COLLOIDS AND SURFACES B-BIOINTERFACES
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2026
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IF 5.9
Muhammad Sohail,Kai Li,Ayesha Younas,Sajid Iqbal,Xiaoxiao Chen,Baozhu Yang,Gaofeng Shu,Minjiang Chen,Hong Yuan,Jiansong Ji
CS-DHB NPs enabled pH-/laser-triggered DOX and HB codelivery for spatiotemporal HCC chemo-photothermal therapy. • Under 660 nm laser (1.0 W cm⁻²), NPs exhibited rapid hyperthermia, high ¹O₂ yield, and superior photostability. • In Hepa1-6 tumor models, NPs plus laser ensured 100% survival, marked tumor regression, and no notable toxicity. Hepatocellular carcinoma (HCC) remains lethal due to systemic chemotherapy is halted by cardiotoxicity, multidrug resistance, and poor tumor penetration. To address these limitations, we developed a novel modified chondroitin sulfate/cystamine nanoparticle, termed CS-DHB NPs, that co-delivers doxorubicin (DOX) and the photosensitizer hypocrellin B (HB) and is encapsulated within a chondroitin sulfate/cystamine nanocarrier. These engineered nanoparticles (∼154 nm) demonstrated high drug-loading efficiencies (DOX: 80%; HB: 60%), exceptional serum stability (>72 h), and dual-drug release in laser- and pH-dependent environments. Upon 660 nm laser irradiation (1.0 W cm⁻²), the CS-DHB NPs produced substantial photothermal, photodynamic effects (¹O₂ quantum yield: 0.56), and excellent photostability. The prepared CS-DHB NPs were biocompatible and showed efficient in vitro cytotoxic effects via CCK-8 assays and deep penetration and inhibition of multicellular tumor spheroids (MTS). Ex vivo cellular studies revealed that the targeted delivery mechanism, clathrin-dependent endocytosis, with laser-triggered uptake, enhanced intracellular DOX accumulation twofold. In Hepa1–6 cells, CS-DHB NPs treatment induced pronounced apoptosis (∼51%). In vivo, five intravenous administrations combined with localized laser irradiation resulted in significant tumor regression, 100% survival, minimal systemic toxicity, and no histopathological damage in a Hepa1–6-bearing C57BL/6 mice model. By integrating chemotherapy, phototherapy, and targeted release within a tumor-targeted nanosystem, CS-DHB NPs offer a promising strategy to overcome chemoresistance while preserving healthy tissues, advancing an effective, and clinically translatable approach for synergistic HCC therapy.
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Advanced Healthcare Materials
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2026
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IF 11
Yunan Yuan,Yijun Wu,Jiaxuan Yang,Fujiang Li,Ruonan Huang,Qian Cheng,Yan Rong,Chaoliang He
The therapeutic efficacy of melanoma immunochemotherapy is severely limited by insufficient intratumoral drug retention, systemic toxicity, and immunosuppressive tumor microenvironment (TME). Thus, we developed a single-dose injectable localized chemo-immunotherapy platform that enables sustained tumor-restricted delivery and synergistic immune remodeling. This hybrid system integrates doxorubicin-loaded tumor-derived exosome-coated hollow mesoporous silica nanoparticles (DeH) with a mannose-modified β-cyclodextrin-polyethyleneimine carrier co-delivering dual Toll-like receptor agonists (RC-MCP) within a thermoresponsive polypeptide hydrogel (mPEG- b -PELG). The biomimetic exosome coating provides an exosome-sheathed nanostructure and amplifies doxorubicin-induced immunogenic cell death. Mannose-mediated targeting facilitates preferential uptake by antigen-presenting cells and enhances endosomal Toll-like receptor signaling, leading to robust dendritic cell maturation. Following intratumoral injection, the hydrogel undergoes in situ sol-gel transition to form a stable drug depot, enabling sustained and coordinated release while minimizing systemic exposure. As a result, a single intratumoral administration elicits potent antitumor immune responses, significantly suppresses tumor growth, alleviates TME immunosuppression, and exhibits favorable biocompatibility in murine melanoma model. Collectively, this work presents a rationally designed single-dose localized chemo-immunotherapy strategy for melanoma treatment.
