Dual-receptor targeted strategy in nanoparticle design achieves tumor cell selectivity through cooperativity

Nanoscale
Jared F StefanickBasar Bilgicer

Abstract

Targeted liposomal nanoparticles are commonly used drug delivery vehicles for targeting cancer cells that overexpress a particular cell surface receptor. However, typical target receptors are also expressed at variable levels in healthy tissue, leading to non-selective targeting and systemic toxicity. Here, we demonstrated that the selectivity of peptide-targeted liposomes for their target cells can be significantly enhanced by employing a dual-receptor targeted approach to simultaneously target multiple tumor cell surface receptors. The dual-receptor targeted approach can be tuned to create cooperativity in binding only for the cancer cells, therefore leaving the healthy cells and tissue unharmed. We evaluated this strategy in a multiple myeloma disease model where the liposomes were functionalized with two distinct peptide antagonists to target VLA-4 and LPAM-1, two receptors with increasing relevance in multiple myeloma. By employing a multifaceted strategy to synthesize dual-receptor targeted liposomes with high purity, reproducibility, and precisely controlled stoichiometry of functionalities, we identified optimal design parameters for enhanced selectivity via systematic analysis. Through control of the liposomal formulat...Continue Reading

References

Aug 2, 1990·Nature·T A Springer
Jan 1, 1991·The Journal of Clinical Investigation·E Ruoslahti
Oct 28, 1997·Journal of Medicinal Chemistry·D Y JacksonS Fong
Jun 6, 2000·Advanced Drug Delivery Reviews·M Willis, E Forssen
Jul 26, 2002·Journal of Medicinal Chemistry·Nathan J P DubreeDavid Y Jackson
Oct 3, 2002·Nature Reviews. Cancer·Theresa M Allen
Jun 20, 2003·Progress in Lipid Research·P Sapra, T M Allen
Aug 16, 2003·Endocrine Reviews·Jean Claude Reubi
Aug 23, 2003·Journal of Controlled Release : Official Journal of the Controlled Release Society·Raymond M SchiffelersGert Storm
Sep 23, 2003·Journal of Controlled Release : Official Journal of the Controlled Release Society·Justin M SaulRavi V Bellamkonda
Feb 3, 2005·Nature Reviews. Drug Discovery·Vladimir P Torchilin
Mar 2, 2005·Nature Reviews. Cancer·Mauro Ferrari
May 4, 2005·Journal of Controlled Release : Official Journal of the Controlled Release Society·Ketan B GhaghadaAnanth V Annapragada
May 21, 2005·Biochimica Et Biophysica Acta·Kimberley LaginhaTheresa Allen
Sep 1, 2005·Journal of the American Chemical Society·Mark L Wolfenden, Mary J Cloninger
Nov 25, 2005·Current Drug Delivery·Puja SapraTheresa M Allen
Aug 15, 2006·Journal of Controlled Release : Official Journal of the Controlled Release Society·Justin M SaulRavi V Bellamkonda
Aug 25, 2006·Molecular Cancer Therapeutics·Rajni SinhaDong M Shin
Nov 15, 2006·Anti-cancer Agents in Medicinal Chemistry·Theresa M AllenKimberley M Laginha
Dec 13, 2006·Chembiochem : a European Journal of Chemical Biology·Robert M OwenLaura L Kiessling
Feb 13, 2007·ACS Chemical Biology·Coby B CarlsonLaura L Kiessling
Feb 12, 2009·ACS Nano·Omid C Farokhzad, Robert Langer
Oct 20, 2009·Trends in Pharmacological Sciences·Yogeshkumar MalamAlexander M Seifalian
Jul 10, 2010·Proceedings of the National Academy of Sciences of the United States of America·Abhimanyu S ParaskarShiladitya Sengupta
Mar 15, 2012·The AAPS Journal·Rupa R Sawant, Vladimir P Torchilin
Apr 10, 2012·Journal of Controlled Release : Official Journal of the Controlled Release Society·Yechezkel Barenholz
Oct 6, 2012·Advanced Drug Delivery Reviews·Theresa M Allen, Pieter R Cullis
Apr 19, 2013·Chemical Communications : Chem Comm·Haihua XiaoBasar Bilgicer
Aug 7, 2013·Nanomedicine·Pranali P DeshpandeVladimir P Torchilin
Nov 12, 2013·Trends in Biotechnology·Gavin T NobleBasar Bilgicer
Jun 5, 2014·Journal of Medicinal Chemistry·Jonathan D AshleyBasar Bilgicer
May 6, 2015·PloS One·Andrew D WongPeter C Searson

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Citations

Aug 29, 2020·Pharmaceutics·Alberto JuanCarlos Alonso-Moreno
Aug 23, 2020·International Journal of Molecular Sciences·Alberto JuanCarlos Alonso-Moreno
Oct 29, 2020·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Mei-Lin ChenYu-Hsin Lin
Oct 31, 2020·Cancers·Daniela IannazzoAlessandra Bitto
Nov 4, 2020·Journal of Hematology & Oncology·David T OmsteadBasar Bilgicer
Mar 14, 2021·Colloids and Surfaces. B, Biointerfaces·Zhongying GongJingkun Bai
Dec 24, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Francesca FontanaGregory M Lanza
Sep 2, 2021·Proceedings of the National Academy of Sciences of the United States of America·Christine LinneDaniela J Kraft
Dec 22, 2021·Integrative Biology : Quantitative Biosciences From Nano to Macro·Zhixin Cyrillus TanAaron S Meyer

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Methods Mentioned

BETA
flow cytometry
Dynamic light scattering
confocal microscopy

Software Mentioned

Nikon Elements Ar

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