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.
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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生物医学工程
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免疫学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
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IF 10.5
Weiran Cao,Xue Zhang,Rui Li,Zijie Li,An Lu,Fei Yu,Lu Sun,Jiancheng Wang,Zhiyu Wang,Huining He
FOLFOX regimen, composed of folinic acid, 5-fluorouracil (5-FU) and oxaliplatin (OXP), has been used as clinical standard therapeutic regimen in treatments of colorectal cancer (CRC) and esophageal squamous cell carcinoma (ESCC). To further improve its therapeutic outcomes, FOLFOX was combined with anti-PD-1 antibody to form an advanced chemo-immune combination strategy, which has been proven more efficient in controlling cancer progression and prolonging patients' survival in various clinical trials. However, bad tumor accumulation, relative high toxicity, numerous treatment cycles with high fees and low compliance as well as drug resistance seriously limit the prognosis of FOLFOX regimen. The “all-in-one” formulations, which could precisely delivery multidrug regimen into tumor sites and cells, showed a promising application prospect for targeted drug delivery as well as reducing side effects. However, the design and preparation of the “all-in-one” formulation with high drug encapsulation efficiencies for all drugs was still challenging. Herein, a lipid core-shell nanoparticle codelivery platform was designed for simultaneous encapsulation of variant FOLFOX composed of miriplatin (MiPt), 5-Fluoro-2′-deoxyuridine 5′-monophosphate (FdUMP), calcium folinate ( CF ) and PD-L1 siRNA (siPD-L1) with high efficiencies, and their synergistic anti-tumor mechanisms were studied, respectively. MiPt, a precursor of OXP, was validated capable of inducing efficient immunogenic cell death (ICD) in this work. Additionally, ICD-mediated release of damage associated molecular patterns functionalized synergistically with PD-L1 silence by siPD-L1 to overcome chemoresistance, reverse suppressive tumor microenvironment and recruit more CD8 + T cells. FdUMP, as the intracellular active form of 5-FU, could induce large amounts of reactive oxygen species to enhance the ICD. CF worked as the sensitizer of FdUMP. The enhanced long-term anti-tumor effect of the prepared “all-in-one” formulation compared to free drug regimen and other controls, was verified in heterotopic CRC mice models and ESCC mice models, providing new thoughts for researchers and showing a promising prospect of translation into clinical applications.
研究领域:
纳米技术
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癌症研究
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药学
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免疫疗法
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Mengyue Li,Hanxi Zhang,Peizheng Xiong,Yuhan He,Wanyi Zhou,Chunhui Wu,Xiaoling Liao,Wei Zhang,Hong Yang,Yiyao Liu
Developing effective nanoplatforms for chemo-immunotherapy to achieve enhanced tumor suppression and systemic antitumor immunity has recently received extensive attention. Herein, we formulated a multifunctional DNA sandwich nanodevice, DSWAC/siPD-L1, based on triangular DNA origami, to implement enhanced cancer chemo-immunotherapy. Taking advantage of the tumor-targeting ability of the AS1411 aptamer, DSWAC/siPD-L1 efficiently delivered doxorubicin (DOX), CpG, and siPD-L1 into tumor cells. Moreover, the sandwich cavity spatially protects siPD-L1 from degradation, and the featured design of the DNA/RNA duplex linkers ensures effective intracellular release of siPD-L1. The pH-responsive release of cytotoxic DOX induces apoptosis and initial mild immunogenic cell death of tumor cells, presenting antigens to enhance the maturation of dendritic cells (DCs) with the assistance of the immune adjuvant CpG, thereby activating cytotoxic T lymphocytes to amplify antitumor immunity. Simultaneously, siPD-L1 downregulated the endogenous expression of PD-L1 to inhibit adaptive tumor immune escape. DSWAC/siPD-L1 initiated the iterative revolution of the cancer-immunity cycle, leading to the inhibition of primary and metastatic tumors, as demonstrated by DC maturation and T-cell infiltration in established subcutaneous primary tumor model and metastatic lung tumor model. Furthermore, the superior antitumor effect of DSWAC/siPD-L1 resulted in approximately 91 % inhibition of primary tumor growth and 93 % prevention of lung metastasis. Collectively, this study describes a siPD-L1-based sandwich DNA nanodevice functionalized with AS1411/CpG for enhanced cancer chemo-immunotherapy, inspiring the creation of more innovative drug nanocarriers and the exploitation of novel cancer therapies.