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SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
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2026
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IF 4.8
Jin-Xian Luo,Qing Fan,Qing Tang,Zhu Tao,Ying Huang
A supramolecular gel was constructed based on chitosan (CS) and cucurbit[5]uril (Q[5]) through self-assembly via hydrogen bonds and ion-dipole interactions. This gel possesses a dense three-dimensional network structure that provides a rigid microenvironment for encapsulating 6-bromo-2-methylquinoline (6-Br-2-MQ), successfully inducing room-temperature phosphorescence (RTP) emission at 511 nm with a phosphorescence lifetime of 1.537 ms and a quantum yield of 6.72%. Mechanistic studies indicate that the RTP emission originates from the synergistic effects of the rigid gel matrix, host-guest interactions at the Q[5], and the bromine-induced heavy-atom effect. The RTP system exhibits reversible temperature-responsive “on-off” behavior. Furthermore, based on a resonance energy transfer mechanism, the system serves as a phosphorescence probe for the detection of doxorubicin (DOX) in complex biological matrices with a detection limit of 0.65 μM, utilizing a PRET-based dynamic quenching mechanism. The probe shows good recovery (96.08–100.75%) and high anti-interference capability in artificial urine samples. This study provides a new strategy for developing RTP materials using naturally derived and biocompatible components, and demonstrates their potential as a simple, cost-effective platform for point-of-care biosensing applications in complex biological fluids.
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Frontiers in Bioengineering and Biotechnology
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2025
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IF 4.8
Qiang Zhang,Yu Zhang,Hui Chen,Lei-Na Sun,Bin Zhang,Dong-Sheng Yue,Chang-Li Wang,Zhen-Fa Zhang
Introduction: Elderly osteosarcoma patients often face significant postoperative challenges, including high recurrence rates and delayed wound healing. These issues are primarily due to inadequate hemostasis, reactive oxygen species (ROS)-mediated microenvironmental inhibition, and compromised bone regeneration. This study aims to address these challenges by introducing a multifunctional adhesive hydrogel designed for synergistic therapy.Methods: The hydrogel consists of carboxymethyl chitosan methacryloyl (CMCSMA) and tannic acid (TA), which form a dynamic, crosslinked polymer network capable of rapid tissue adhesion and adaptability to moist wound environments. The hydrogel incorporates ginger vesicles (GVs) loaded with doxorubicin (DOX), offering a dual therapeutic approach. The system facilitates hemostasis through physical barrier formation and activation of coagulation factors, while GVs and DOX provide controlled release for ROS scavenging, reduction of inflammation, and targeted tumor cell elimination.Results: In vitro experiments demonstrated the hydrogel’s ability to efficiently remove ROS and promote osteogenic differentiation. In a rat osteosarcoma resection model, the hydrogel significantly shortened hemostasis time compared to conventional sponges, reduced tumor recurrence, and accelerated wound healing.Discussion: This study presents a multifunctional hydrogel that combines hemostasis, antioxidation, tissue repair, and recurrence prevention. The findings suggest that this integrated therapeutic approach holds substantial potential for clinical application in elderly osteosarcoma treatment, addressing critical postoperative challenges and improving patient outcomes.
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RSC Advances
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2025
·Vol. 15
·期 46
·38585-38596
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IF 4.6
Shukai Sun,Yue Zhai,Qingwu Tian,Peng Zhao,Hong Cheng,Deng Pan,Junna Sui,Yusun Zhou,Chao Xuan,Tingting Zhou
Magnetic molecularly imprinted polymers (MMIPs) were synthesized using magnetic Fe3O4@SiO2 as a carrier for the selective recognition and adsorption of doxorubicin (DOX) and epirubicin (EPI) in plasma. Then, the method was combined with high-performance liquid chromatography-ultraviolet detection (HPLC-UV) to realize rapid and accurate detection of DOX and EPI concentrations in plasma. The structures of the prepared MMIPs were characterized by X-ray diffraction, transmission electron microscopy, X-ray photoelectron spectroscopy, and magnetic saturation. As observed, the prepared MMIPs had a uniform appearance and excellent magnetic properties. Then, the adsorption performance of MMIPs was verified through static, dynamic, and selective adsorption tests. MMIPs were found to have high adsorption capacity (8.36 and 8.19 mg g−1), high selectivity (imprinting factors of 34.83 and 8.03), and rapid adsorption for DOX and EPI, respectively. Next, HPLC-UV was used for quantitative analysis. The prepared method had a good linear relationship (0.0001–0.5 mg mL−1 for DOX and 0.0002–0.5 mg mL−1 for EPI) and low detection limits (0.04613 ng mL−1 for DOX and 0.08969 ng mL−1 for EPI). The combination of magnetic solid-phase extraction and HPLC-UV was a highly specific and sensitive method for determining DOX and EPI concentrations in plasma.
