases, HPTM effectively localized to the primary tumor. Within the acidic tumor microenvironment, manganese was released, activating the STING pathway and triggering anti-tumor immune responses. Moreover, near-infrared light irradiation of the Prussian blue component induced a photothermal effect, promoting apoptosis. Concurrently, under low-dose X-ray irradiation, HPTM augmented radiation energy deposition, generating reactive oxygen species and inducing DNA damage in tumor cells. This synergistic therapeutic approach significantly increased apoptosis in radiotherapy-resistant OS cells, reduced lung metastases, and suppressed primary tumor growth. These findings suggest a promising avenue for clinical translation, integrating radiosensitization, photothermal therapy, and STING pathway activation to overcome current limitations in OS radiotherapy.
研究领域:
肿瘤学
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放射生物学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2025
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IF 6.2
Yilin Wang,Sheng Zhou,Zaikai Zhuang,Xueying An,Wenjuan Wu,Bo Jiang,Chaofeng Zhang,Sehrish Manan,Peng Wang,Yongcan Jin
Lignin is a natural product that holds significant potential in tumor treatment by inhibiting tumor growth and inducing apoptosis. However, its therapeutic efficacy is often constrained by challenges such as inconsistent bioavailability, structural complexity, and potential side effects. To address these challenges, we developed a series of lignin derivatives incorporating bioactive intermediate structures to enhance their antitumor activity. These derivatives efficiently induced apoptosis in osteosarcoma (OS) through a mitochondria-dependent pathway. Notably, lignin derivatives with amino groups demonstrated pronounced cytotoxicity, while those featuring benzylamine substituents exhibited strong therapeutic effects, achieving tumor inhibition rates of up to 48%. Mechanistic investigations revealed that these derivatives disrupt mitochondrial membrane permeability, leading to cytochrome C release and subsequent activation of the apoptotic cascade. This process was characterized by the upregulation of BAX, Cyto-c, cleaved CASP3, and CASP9 and downregulation of BCL2. Both in vitro and in vivo experiments confirmed that lignin derivatives significantly inhibited OS cell proliferation while maintaining a favorable biosafety profile. These results demonstrate the therapeutic potential of lignin derivatives in OS treatment by leveraging renewable resources to synthesize bioactive intermediates. This innovative approach not only enhances therapeutic efficacy but also establishes a sustainable paradigm for pharmaceutical development.
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产品关联
DOI
PubMed
高影响因子
Small
·
2023
·Vol. 19
·期 22
·2205511
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IF 13.3
Yanling Liang,Chuanan Liao,Xinqi Guo,Guanhua Li,Xin Yang,Jing Yu,Jingping Zhong,Ying Xie,Li Zheng,Jinmin Zhao
Noble metal nanozymes hold promise in cancer therapy due to adjustable enzyme-like activities, unique physicochemical properties, etc. But catalytic activities of monometallic nanozyme are confined. In this study, 2D titanium carbide (Ti 3 C 2 T x )-supported RhRu alloy nanoclusters (RhRu/Ti 3 C 2 T x ) are prepared by a hydrothermal method and utilized for synergistic therapy of chemodynamic therapy (CDT), photodynamic therapy (PDT), and photothermal therapy (PTT) on osteosarcoma. The nanoclusters are small in size (3.6 nm), uniform in distribution, and have excellent catalase (CAT) and peroxidase (POD)-like activities. Density functional theory calculations show that there is a significant electron transfer interaction between RhRu and Ti 3 C 2 T x , which has strong adsorption to H 2 O 2 and is beneficial to enhance the enzyme-like activity. Furthermore, RhRu/Ti 3 C 2 T x nanozyme acts as both PTT agent for converting light into heat, and photosensitizer for catalyzing O 2 to 1 O 2 . With the NIR-reinforced POD- and CAT-like activity, excellent photothermal and photodynamic performance, the synergistic CDT/PDT/PTT effect of RhRu/Ti 3 C 2 T x on osteosarcoma is verified by in vitro and in vivo experiments. This study is expected to provide a new research direction for the treatment of osteosarcoma and other tumors.
研究领域:
癌症治疗
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纳米技术
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材料科学
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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
Discover Oncology
·
2025
·Vol. 16
·期 1
·1-13
·
IF 2.9
Liu Guo,Fang Yu,Li Jiamiao,Chen Zhaofei
Osteosarcoma, the most common primary bone malignancy, poses significant management challenges due to its aggressiveness and metastatic potential. This study investigates the role of anoikis-related genes, particularly phospholipase C beta 4 (PLCB4), as a prognostic biomarker in osteosarcoma. We analyzed transcriptome data from the TARGET and GSE21257 cohorts using bioinformatics tools, identifying 15 significant genes, with PLCB4 as a key marker linked to decreased survival. Our findings indicate a negative correlation between PLCB4 and immune microenvironment scores and checkpoint molecules, suggesting its impact on immunotherapy responses. Drug sensitivity analyses revealed that high PLCB4 expression correlates with lower IC50 values for several chemotherapeutic agents. In vitro experiments showed that silencing PLCB4 inhibited cell proliferation and reduced PD-L1 expression. This study underscores the critical role of PLCB4 in osteosarcoma progression and its potential as a therapeutic target, offering insights into the molecular mechanisms of osteosarcoma biology and improving prognostic accuracy and treatment strategies.
