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Humanized bispecific antibody (mPEG?×?HER2) rapidly confers PEGylated nanoparticles tumor specificity for multimodality imaging in breast cancer.

ABSTRACT: BACKGROUND:Developing a universal strategy to improve the specificity and sensitivity of PEGylated nanoaparticles (PEG-NPs) for assisting in the diagnosis of tumors is important in multimodality imaging. Here, we developed the anti-methoxypolyethylene glycol (mPEG) bispecific antibody (BsAb; mPEG?×?HER2), which has dual specificity for mPEG and human epidermal growth factor receptor 2 (HER2), with a diverse array of PEG-NPs to confer nanoparticles with HER2 specificity and stronger intensity. RESULT:We used a one-step formulation to rapidly modify the nanoprobes with mPEG?×?HER2 and optimized the modified ratio of BsAbs on several PEG-NPs (Lipo-DiR, SPIO, Qdot and AuNP). The ?HER2/PEG-NPs could specifically target MCF7/HER2 cells (HER2++) but not MCF7/neo1 cells (HER2+/-). The ?HER2/Lipo-DiR and ?HER2/SPIO could enhance the sensitivity of untargeted PEG-NPs on MCF7/HER2 (HER2++). In in vivo imaging, ?HER2/Lipo-DiR and ?HER2/SPIO increased the specific targeting and enhanced PEG-NPs accumulation at 175% and 187% on 24 h, respectively, in HER2-overexpressing tumors. CONCLUSION:mPEG?×?HER2, therefore, provided a simple one-step formulation to confer HER2-specific targeting and enhanced sensitivity and contrast intensity on HER2 positive tumors for multimodality imaging.

SUBMITTER: Cheng YA

PROVIDER: S-EPMC7457265 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Humanized bispecific antibody (mPEG × HER2) rapidly confers PEGylated nanoparticles tumor specificity for multimodality imaging in breast cancer.

Cheng Yi-An YA Wu Tung-Ho TH Wang Yun-Ming YM Cheng Tian-Lu TL Chen I-Ju IJ Lu Yun-Chi YC Chuang Kuo-Hsiang KH Wang Chih-Kuang CK Chen Chiao-Yun CY Lin Rui-An RA Chen Huei-Jen HJ Liao Tzu-Yi TY Liu En-Shuo ES Chen Fang-Ming FM

Journal of nanobiotechnology 20200827 1

<h4>Background</h4>Developing a universal strategy to improve the specificity and sensitivity of PEGylated nanoaparticles (PEG-NPs) for assisting in the diagnosis of tumors is important in multimodality imaging. Here, we developed the anti-methoxypolyethylene glycol (mPEG) bispecific antibody (BsAb; mPEG × HER2), which has dual specificity for mPEG and human epidermal growth factor receptor 2 (HER2), with a diverse array of PEG-NPs to confer nanoparticles with HER2 specificity and stronger inten ...[more]

PMID: 32854720

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Project description:Previous studies have shown that mithramycin A (MIT) is a promising candidate for the treatment of pancreatic carcinoma through inhibiting transcription factor Sp1. However, systemic toxicities may limit its clinical application. Here, we report a rationally designed formulation of MIT-loaded nanoparticles (MIT-NPs) with a small size and sustained release for improved passive targeting and enhanced therapeutic efficacy. Nearly spherical MIT-NPs with a mean particle size of 25.0±4.6 nm were prepared by encapsulating MIT into methoxy poly(ethylene glycol)-block-poly(d,l-lactic-co-glycolic acid) (mPEG-PLGA) nanoparticles (NPs) with drug loading of 2.11%±0.51%. The in vitro release of the MIT-NPs lasted for >48 h with a sustained-release pattern. The cytotoxicity of MIT-NPs to human pancreatic cancer BxPC-3 and MIA Paca-2 cells was comparable to that of free MIT. Determined by flow cytometry and confocal microscopy, the NPs internalized into the cells quickly and efficiently, reaching the peak level at 1-2 h. In vivo fluorescence imaging showed that the prepared NPs were gradually accumulated in BxPC-3 and MIA Paca-2 xenografts and retained for 168 h. The fluorescence intensity in both BxPC-3 and MIA Paca-2 tumors was much stronger than that of various tested organs. Therapeutic efficacy was evaluated with the poorly permeable BxPC-3 pancreatic carcinoma xenograft model. At a well-tolerated dose of 2 mg/kg, MIT-NPs suppressed BxPC-3 tumor growth by 96%. Compared at an equivalent dose, MIT-NPs exerted significantly higher therapeutic effect than free MIT (86% versus 51%, P<0.01). Moreover, the treatment of MIT and MIT-NPs reduced the expression level of oncogene c-Myc regulated by Sp1, and notably, both of them decreased the protein level of CD47. In summary, the novel formulation of MIT-NPs shows highly therapeutic efficacy against pancreatic carcinoma xenograft. In addition, MIT-NPs can downregulate CD47 expression, implying that it might play a positive role in cancer immunotherapy.

Dataset Information

Humanized bispecific antibody (mPEG?×?HER2) rapidly confers PEGylated nanoparticles tumor specificity for multimodality imaging in breast cancer.

Publications

Humanized bispecific antibody (mPEG × HER2) rapidly confers PEGylated nanoparticles tumor specificity for multimodality imaging in breast cancer.

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