研究领域:
纳米医学
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肿瘤学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
INORGANIC CHEMISTRY COMMUNICATIONS
·
2026
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IF 5.4
Meijuan Shi,Huirui Zhu,Yijie Wang,Yumeng Guo,Yuyao Wang,Hongqin Wang,Na Wang,Tao Gong,Rui Guo
Graphene oxide (GO) nanostructures enable precision tumor delivery of anticancer drugs/genes, enhancing bioavailability and supporting photothermal tumor ablation. However, existing research predominantly focuses on single tumor-targeting strategies, there is still an urgent need to explore GO-based nanodelivery platforms with broad-spectrum antitumor effects. This study presents a facile and green synthesis method to prepare GO nanostructure (GO-PEG-PEI-FA, GPPF) for targeted delivery of si PD-L1 and photothermal-immunotherapy for cancer treatment. GPPF can be selectively internalized by MDA-MB-231 , HCT116 , and A2780 cells, subsequently achieving lysosomal escape and downregulating PD-L1 gene expression by approximately 69%. Under 808 nm laser irradiation, 40 μg/ml GPPF reduced the viability of three cancer cell lines by 22.91%, 27.31%, and 60.06%, respectively. The photothermal effect induced elevated ROS generation, promoting immunogenic cell death in tumor cells. Either GPPF/si PD-L1 alone or in combination with phototherapy significantly inhibited the growth of triple-negative breast cancer tumors, with synergistic enhancement of cytotoxic T lymphocytes infiltration. This study provides insights into the design of GO-based platforms to combine photothermal therapy and immunotherapy, particularly for triple-negative breast cancer.
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产品关联
DOI
高影响因子
Advanced Science
·
2022
·Vol. 9
·期 15
·2105894
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IF 17.521
Pengkai Wu,Haitian Zhang,Yin Yin,Meiling Sun,Shuai Mao,Huihui Chen,Yexuan Deng,Shuai Chen,Shuo Li,Beicheng Sun
Nano-based immunotherapy of therapeutic biomolecules is attractive but tremendously hampered by the poor delivery efficiency. This study reports a novel delivery system of fluorinated-coordinative-epigallocatechin gallate (EGCG), referring as FEGCG/Zn, through the integration of fluorination and zinc ions (Zn 2+ ) into EGCG. The robust therapeutics of FEGCG/Zn are measured in terms of the regulating effect on programmed cell death ligand 1 (PD-L1), the effective delivery of diverse biomolecules, and the hitchhiking ability using living cells. Taking small interfering RNA of PD-L1 (siPD-L1) and erythrocytes as an example, the fabricated biomimetic system achieves excellent siPD-L1 delivery and further improves siPD-L1 accumulation in tumors. Finally, the combination of FEGCG/Zn and siPD-L1 promotes antitumor immunotherapy through alleviation of T cells exhaustion by regulating PD-L1 expression in tumor cells. The results demonstrate that FEGCG/Zn substantially regulates PD-L1 expression and improves immune-biomolecule delivery by forming biomimetic nanoassemblies, offering a versatile platform for cancer immunotherapy.
研究领域:
纳米技术
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癌症研究
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免疫学
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药物递送系统
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCONJUGATE CHEMISTRY
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2026
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IF 4.5
Kui Xiong,Lili Xia,Lin Zhang,Weiyuan Li,Yan An,Xiangyang Shi,Guang-Zhi Jin
Abstract Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma and remains challenging to treat at advanced stages due to immune evasion and inefficient intracellular delivery of therapeutic agents. In this study, we synthesized a modified generation 5 (G5) poly(amidoamine) dendrimer (G5PBA) to co-deliver small-interfering RNA targeting programmed death-ligand 1 (siPD-L1) and the antitumor peptide Tat-HSPB1, forming the G5PBA/siPD-L1/Tat-HSPB1 nanocomplex. The agarose gel retardation assay demonstrated that G5PBA efficiently condensed siPD-L1. Furthermore, the peptide encapsulation efficiency and loading capacity were measured, confirming the loading of Tat-HSPB1 into G5PBA/siPD-L1. Flow cytometry showed that G5PBA enhanced the cellular uptake of siPD-L1, while confocal microscopy demonstrated that G5PBA promoted lysosomal escape in Caki-1 cells. Western blot analysis further confirmed that G5PBA effectively reduced the PD-L1 protein expression. In cellular experiments, CCK-8, EdU, and wound-healing assays demonstrated that G5PBA/siPD-L1/Tat-HSPB1 inhibited the viability and migration of ccRCC cells. G5PBA/siPD-L1/Tat-HSPB1 suppressed tumor growth, downregulated PD-L1 expression, enhanced CD4+ and CD8+ T-cell infiltration, and elevated serum levels of IL-2, IL-6, TNF-α, and IFN-γ in mice. Major organs exhibited no obvious histopathological abnormalities upon H&E staining. Serum ALT, AST, and BUN levels showed no significant changes compared with the PBS group, suggesting the preliminary safety profile of G5PBA/siPD-L1/Tat-HSPB1. Collectively, the nanocomplex achieved efficient peptide/siPD-L1 co-delivery and demonstrated significant antitumor activity. This system thus provides a promising strategy and experimental basis for local administration of ccRCC.
