Polymeric Nanomedicine with “Lego” Surface Allowing Modular Functionalization and Drug Encapsulation

Abstract

Surface functionalization of nanoparticles (NPs) is of pivotal importance in nanomedicine. However, current strategies often require covalent conjugation that involves laborious design and synthesis. Herein, cucurbit[7]uril (CB[7])-decorated poly(lactic acid) (PLA)/poly(lactic-co-glycolic acid) (PLGA) NPs are developed and exploited for the first time as a novel, biocompatible, and versatile drug delivery platform with a noncovalently tailorable surface. CB[7] on the surface of NPs, acting as a "Lego" base block, allowed facile, modular surface modification with a variety of functional moieties or tags that are linked with amantadine (a complementary "Lego" piece to the base block), including amantadine-conjugated folate, polyethylene glycol, and fluorescein isothiocyanate. In addition, surface CB[7] also provided an opportunity for encapsulation of a secondary drug, such as oxaliplatin, into the cavity of the base block CB[7], in addition to a primary drug (e.g., paclitaxel) loaded into PLA/PLGA NPs, for a possible synergistic chemotherapy. This proof of concept not only provides the first versatile PLA/PLGA nanomedicine platform with "Lego" surface for modular functionalization and improved drug delivery but also offers new insights into the design and development of novel nanomedicine with a modular surface.

Macrocyclic Amphiphiles for Drug Delivery

“…al. reported a coassemble of an CB[7]‐decorated poly(lactic acid) CB3 and poly(lactic‐co‐glycolic acid) (PLGA) based NPs as a novel drug delivery platform . A hydrophobic anticancer drug PTX was loaded into the NPs.…”

“…reported a coassemble of an CB[7]decorated poly(lactic acid) CB3 and poly(lactic-co-glycolic acid) (PLGA) based NPs as a novel drug delivery platform. [68] A hydrophobic anticancer drug PTX was loaded into the NPs. Furthermore, CB3 on the surface of the NPs allowed facile, modular surface modification by a variety of functional moieties or tags that are linked with amantadine: folateamantadine (FA-ADA) were able to target to folate receptor overexpressed cell line; fluorescein isothiocyanate-amantadine (FA-ADA) was used to fluorescence trackable delivery in cells; PEG-amantadine (PEG-ADA) can decrease phagocytosis by macrophage; and oxaliplatin (OX) for synergistic therapy against cancer cells (Figure 18).…”

Supramolecular Chemistry in Solid State Materials such as Metal‐Organic Frameworks

“…Nevertheless, the heterogeneization of the recognition properties can be achieved not only by CDs, but also by other type of hosts. For example, it was demonstrated that cucurbit[7]uril (CB[7]), can be used to decorate polylactic acid (PLA) and poly(lactic‐ co ‐glycolactic) acid (PLGA) nanoparticles . This CB[7] addition provides to the particles with specific recognition sites for the loading of secondary drugs such as oxaliplatin, turning this nanoparticles into a biocompatible and versatile drug delivery platform.…”

Ultrastable and Versatile Layer‐by‐Layer Coating Based on Kinetically Trapped Host–Guest Complexation for Mesoporous Silica Nanoparticles

“…[12,[15][16][17][18][19][20][21] Supramolecular strategy has been widely used to construct biomaterials for therapeutic or bioimaging purpose. [22][23][24][25][26][27][28][29][30][31] One key challenge for supramolecular strategy is the stability under PAA via ester and amide linkers to yield PAA-CB [6] and PAA-CPMA, respectively (Figure 1b). MSN was functionalized by CPMA-moiety with GSH-cleavable disulfide linkers.…”