Cancer Nanotechnology (Oct 2023)

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

  • Huei-Jen Chen,
  • Yi-An Cheng,
  • Yu-Tung Chen,
  • Chia-Ching Li,
  • Bo-Cheng Huang,
  • Shih-Ting Hong,
  • I.-Ju Chen,
  • Kai-Wen Ho,
  • Chiao-Yun Chen,
  • Fang-Ming Chen,
  • Jaw-Yuan Wang,
  • Steve R. Roffler,
  • Tian-Lu Cheng,
  • Dung-Ho Wu

DOI
https://doi.org/10.1186/s12645-023-00230-6
Journal volume & issue
Vol. 14, no. 1
pp. 1 – 17

Abstract

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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 × CD20) which was able to simultaneously bind to methoxy PEG on liposomes and CD20 to form multivalent αCD20-armed liposomes. This αCD20-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 × CD20 and used this bispecific antibody to modify PEGylated liposomal doxorubicin (PLD) through a one-step formulation. Results αCD20-armed PLD (αCD20/PLD) specifically targeted CD20+ Raji cells and enhanced PLD internalization 56-fold after 24 h. αCD20/PLD also increased cytotoxicity to Raji cells by 15.2-fold in comparison with PLD and control mPEG × DNS-modified PLD (αDNS/PLD). mPEG × CD20 significantly enhanced the tumor accumulation 2.8-fold in comparison with mPEG × DNS-conjugated PEGylated liposomal DiD in Raji tumors. Moreover, αCD20/PLD had significantly greater therapeutic efficacy as compared to αDNS/PLD (P < 0.0001) and PLD(P < 0.0001), and αCD20/PLD-treated mice had a 90% survival rate at 100-day post-treatment. Conclusions Modification of mPEG × 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.

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