Journal
CANCER NANOTECHNOLOGY
Volume 14, Issue 1, Pages -Publisher
SPRINGER WIEN
DOI: 10.1186/s12645-023-00230-6
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
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Modification of PLD with CD20-specific mPEG x CD20 enhances the internalization and anti-cancer efficacy of PEG-NPs, improving therapeutic efficacy.
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.
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