研究领域:
肿瘤学
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分子生物学
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免疫学
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产品关联
DOI
PubMed
高影响因子
MATERIALS TECHNOLOGY
·
2021
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IF 3.846
Yangfan Zheng,Jia Ye,Zhirong Zhang,Lewei Li,Hongyuan Yu,Siyi Wang,Simin Shen,Qiufang Zhang,Wei Zhang,Xiaojun Tao,Chunlian He
In this study, we grafted hydrophilic γ-polyglutamic acid (γ-PGA) with the hydrophobic drug methotrexate (MTX) to develop an amphiphilic and stimuli-responsive nanoparticles (MTX-SS-PGA NPs). The average size and zeta potential for MTX-SS-PGA NPs were 100.5 nm and −20.4 mV. In vitro drug release, the MTX cumulative release of nanoparticles within 72 h, which was more robust at 10 mM GSH (90.1%) than normal physiological environment pH 7.4 (9.8%). The disulphide bond was easily cleaved by glutathione, which subsequently led to the disintegration of the nanoparticle structure and the release of MTX. In cell studies, 10 μM MTX-SS-PGA NPs was efficient taken up into the cancer cell, released MTX in a redox-responsive manner, and exhibited cytotoxicity as potent as MTX.Moreover, 10 μM MTX-SS-PGA NPs have little side effects on normal cells. Overall, this new type of glutathione-responsive anti-osteosarcoma prodrug nanoparticles is promising for efficient drug delivery.
研究领域:
药学
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纳米技术
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癌症研究
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DOI
高影响因子
iScience
·
2024
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IF 4.6
Junjie Zheng,Lin Huang,Jinying Wang,Shiqiang Zhuo,Gaofeng Huang
Abnormal accumulation of hydrogen peroxide (H 2 O 2 ) in the tumor microenvironment is associated with altered metabolism, abnormal proliferation of tumor cells, and changes in the tumor microenvironment. Based on this phenomenon, we have developed manganese-doped zeolitic imidazolate frameworks (Mn-ZIF) nanozymes, which exhibit superior peroxidase (POD)-like activity and enhanced cytotoxicity. Inside the tumor, the H 2 O 2 is catalyzed by Mn-ZIF nanozymes through the Fenton reaction to generate more potent hydroxyl radicals (·OH), further increasing the local reactive oxygen species (ROS) levels in tumor cells and inducing tumor cell death. Meanwhile, the removal of H 2 O 2 in the tumor microenvironment reduces tumor proliferation. We have confirmed the anti-tumor effect of these particles in an in situ osteosarcoma (OS) model, providing a direction for the future design of hybrid nanozyme drug delivery systems.
研究领域:
肿瘤学
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纳米医学
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生物化学
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2025
·
IF 6.7
Siyu Lu,Jing Wu,Shuxin Lyu,Yifeng Yu,Jong Seung Kim,Ruiping Zhang,Yuling Xiao,Xuechuan Hong,Xiaodong Zeng
The integration of photoacoustic imaging (PAI) and near-infrared II (NIR-II) fluorescence imaging holds transformative potential for cancer diagnostics but faces challenges in developing high-performance dual-modal contrast agents. We report tH7@CT8, an organic nanoprobe engineered through fluorophore trimerization to address the photothermal conversion efficiency limitations of small-molecule agents. Trimerization of the [1,2,5]thiadiazolo[3,4-g]quinoxaline fluorophore derivative H7 induced aggregation, suppressing fluorescence quantum yield (0.11% vs 0.42% monomer) while amplifying PTCE to 43.1%. Encapsulation within an osteosarcoma-targeting amphiphilic matrix yielded nanoparticles (72 ± 19 nm) with 4-fold enhanced tumor uptake versus nontargeted controls. In orthotopic osteosarcoma models, tH7@CT8 enabled PAI detection and real-time NIR-II guidance with signal (tumor)-to-background ratios >12:1. This work establishes a molecular design strategy to reconcile depth-resolution trade-offs in oncology while advancing organic contrast agents toward clinical translation.
研究领域:
生物医学成像
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纳米医学
·
分子工程
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癌症诊断
·
光学成像
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2023
·
IF 5.8
Lei Zhang,Ying-Xuan Liu,Ya-Ting Yao,Tian-Jiao Zhou,Hu-Lin Jiang,Cheng-jun Li
Osteosarcoma (OS) is the most common malignant tumor of the bone that affects children and adolescents, and its treatment usually involves doxorubicin hydrochloride (DOX). However, the drug resistance and side effects caused by high-dose DOX infusion greatly hinder its therapeutic effects. To achieve efficient OS treatment with low toxicity, an injectable rhein (RH)-assisted crosslinked hydrogel ( [email protected] @DOX hydrogel, PRDH) was designed, which was prepared by loading DOX and RH into a polyvinyl alcohol (PVA) solution. The cytotoxicity assay and live/dead staining results showed that the combination of RH and DOX more effectively killed OS cells, producing excellent effects at low concentrations of DOX. The wound healing and transwell test results proved that PRDH could significantly inhibit the metastasis and invasion of OS cells. PRDH showed a long-lasting antitumor effect after injection of a single dose, significantly suppressing the proliferation and metastasis of OS and achieving the strategy of a single administration for long-term treatment. Excitingly, RH facilitated hydrogel formation by assisting with PVA crosslinking. This system provides an alternative regimen and broadens the horizon for the clinical treatment of OS.
研究领域:
药学
·
肿瘤学
·
材料科学
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产品关联
DOI
PubMed
高影响因子
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