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Biomaterials Science
·
2026
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IF 6.1
Min Zhang,Chunmiao Chen,Dandan Sun,Dayan Yang,Lingling Qin,Yanhua Cui,Xiangxiang Jing
Although the co-delivery of chemotherapeutic agents and sonosensitizer has been studied for years, developing an efficiency co-delivery nanocarrier that combine chemotherapy and sonodynamic therapy (SDT) with precise targeting remains a challenge. In this study, we prepared a folic acid (FA)-functionalized poly (lactic-coglycolic acid) (PLGA) nanoparticle (FPMD NP) that co-loaded with doxorubicin (Dox) and the sonosensitizer manganese (III) meso-tetrakis(4-carboxyphenyl) porphyrin (MnTPP) via a double-emulsion solvent evaporation method. Upon ultrasound irradiation, oxidative stress and apoptotic signaling were activated, which revealed by transcriptomic analysis. In vivo, the combination of FPMD NPs with ultrasound achieved tumor targeting, and tumor growth suppression in BALB/c nude mice bearing HNE-1 xenografts. The body weight of BALB/c nude mice maintained stable and no histopathological abnormalities in major organs were detected. Overall, the FPMD NPs successfully integrate MnTPP-mediated SDT with Dox chemotherapy, and demonstrate strong antitumor efficacy and favorable biosafety, highlighting its potential for synergistic SDT and chemotherapy in nasopharyngeal carcinoma treatment.
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ACS Applied Materials & Interfaces
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2022
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IF 10.383
Qing Hu,Jiayi Yao,Xiaoqin Wang,Yanfang Wang,Xiaoling Fu,Ju Ma,Han Lin,Jiaqi Xu,Longhua Shen,Xiangbin Yu
Chemoimmunotherapy can synergistically enhance the therapeutic effects and decrease the side effects by a combined method. However, the effective targeted codelivery of various chemotherapeutic agents and siRNAs remains challenging. Although nanomedicine-based chemoimmunotherapy has shown great potential in cancer treatment in recent years, further effort is needed to simplify the nanocarrier designs and maintain their effective functions. Here, we report a simple but robust multifunctional liposomal nanocarrier that contains a pH-sensitive liposome (LP) shell and a dendritic core for tumor-targeted codelivery of programmed cell death ligand 1 (PD-L1) siRNA and doxorubicin (DOX) (siPD-L1@PM/DOX/LPs). siPD-L1@PM/DOX/LPs had a suitable particle size and zeta potential, excellent stability in serum, and pH-sensitive drug release in vitro. They exhibited significant cell proliferation inhibition compared to free DOX and DOX-loaded LPs and could escape endosomes, effectively release siRNA into the cytoplasm of MCF-7 cells, and significantly reduce the PD-L1 expression on tumor cells. In vivo imaging confirmed high accumulation of siPD-L1@PM/DOX/LPs at the tumor site. More importantly, compared with siPD-L1@PM/LPs or DOX alone, siPD-L1@PM/DOX/LPs were more effective in inhibiting tumor growth and activating cytotoxic T cells in vivo. In conclusion, this nanocarrier may hold promise as a codelivery nanoplatform to improve the treatment of various solid tumors.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2022
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IF 8.025
Panpan Song,Zhongxia Lu,Tianze Jiang,Wenwei Han,Xiangyan Chen,Xia Zhao
The complex tumor microenvironment (TME) makes it difficult for single chemotherapy to achieve satisfactory therapeutic effects. Here, chitosan-coated hyaluronic acid micelles (R/C/ [email protected] ) that co-delivers doxorubicin (DOX) and programmed death-ligand 1 small interfering RNA (siPD-L1) are developed to enhance anti-tumor effect by combination of immunotherapy and chemotherapy. The pH/reduction dual-responsive co-delivery micelles R/C/ [email protected] are spherical particles about 180 nm, and have good drug loading performance, stability, biocompatibility, and TME-responsive drug release properties. The CD44 receptor targeting HA significantly enhances the cellular uptake of DOX and siPD-L1, and siPD-L1 causes the immune infiltration of CD4 + /CD8 + T cells by silencing PD-L1 expression. In vivo studies show that R/C/ [email protected] exhibits significantly stronger anti-breast cancer effect than that of free DOX and micelles loaded only DOX. Therefore, the dual-stimulus responsive micelles provide a promising strategy for combining chemotherapy and siRNA-based immunotherapy to enhance efficacy.
