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Synchronous targeted delivery of TGF- β siRNA to stromal and tumor cells elicits robust antitumor immunity against triple-negative breast cancer by comprehensively remodeling the tumor microenvironment
Biomaterials. 2023 Jul 25;301:122253. doi: 10.1016/j.biomaterials.2023.122253. Online ahead of print.ABSTRACTThe poor permeability of therapeutic drugs, limited T-cell infiltration, and strong immunosuppressive tumor microenvironment of triple-negative breast cancer (TNBC) acts as a prominent barrier to the delivery of drugs and immunotherapy including programmed cell death ligand-1 antibody (anti-PD-L1). Transforming growth factor (TGF)-β, an important cytokine produced by cancer-associated fibroblasts (CAFs) and tumor cells contributes to the pathological vasculature, dense tumor stroma and strong immunosuppressive tumo...
Source: Biomaterials - August 3, 2023 Category: Materials Science Authors: Mengmeng Yang Chao Qin Linlin Tao Gang Cheng Jingjing Li Fangnan Lv Nan Yang Zuhang Xing Xinyu Chu Xiaopeng Han Meirong Huo Lifang Yin Source Type: research

The programmed site-specific delivery of LY3200882 and PD-L1 siRNA boosts immunotherapy for triple-negative breast cancer by remodeling tumor microenvironment
In this study, we successfully constructed a programmed site-specific delivery nanosystem for the combined delivery of transforming growth factor beta (TGF-β) receptor inhibitor LY3200882 (LY) and PD-L1 siRNA (siPD-L1) to boost anti-tumor immunotherapy. As expected, LY in the outer layer of the nanosystem was released by stimulation of MMP2, and dramatically down-regulated the expression of extracellular matrix (ECM) in the tumor-associated fibroblasts (TAFs), and thus promoted the infiltration of effector T cells and penetration of nanomedicines. Simultaneously, the blockade of TGF-β by LY also triggered immunogenic cel...
Source: Biomaterials - April 24, 2022 Category: Materials Science Authors: Pan Zhang Chao Qin Nan Liu Xinyuan Zhou Xuxin Chu Fangnan Lv Yongwei Gu Lifang Yin Jiyong Liu Jianping Zhou Meirong Huo Source Type: research

Asynchronous blockade of PD-L1 and CD155 by polymeric nanoparticles inhibits triple-negative breast cancer progression and metastasis
Biomaterials. 2021 Jun 24;275:120988. doi: 10.1016/j.biomaterials.2021.120988. Online ahead of print.ABSTRACTPD-L1/PD-1 blockade therapy shows durable responses to triple-negative breast cancer (TNBC), but the response rate is low. CD155 promotes tumor metastasis intrinsically and modulates the immune response extrinsically as the ligand of DNAM-1 (costimulatory receptor) and TIGIT/CD96 (coinhibitory receptors). Herein, we verified that TNBC cells coexpressed PD-L1 and CD155. By examining the receptors of PD-L1 and CD155 on TNBC tumor-infiltrating lymphocytes (TILs) over time, we observed that PD-1 and DNAM-1 were upregula...
Source: Biomaterials - June 29, 2021 Category: Materials Science Authors: Chuanrong Chen Qianqian Guo Hao Fu Jian Yu Liting Wang Ying Sun Jiali Zhang Yourong Duan Source Type: research

Delivery of small interfering RNA against Nogo-B receptor via tumor-acidity responsive nanoparticles for tumor vessel normalization and metastasis suppression.
This study demonstrated that NgBR is a promising therapeutic target in abnormal tumor vasculature and aggressive cancer cells, and the tumor-responsive nanoparticle with the feature of charge transformation offers great potential for tumor-specific delivery of gene therapeutics. PMID: 29803999 [PubMed - as supplied by publisher]
Source: Biomaterials - May 21, 2018 Category: Materials Science Authors: Wang B, Ding Y, Zhao X, Han X, Yang N, Zhang Y, Zhao Y, Zhao X, Taleb M, Miao QR, Nie G Tags: Biomaterials Source Type: research

