Smart Self-Assembled Nanosystem Based on Water-Soluble Pillararene and Rare-Earth-Doped Upconversion Nanoparticles for pH-Responsive Drug Delivery

Abstract

Exploring novel drug delivery systems with good stability and new structure to integrate pillararene and upconversion nanoparticles (UCNPs) into one system continues to be an important challenge. Herein, we report a novel preparation of a supramolecular upconversion nanosystem via the host-guest complexation based on carboxylate-based pillar[5]arene (WP5) and 15-carboxy-N,N,N-trialkylpentadecan-1-ammonium bromide (1)-functionalized UCNPs to produce WP5⊃1-UCNPs that can be loaded with the chemotherapeutic drug doxorubicin (DOX). Importantly, the WP5 on the surface of the drug-loaded nanosystem can be efficiently protonated under acidic conditions, resulting in the collapse of the nanosystem and drug release. Moreover, cellular uptake confirms that the nanosystem can enter human cervical cancer (HeLa) cells, resulting in drug accumulation in the cells. More importantly, cytotoxicity experiments demonstrated the excellent biocompatibility of WP5⊃1-UCNPs without loading DOX and that the nanosystem DOX-WP5⊃1-UCNPs exhibited an ability of killing HeLa cells effectively. We also investigated magnetic resonance imaging and upconversion luminescence imaging, which may be employed as visual imaging agents in cancer diagnosis and treatment. Thus, in the present work, we show a simple yet powerful strategy to combine UCNPs and pillar[5]arene to produce a unified nanosystem for dual-mode bioimaging-guided therapeutic applications.

Designing Stimuli‐Responsive Upconversion Nanoparticles that Exploit the Tumor Microenvironment

“…[ 27 ] Li et al demonstrated the multifunctional application of pillar[5]arene (WP5), 15‐carboxy‐ N , N , N ‐trialkylpentadecan‐1‐ammonium bromide 1) and DOX‐conjugated UCNPs in pH‐responsive drug delivery and bio‐imaging to achieve cancer theranostics. [ 28 ] In summary, reports by several groups have demonstrated the modification of UCNPs toward pH‐responsive drug delivery systems (DDS) that can be used in cancer theranostics.…”

Recent Advances in Functional‐Polymer‐Decorated Transition‐Metal Nanomaterials for Bioimaging and Cancer Therapy

“…Recently, Sun et al. outlined the design of a pH‐responsive DDS (WP5⊃1‐UCNPs) for imaging‐guided chemotherapy by integrating upconversion nanoparticles (NaYF 4 :Yb/Er@NaGdF 4 ) and pillararene (WP5) into one nanosystem . This DDS shows favorable water stability, biocompatibility, drug delivery, and imaging properties.…”

A Self-Assembled AMF-Responsive Nanoplatform Based on Pillar[5]arene and Superparamagnetic Nanoparticles for Controlled Release of Doxorubicin

“…30,31 The electron-rich cavity and possible chemical modification on the upper and lower rims of P[n]A can provide very useful water-soluble macrocycles with hydrophobic voids. 32 Thus, anionic and cationic watersoluble pillar[n]arenes have been widely explored as hosts for chemotherapeutic drugs 33,34 as well as micelles, 35,36 vesicles, [36][37][38][39][40][41] and gatekeepers in nanovalve systems. [42][43][44][45][46][47] To the best of our knowledge, the combination of watersoluble carboxylate-substituted pillar [5]arene (CP [5]A) grafted onto SPIONs as an AMF stimuli-responsive nanodevice for drug delivery has not been described in the literature.…”