International Journal of Nanomedicine
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2018
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IF 4.37
Zhen Zhang,Hanqing Qian,Jie Huang,Huizi Sha,Hang Zhang,Lixia Yu,Baorui Liu,Dong Hua,Xiaoping Qian
Background Red blood cell membrane-coated nanoparticle (RBCm-NP) platform, which consist of natural RBCm and synthetic polymeric core, can extend circulation time in vivo with an improved biocompatibility and stability of this biomimetic nanocarrier. To achieve better bioavailability of antitumor drugs that were loaded in RBCm-NPs, the functionalization of coated RBCm with specific targeting ability is essential. Bispecific recombinant protein anti-EGFR-iRGD, containing both tumor penetrating peptide (internalizing RGD peptide) and EGFR single-domain antibody (sdAb), seems to be an optimal targeting ligand for RBCm-NPs in the treatment of multiple tumors, especially colorectal cancer with high EGFR expression. Materials and methods We modified the anti-EGFR-iRGD recombinant protein on the surface of RBCm-NPs by lipid insertion method to construct iE–RBCm–PLGA NPs and confirmed the presentation of active tumor-targeting ability in colorectal cancer models with high EGFR expression when compared with RBCm–PLGA NPs. In addition, potential anti-tumor drug gambogic acid (GA) was loaded into the NPs to endow the antitumor efficiency of iE–RBCm–GA/PLGA NPs. It was simultaneously evaluated whether GA can reach better biocompatibility benefiting from the improved antitumor efficiency of iE–RBCm–GA/PLGA NPs in colorectal cancer models. Results We successfully modified anti-EGFR-iRGD proteins on the surface of biomimetic NPs with integrated and stable “shell–core” structure. iE–RBCm–PLGA NPs showed its improved targeting ability in vitro (multicellular spheroids [MCS]) and in vivo (nude mice bearing tumors). Besides, no matter on short-term cell apoptosis at tumor site (terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling [TUNEL]) and long-term tumor inhibition, iE–RBCm–GA/PLGA NPs achieved better antitumor efficacy than free GA in spite of the similar effects of cytotoxicity and apoptosis to GA in vitro. Conclusion We expect that the bispecific biomimetic nanocarrier can extend the clinical application of many other potential antitumor drugs similar to GA and become a novel drug carrier in the colorectal cancer treatment.
研究领域:
纳米技术
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药学
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肿瘤学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Chemistry
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2026
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IF 7.4
Shuoye Yang,Jinpeng Wang,Qianqian Cheng,Huajian Yuan,Lin Ju,Xin Wang,Suxi Liu,Ruolan Song,Ning Li,Lu Zhang,Peng Li
Chemotherapy drugs are often associated with toxic side effects and low bioavailability, while solid tumors like breast cancer frequently exhibit multidrug resistance, which limits the clinical efficacy of chemotherapy and other monotherapies. To address these challenges, there is a need for the development of efficient delivery systems capable of transporting various therapeutic agents while introducing novel programmed death mechanisms to achieve synergistic antitumor effects. In this study, zeolite imidazole-8 (ZIF-8) was utilized as a core carrier to load doxorubicin (DOX) and photothermal agent CuS, and further coated by folic acid (FA)-functionalized red blood cell membranes (RBCM) to fabricate the FRCZD delivery system. This system possessed the capacity to target breast cancer MCF-7 cells and their drug-resistant strain, MCF-7/ADR cells. Notably, DOX and CuS were rapidly released in response to both the tumor microenvironment (TME) and near-infrared radiation (NIR). Under light stimulation, CuS induced photothermal therapy (PTT), which further enhanced localized drug accumulation while catalyzing H 2 O 2 to produce toxic hydroxyl radicals (⋅OH) that triggered chemodynamic therapy (CDT). Moreover, excessive intake of Cu 2+ led to mitochondrial metabolic dysfunctions that ultimately initiated cuproptosis. The results demonstrated that FRCZD combined with NIR accelerated cell apoptosis while interfering with cell cycle distribution, consequently inhibiting tumor cell proliferation and migration. In vivo experiment results further corroborated that FRCZD + NIR significantly inhibited tumor growth more effectively than other experimental groups while exhibiting favorable biological safety profiles. Overall, the integrated platform FRCZD could substantially enhance treatment outcomes by inducing cuproptosis in conjunction with chemotherapy, PTT, and CDT approaches, thus holding promise for advancing therapies against drug-resistant tumors.
✓ 已验证
产品关联
DOI
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2020
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IF 4.545
Song Chen,Yujie Ren,Peng Duan
Lung cancer still remains a leading cause of cancer mortality in the world. Obatoclax mesylate (OM), a B cell chronic lymphocytic leukemia/lymphoma 2 (Bcl-2) family antagonist, is a potential antitumor drug. However, its poor aqueous solubility restricts its clinical application. Although these inherent defects, nanotechnology can be used to improve the solubility and tumor target of OM, promoting its antitumor efficiency. In the present study, the poly(lactic-coglycolic acid) (PLGA) was used and combined with red blood-cell membrane (RBCm) to explore if OM-loaded RBCm nanoparticles could improve the antitumor efficacy of OM for the treatment of lung cancer with relatively lower side effects compared with the free OM. The good physicochemical stability of the prepared RBCm-OM/PLGA nanoparticles was confirmed, and the optimal size of 153 nm was screened out, along with sustained drug release behavior. We found that RBCm-OM/PLGA nanoparticles effectively reduced the proliferation of lung cancer cells. Additionally, RBCm-OM/PLGA nanoparticles considerably induced apoptosis in lung cancer cells by reducing Bcl-2 expression levels, accompanied with the improved Cyto-c releases in cytoplasm and Caspase-3 activation. Mitochondrial membrane potential was also obviously impaired in lung cancer cells incubated with RBCm-OM/PLGA nanoparticles. Compared with free OM, RBCm-OM/PLGA nanoparticles could greatly prolong the drug circulation time in vivo and upgraded the drug concentration accumulated in tumor tissue. Furthermore, RBCm-OM/PLGA nanoparticles exerted stronger antitumor efficacy in vivo against lung cancer progression with superior safety. Therefore, RBCm-OM/PLGA nanoparticles provided new potential for lung cancer therapy with the improved safety and therapeutic effect.
研究领域:
药理学
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肿瘤学
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纳米技术
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生物医学工程
✓ 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）