Modulating the Selectivity and Stealth Properties of Ellipsoidal Polymersomes through a Multivalent Peptide Ligand Display

Abstract

There is a need for improved nanomaterials to simultaneously target cancer cells and avoid nonspecific clearance by phagocytes. We developed an ellipsoidal polymersome system with a unique tunable size and shape property. These particles were functionalized with our in-house phage-display cell-targeting peptide to target a medulloblastoma cell line in vitro. Particle association with medulloblastoma cells was modulated by tuning the peptide ligand density on the particles. These polymersomes had low levels of association with primary human blood phagocytes. The stealth properties of the polymersomes were further improved by including the peptide targeting moiety, an effect that was likely driven by the peptide protecting the particles from binding blood plasma proteins. Overall, this ellipsoidal polymersome system provides a promising platform to explore tumor cell targeting in vivo.

Intelligent design of polymersomes for antibacterial and anticancer applications

“…(c) Peptide‐conjugated targeting polymersome. Reprinted with permission from Tjandra et al (2020), Copyright 2020 2020 2020 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.…”

“…Peptides with specific short sequence can bind to overexpressed proteins such as transferrin and integrin on the membrane of cancer cells, and exhibit enhanced cell penetration. These peptides can be covalently conjugated to polymersomes, and show significant targeting ability (Oz et al, 2021; Pangburn et al, 2012; Tjandra et al, 2020). Oz and co‐workers designed an integrin‐targeted polymersome based on a tumor homing peptide sequence‐WREAAYQRFL (Oz et al, 2021).…”

“…Then, the peptide‐conjugated polymer was assembled to form polymersome and anticancer drug DOX was encapsulated into polymersome during self‐assembly process. Tjandra and co‐workers synthesized another kind of targeting peptide‐conjugated polymersomes as targeted delivery system (Tjandra et al, 2020). As shown in Figure 8c, a cell‐penetrating heptapeptide FSRPAFL, which showed selectivity and high binding affinity for human medulloblastoma cells, was link to amphiphilic copolymer via the reaction between pentafluorophenyl ester group on the polymer and the N ‐terminus on the peptide.…”

“…Targeted delivery of anticancer drugs is one of the most promising ways to overcome anticancer drug resistance in cancer. Targeted drug delivery nano‐platforms including hydrogels (Chen, Wang, et al, 2020b; Zhao et al, 2020), micelles (Wang et al, 2017; Yin et al, 2019), polymersomes (Tjandra et al, 2020; Wei, Gu, et al, 2020b), and nanospheres (Huang et al, 2019; Park et al, 2022) have been widely investigated. These drugs loaded nano‐platforms deliver drugs into cancer cells by endocytosis to prevent efflux pump or altered membrane permeability, thus to realize increased drug accumulation in cancer cells.…”

Nonspherical Nanocapsules as Long-Circulating Drug Delivery Systems

“…The formation of ellipsoidal polymersomes via a solvent-switch method using the block copolymer, PEG 43 -b-P(NIPAM 21 -co-PDMI 9 ) (Figure 18a) has been reported. 68 The perylene moiety in the polymer provided the hydrophobicity and liquid crystallinity for the polymer to self-assemble into the ellipsoidal shape (Figure 18a). 102 The ellipsoidal shape was formed through a solvent-switch method with tetrahydrofuran (THF) as the good solvent and water as the antisolvent.…”