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DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
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IF 13.3
Tong Li,Dianwei Wang,Meng Meng,Xiaoya Guo,Lin Lin,Zhiyu Yang,Zhen Li,Longwei Xiang,Cong Liu,Jie Chen,Xuan Pang,Kai Hao,Huayu Tian,Xuesi Chen
Numerous studies have established the promise of combining phototherapy and gene therapy. However, there are persistent obstacles hindering the full optimization of this combined therapeutic approach, such as the maximum development of photosensitizers and the construction of high-performance gene carriers. The LEGO stacking characteristics of COFs have brought infinite imagination to the construction of delivery systems, allowing for the design of responsive nano castles based on different application scenarios. Here, we have constructed a novel cationic multifunctional nano COF nucleic acid delivery system based on photosensitizer and cationic monomers. The long-range ordered structure of COF effectively regulates the spatial distribution of photosensitizer, thereby preserving their phototherapy efficacy. Simultaneously, the inherent cationic porous nanostructure equips COF with exceptional capabilities for delivering nucleic acids. This integrated multifunctional nano delivery system significantly enhances the combined efficacy of phototherapy and gene therapy. The phototherapy capacity of COF enables precise tumor elimination in a spatiotemporal manner, inducing robust ICD and activating immune cells at the tumor site. Furthermore, loaded siPD-L1 significantly enhances immune cell recognition and killing of tumor cells, effectively shielding mice from re-invasion and tumor metastasis. The development of multifunctional nanomedicine based on COF provides new ideas for efficient tumor combination therapy.
研究领域:
纳米医学
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治疗学
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分子生物学
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癌症研究
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材料科学
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产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Yu Tian,Hongshu Jing,Quan Wang,Suxian Hu,Zhihua Wu,Yourong Duan
Immune checkpoint blockade, especially the programmed cell death ligand 1 (PD-L1) blockade, has revolutionized the treatment of melanoma . However, PD-1/PD-L1 monotherapy leads to unsatisfactory therapeutic outcomes. The immunotherapy of melanoma could be improved by adding doxorubicin (DOX), which triggers immunogenic cell death (ICD) effect to activate anti-tumor immunity. Additionally, microneedles, especially dissolving microneedles (dMNs), can further enhance outcomes of chemo-immunotherapy due to the physical adjuvant effect of dMNs. Herein, we developed the dMNs-based programmed delivery system that incorporated pH-sensitive and melanoma-targeting liposomes to co-deliver DOX and siPD-L1, achieving enhanced chemo-immunotherapy of melanoma (si/ [email protected] dMNs). The incorporated si/ [email protected] LPs demonstrated uniform particle size, pH-sensitive drug release, high in vitro cytotoxicity and targeting ability. Besides, si/ [email protected] LPs effectively downregulated the expression of PD-L1, induced tumor cell apoptosis and triggered ICD effect. The si/ [email protected] LPs also showed deep penetration (approximately 80 μm) in 3D tumor spheroids. Moreover, si/ [email protected] dMNs dissolved rapidly into the skin and had sufficient mechanical strength to penetrate skin, reaching a depth of approximately 260 μm in mice skin. In mice model of melanoma tumor, si/ [email protected] dMNs exhibited better anti-tumor efficacy than monotherapy by dMNs and tail intravenous injection at the same dose. This was due to the higher cytotoxic CD8 + T cells and the secreted cytotoxic cytokine IFN-γ evoked by si/ [email protected] dMNs, thereby eliciting strong T-cell mediated immune response and resulted in enhanced anti-tumor effects. In conclusion, these findings suggested that si/ [email protected] dMNs provided a promising and effective strategy for enhanced chemo-immunotherapy of melanoma.
研究领域:
肿瘤学
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药学
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免疫学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Matter
·
2022
·
IF 19.967
Yunfei Yi,Mian Yu,Chan Feng,Huisong Hao,Weiwei Zeng,Chuchu Lin,Hongzhong Chen,Feng Lv,Dunwan Zhu,Xiaoyuan Ji,Lin Mei,Meiying Wu,Wei Tao
Summary It is highly desirable to turn “cold” tumors into “hot” ones to improve the efficacy of antitumor immunotherapy. Herein, we develop the peptide-based small interfering RNA (siRNA) micelleplexes (P A7R @siPD-L1) for normalizing vascular-immune crosstalk to establish a positive feedback loop in potentiating antitumor immunotherapy. These micelleplexes are equipped with tumor-microenvironment-responsive property for precise drug delivery and release. The prepared P A7R @siPD-L1-mediated photodynamic therapy could eliminate solid tumors and trigger immunogenic cell death to generate systematic immune responses. Meanwhile, the antiangiogenic peptide A7R normalizes the tumor vasculature by converting chaotic vascular systems into matured and organized ones, thus alleviating tumor hypoxia and promoting intratumoral infiltration by immune cells. Antitumor immunogenicity would be further strengthened with the aid of siPD-L1 by muting the resistance of tumor cells against immune effector cells. This study provides a unique therapeutic strategy in turning “cold” tumors into “hot” tumors enabled by siRNA nanomaterial .
研究领域:
肿瘤学
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免疫疗法
·
纳米医学
·
癌症生物学
✓ 已验证
DOI
高影响因子
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