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Frontiers in Cardiovascular Medicine
·
2022
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IF 5.846
Chen Cong,Liu Shuhong,Cao Gaozhen,Hu Yang,Wang Run,Wu Min,Liu Mingya,Yiu Kai Hang
Background: This study primarily explored the role of paeonol in doxorubicin (DOX)-induced chronic heart failure (CHF), considering the cardioprotective effect of paeonol on an epirubicin-induced cardiac injury.Methods: DOX-induced CHF-modeled rats were treated with paeonol. Cardiac function and myocardial damage in rats were evaluated by using the multifunction instrument, and the histopathology, apoptosis, and the expression of miR-21-5p and S-phase kinase-associated protein 2 (SKP2) in myocardium were detected. The target gene of miR-21-5p was confirmed by a dual-luciferase reporter assay. After the required transfection or paeonol treatment, the viability, apoptosis, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) of the DOX-induced cardiomyocytes were determined. Reverse-transcription quantitative-PCR (RT-qPCR) and Western blot were performed to quantify the expressions of miR-21-5p, SKP2, and apoptosis-related factors.Results: Paeonol improved cardiac function and also ameliorated the cardiac damage of CHF-modeled rats, where the downregulation of abnormally elevated myocardial damage markers, including brain natriuretic peptide, lactate dehydrogenase, renin, angiotensin II, aldosterone, and endothelin 1, was observed. Paeonol alleviated the histopathological injury and suppressed the apoptosis in CHF-modeled rats, inhibited miR-21-5p expression, and upregulated SKP2 expression in vitro and in vivo. miR-21-5p targeted SKP2. Paeonol and SKP2 increased the viability and MMP, but reduced apoptosis and ROS in the DOX-induced cardiomyocytes. miR-21-5p exerted effects opposite to PAE and SKP2, and it downregulated the expression of Bcl-2 and mitochondrion-Cytochrome c (Cyt c) and upregulated the expression of Bax, C-caspase-3, and cytoplasm-Cyt c. miR-21-5p reversed the effects of paeonol, and its effects were further reversed by SKP2.Conclusion: Paeonol shows a cardioprotective effect on DOX-induced CHF via regulating the miR-21-5p/SKP2 axis.- Paeonol inhibited miR-21-5p expression in doxorubicin-induced chronic heart failure rats and in doxorubicin-induced cardiomyocytes.- SKP2 was targeted by miR-21-5p and it was down-regulated in chronic heart failure rats and doxorubicin-induced cardiomyocytes.- Paeonol showed cardioprotective effects on doxorubicin-induced chronic heart failure via regulating miR-21-5p/SKP2/PI3K/AKT axis.
