Targeting and internalizing PEGylated nanodrugs to enhance the therapeutic efficacy of hematologic malignancies by anti-PEG bispecific antibody (mPEG x CD20)

doi:10.1186/s12645-023-00230-6

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Title:	Targeting and internalizing PEGylated nanodrugs to enhance the therapeutic efficacy of hematologic malignancies by anti-PEG bispecific antibody (mPEG x CD20)
Authors:	Chen, Huei-Jen Cheng, Yi-An Chen, Yu-Tung Li, Chia-Ching Huang, Bo-Cheng Hong, Shih-Ting Chen, I. -Ju Ho, Kai-Wen Chen, Chiao-Yun Chen, Fang-Ming Wang, Jaw-Yuan Roffler, Steve R. Cheng, Tian-Lu Wu, Dung-Ho
Contributors:	Kaohsiung Med Univ, Dept Biomed Sci & Environm Biol Kaohsiung Med Univ, Grad Inst Med, Coll Med Kaohsiung Med Univ, Drug Dev & Value Creat Res Ctr Kaohsiung Med Univ Hosp, Dept Med Res Kaohsiung Med Univ Hosp, Dept Med Imaging Kaohsiung Med Univ, Coll Med, Sch Postbaccalaureate Med Kaohsiung Med Univ Hosp, Dept Surg, Div Breast Oncol & Surg Kaohsiung Municipal Tatung Hosp, Dept Gen Surg Kaohsiung Med Univ, Coll Med, Fac Med, Dept Surg Acad Sinica, Inst Biomed Sci Chia Nan Univ Pharm & Sci I Shou Univ, Sch Chinese Med Postbaccalaureate
Keywords:	PEGylated nanoparticles (PEG-NPs) Enhanced permeability and retention effect (EPR effect) Anti-PEG bispecific antibody (BsAb mPEG x CD20) CD20-armed liposomes alpha CD20/PLD Hematologic malignancies
Date:	2023
Issue Date:	2024-12-24 18:00:05 (UTC+8)
Publisher:	SPRINGER WIEN
Abstract:	Background: PEGylated nanoparticles (PEG-NPs) are not effective for hematologic malignancies as they lack the enhanced permeability and retention effect (EPR effect). Tumor-targeted PEG-NPs can systemically track lymphoma and actively internalize into cancer cells to enhance therapeutic efficacy. We generated an anti-PEG bispecific antibody (BsAb; mPEG x CD20) which was able to simultaneously bind to methoxy PEG on liposomes and CD20 to form multivalent alpha CD20-armed liposomes. This alpha CD20-armed liposome was able to crosslink CD20 on lymphoma cells to enhance cellular internalization and the anti-cancer efficacy of the liposomes to lymphoma. We generated mPEG x CD20 and used this bispecific antibody to modify PEGylated liposomal doxorubicin (PLD) through a one-step formulation.Results: alpha CD20-armed PLD (alpha CD20/PLD) specifically targeted CD20+ Raji cells and enhanced PLD internalization 56-fold after 24 h. alpha CD20/PLD also increased cytotoxicity to Raji cells by 15.2-fold in comparison with PLD and control mPEG x DNS-modified PLD (alpha DNS/PLD). mPEG x CD20 significantly enhanced the tumor accumulation 2.8-fold in comparison with mPEG x DNS-conjugated PEGylated liposomal DiD in Raji tumors. Moreover, alpha CD20/PLD had significantly greater therapeutic efficacy as compared to alpha DNS/PLD (P < 0.0001) and PLD(P < 0.0001), and alpha CD20/PLD-treated mice had a 90% survival rate at 100-day post-treatment.Conclusions: Modification of mPEG x CD20 can confer PLD with CD20 specificity to enhance the internalization and the anti-cancer efficacy of PEG-NPs. This therapeutic strategy can conveniently be used to modify various PEG-NPs with anti-PEG BsAb to overcome the lack of EPR effect of hematologic malignancies and improve therapeutic efficacy.
Relation:	Cancer Nanotechnology, v.14, n.1, Article 78
Appears in Collections:	[Dept. of Pharmacy] Periodical Articles

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