Ultrasound assisted gene and photodynamic synergistic therapy with multifunctional FOXA1-siRNA loaded porphyrin microbubbles for enhancing therapeutic efficacy for breast cancer.
Abstract To improve the non-invasive therapeutic efficacy for ER positive breast cancer (ER+ BC), we fabricated a multifunctional FOXA1 loaded porphyrin microbubble to combine photodynamic therapy (PDT) and gene therapy of FOXA1 knockdown (KD) with ultrasound targeted microbubble destruction (UTMD) technology under the guidance of contrast enhanced ultrasound (CEUS). Cationic porphyrin microbubbles (CpMBs) were firstly fabricated from a porphyrin grafted lipid with two cationic amino groups (PGL-NH2) and fluorocarbon inert gas of C3F8. Porphyrin group in the CpMBs monolayer could be used as a photosensitizer for ...
Source: Biomaterials - May 3, 2018 Category: Materials Science Authors: Zhao R, Liang X, Zhao B, Chen M, Liu R, Sun S, Yue X, Wang S Tags: Biomaterials Source Type: research

Polymeric nanoparticles of siRNA prepared by a double-emulsion solvent-diffusion technique: Physicochemical properties, toxicity, biodistribution and efficacy in a mammary carcinoma mice model.
Abstract siRNA-loaded nanoparticles (NPs) administered systemically can overcome the poor stability and rapid elimination of free double-stranded RNA in circulation, resulting in increased tumor accumulation and efficacy. siRNA against osteopontin (siOPN), a protein involved in breast cancer development, was encapsulated in poly(D,L-lactic-co-glycolic acid) NPs by a double emulsion solvent diffusion (DESD) technique. We also compared the effect of polyethylenimine (PEI) molecular weight (800 Da and 25 kDa), used as the counter-ion for siRNA complexation, on the physicochemical properties of the NPs, cytotoxicity...
Source: Biomaterials - August 23, 2017 Category: Materials Science Authors: Ben David-Naim M, Grad E, Aizik G, Nordling-David MM, Moshel O, Granot Z, Golomb G Tags: Biomaterials Source Type: research

Inhibition of metastasis and growth of breast cancer by pH-sensitive poly (β-amino ester) nanoparticles co-delivering two siRNA and paclitaxel.
Abstract Breast cancer is the most vicious killer for women's health, while metastasis is the main culprit, which leads to failure of treatment by increasing relapse rate. In this work, a new complexes nanoparticles loading two siRNA (Snail siRNA (siSna) and Twist siRNA (siTwi)) and paclitaxel (PTX) were designed and constructed using two new amphiphilic polymer, polyethyleneimine-block-poly[(1,4-butanediol)-diacrylate-β-5-hydroxyamylamine] (PEI-PDHA) and polyethylene glycol-block-poly[(1,4-butanediol)-diacrylate-β-5-hydroxyamylamine] (PEG-PDHA) by self-assembly. The experimental results showed that in the 4T1 t...
Source: Biomaterials - February 25, 2015 Category: Materials Science Authors: Tang S, Yin Q, Su J, Sun H, Meng Q, Chen Y, Chen L, Huang Y, Gu W, Xu M, Yu H, Zhang Z, Li Y Tags: Biomaterials Source Type: research

Tuning PEGylation of mixed micelles to overcome intracellular and systemic siRNA delivery barriers.
Abstract A series of endosomolytic mixed micelles was synthesized from two diblock polymers, poly[ethylene glycol-b-(dimethylaminoethyl methacrylate-co-propylacrylic acid-co-butyl methacrylate)] (PEG-b-pDPB) and poly[dimethylaminoethyl methacrylate-b-(dimethylaminoethyl methacrylate-co-propylacrylic acid-co-butyl methacrylate)] (pD-b-pDPB), and used to determine the impact of both surface PEG density and PEG molecular weight on overcoming both intracellular and systemic siRNA delivery barriers. As expected, the percent PEG composition and PEG molecular weight in the corona had an inverse relationship with mixed mi...
Source: Biomaterials - December 6, 2014 Category: Materials Science Authors: Miteva M, Kirkbride KC, Kilchrist KV, Werfel TA, Li H, Nelson CE, Gupta MK, Giorgio TD, Duvall CL Tags: Biomaterials Source Type: research