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International Journal of Nanomedicine
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2022
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IF 7.033
Ju Liang,Runfa Guo,Maosong Xuan,Qiankun Sun,Wenlan Wu
Purpose This study aimed to construct a DOX conjugate with liver tumor targeting and acid sensitivity based on a short aromatic peptide FFYEE, which could amplify the tumor inhibition efficacy of DOX and alleviate tissue toxicity. Methods A novel DOX-peptide conjugate, D-gal-FFYEE-hyd-DOX, was constructed by linking DOX to the side chain of FFYEE with acid-sensitive hydrazone bond and by modifying the C-terminal of peptide with α-D-galactosamine (D-gal) as targeting ligand. The structure of D-gal-FFYEE-hyd-DOX was characterized by mass spectrometry, infrared spectroscopy (IR), and UV-Vis spectroscopy (UV-Vis). The assembly characteristics of pentapeptide FFYEE and D-gal-FFYEE-hyd-DOX were observed by transmission electron microscope (TEM). In vitro drug release, cytotoxicity, endocytosis, in vivo antitumor experiment and histopathology analysis were investigated. Results Peptide FFYEE endowed the D-gal-FFYEE-hyd-DOX with self-assembly performance and improved biocompatibility. D-gal-FFYEE-hyd-DOX can self-assemble into nanofibers with a diameter of ~ 40 nm in neutral aqueous solution and significantly reduced the cytotoxicity of free DOX to L02 cells. In vitro drug release results showed that D-gal-FFYEE-hyd-DOX had acid sensitivity and controlled release characteristics. The cytotoxicity and endocytosis investigations confirmed that D-gal-FFYEE-hyd-DOX enhanced the cellular uptake of DOX and inhibition effect on HepG2 cells. In vivo antitumor experiment indicated that D-gal-FFYEE-hyd-DOX could significantly inhibit the growth of liver tumor in mice and reduce the side effects of DOX. Conclusion The conjugate D-gal-FFYEE-hyd-DOX with liver tumor targeting and acid sensitivity has the characteristics of strong tumor inhibition and low toxicity, hinting the great clinical application potential for targeted delivery of DOX in cancer treatment.
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MOLECULAR PHARMACEUTICS
·
2022
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IF 5.364
Nan Zhang,Jing Li,Wenxia Gao,Wangwei Zhu,Jianqin Yan,Ziyun He,Li Li,Fang Wu,Yuji Pu,Bin He
The combined delivery of chemotherapeutics with checkpoint inhibitors of the PD-1/PD-L1 pathway provides a new approach for cancer treatment. Small-molecule peptide inhibitors possess short production cycle, low immunogenicity, and fewer side effects; however, their potential in cancer therapy is hampered by the rapid biodegradation and a nanocarrier is needed for efficient drug delivery. Herein, anticancer drug doxorubicin (DOX) and PD-L1 inhibitor peptide P-12 are co-loaded by a lipid polymer nanocomplex based on poly(lactic-co-glycolic acid) (PLGA) and DSPE-PEG. Octaarginine (R8)-conjugated DSPE-PEG renders the LPN efficient internalization by cancer cells. The optimal nanomedicine LPN-30-R82K@DP shows a diameter of 125 nm and a DOX and P-12 loading content of 5.0 and 6.2%, respectively. LPN-30-R82K@DP exhibits good physiological stability and enhanced cellular uptake by cancer cells. It successfully induces immunogenic cell death and PD-L1 blockade in CT26 cancer cells. The in vivo antitumor study further suggests that co-loaded nanomedicine efficiently suppresses CT26 tumor growth and elicits antitumor immune response. This study manifests that lipid polymer nanocomplexes are promising drug carriers for the efficient chemo-immunotherapy of cancer.
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ACS Applied Materials & Interfaces
·
2022
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IF 10.383
Youqiang Fang,Zheng Liu,Haixia Wang,Xing Luo,Yanteng Xu,Hon Fai Chan,Shixian Lv,Yu Tao,Mingqiang Li
Tumor recurrence is a critical conundrum in the postoperative therapy, on account of severe bleeding with disseminated tumor cells, residual tumor cells, and the rich nutrient and oxygen supply transported to tumors by the abundant blood vessels. Biodegradable drug-loaded implants, inserted in the resection cavity right away upon the surgery, possess bleeding prevention and efficient chemotherapeutic capabilities, considered to be a promising strategy to efficiently inhibit the recurrence of the solid tumor. Here, we developed a sandwich-like composite consisting of the combretastatin A4 (CA4)-loaded 3D-printed scaffold and doxorubicin (DOX)-loaded electrospun fiber (Scaffold-CA4@Fiber-DOX), presenting hemostatic, chemotherapeutic, and antibacterial potencies. The lyophilized 3D-printed scaffold with a porous structure rapidly absorbed and clotted the blood cells and disseminated tumor cells to prevent bleeding and tumor metastasis. Subsequently, the preferentially released CA4 from the scaffold disrupted the microtubules of the vascular endothelial cell, resulting in vascular deformation and consequent insufficient nutrient supply to the solid tumor. The sustained release of DOX from the sandwiched electrospun fiber dramatically inhibited the peripheral tumor cell proliferation. This all-in-one multifunctional implant system, combining efficient vascular disruption and chemotherapy, provides a promising strategy for postoperative tumor therapy.
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