Tumor targeting RGD conjugated bio-reducible polymer for VEGF siRNA expressing plasmid delivery.
Abstract Targeted delivery of therapeutic genes to the tumor site is critical for successful and safe cancer gene therapy. The arginine grafted bio-reducible poly (cystamine bisacrylamide-diaminohexane, CBA-DAH) polymer (ABP) conjugated poly (amido amine) (PAMAM), PAM-ABP (PA) was designed previously as an efficient gene delivery carrier. To achieve high efficacy in cancer selective delivery, we developed the tumor targeting bio-reducible polymer, PA-PEG1k-RGD, by conjugating cyclic RGDfC (RGD) peptides, which bind αvβ3/5 integrins, to the PAM-ABP using polyethylene glycol (PEG, 1 kDa) as a spacer. Physical cha...
Source: Biomaterials - May 31, 2014 Category: Materials Science Authors: Kim HA, Nam K, Kim SW Tags: Biomaterials Source Type: research

Direct cytosolic siRNA delivery by reconstituted high density lipoprotein for target-specific therapy of tumor angiogenesis.
We described here the mechanisms by which small interfering RNA (siRNA) molecules incorporated in reconstituted high density lipoprotein (rHDL) were efficiently transferred into the cytoplasm of cells to perform target-specific therapy of tumor angiogenesis. Using fluorescent-tagged apolipoprotein A-I (apoA-I) and cholesterol-conjugated siRNA (Chol-siRNA), it was confirmed with FACS and confocal microscopic measurements that Chol-siRNA-loaded rHDL nanoparticles (rHDL/Chol-siRNA complexes) were successfully established and apoA-I certainly was attached to the surface of Chol-siRNA-loaded lipoplexes (Lipos/Chol-siRNA complex...
Source: Biomaterials - May 27, 2014 Category: Materials Science Authors: Ding Y, Wang Y, Zhou J, Gu X, Wang W, Liu C, Bao X, Wang C, Li Y, Zhang Q Tags: Biomaterials Source Type: research

Polycation-functionalized nanoporous silicon particles for gene silencing on breast cancer cells.
Abstract Nanoporous silicon particles (pSi), with a pore size in the range of 20-60 nm, were modified with polyethyleneimine (PEI) to yield pSi-PEI particles, which were subsequently complexed with siRNA. Thus, pSi-PEI/siRNA particles were fabricated, with the PEI/siRNA nanocomplexes mainly anchored inside the nanopore of the pSi particles. These hybrid particles were used as carriers to deliver siRNA to human breast cancer cells. Due to the gradual degradation of the pSi matrix under physiological conditions, the PEI/siRNA nanocomplexes were released from the pore interior in a sustained manner. Physicochemical ...
Source: Biomaterials - October 5, 2013 Category: Materials Science Authors: Zhang M, Xu R, Xia X, Yang Y, Gu J, Qin G, Liu X, Ferrari M, Shen H Tags: Biomaterials Source Type: research

Acid-degradable core-shell nanoparticles for reversed tamoxifen-resistance in breast cancer by silencing manganese superoxide dismutase (MnSOD).
This study attempted to reverse tamoxifen (TAM)-resistance in breast cancer by silencing a mitochondrial enzyme, manganese superoxide dismutase (MnSOD), which dismutates TAM-induced reactive oxygen species (ROS) (i.e., superoxide) to less harmful hydrogen peroxide and hampers therapeutic effects. Breast cancer cells were co-treated with TAM and MnSOD siRNA-delivering nanoparticles (NPs) made of a siRNA/poly(amidoamine) (PAMAM) dendriplex core and an acid-degradable polyketal (PK) shell. The (siRNA/PAMAM)-PK NPs were designed for the PK shell to shield siRNA from nucleases, minimize detrimental aggregation in serum, and fac...
Source: Biomaterials - September 19, 2013 Category: Materials Science Authors: Cho SK, Pedram A, Levin ER, Kwon YJ Tags: Biomaterials Source Type: research