pH/H₂O₂ Dual-Responsive Chiral Mesoporous Silica Nanorods Coated with a Biocompatible Active Targeting Ligand for Cancer Therapy

Abstract

Nano-drug delivery systems (nano-DDSs) with an existing specific interaction to tumor cells and intelligent stimulus-triggered drug delivery performance in a tumor microenvironment (TME) remain hotspots for effective cancer therapy. Herein, multifunctional pH/H2O2 dual-responsive chiral mesoporous silica nanorods (HA-CD/DOX-PCMSRs) were creatively constructed by first grafting phenylboronic acid pinacol ester (PBAP) onto the amino-functioned nanorods, then incorporating doxorubicin (DOX) into the mesoporous structure, and finally coating with the cyclodextrin-modified hyaluronic acid conjugate (HA-CD) through a weak host–guest interaction. Under a physiological environment, the gatekeeper CD could avoid the premature leakage of DOX and minimize the side effects to normal cells. After the uptake by the tumor cells, the H2O2-sensitive moieties of PBAP were exposed and a small amount of DOX was leaked along with the shift of the supramolecular switch HA-CD under the acidic condition. Notably, the self-supplying H2O2 mediated by the released DOX in turn accelerated the PBAP disintegration, further promoted the rapid release of DOX, and increased the DOX accumulation in tumor regions. Innovatively, this nano-DDS could simultaneously achieve the tumor-targeting ability via CD44 receptor-mediated endocytosis and pH/H2O2 dual responsiveness activated by the TME and hence exhibited superior antitumor efficacy. Furthermore, HA acting as the hydrophilic shell could improve the biocompatibility of this nano-DDS.

Supramolecular Self-Assemblies with Self-Supplying H2O2 and Self-Consuming GSH Property for Amplified Chemodynamic Therapy

“…Generally, when the substitution of carboxyl groups in HA is less than 25%, the CD44-receptor- mediated endocytosis behavior could be endowed in the cancer therapy. 30 Thus, the synthesized host moiety HA-CD could have active targeting ability. The Fourier transform infrared (FT-IR) spectra of HA, β-CD-EDA, and HA-CD are shown in Figure S1.…”

“…26−28 It is worth noting that after being grafted into the hyaluronic acid (HA), the CD44-receptor-mediated active targeting biomacromolecules, HA-CD, could be obtained and utilized as biodegradable nanocarriers according to the literature. 29,30 Fortunately, ferrocene (Fc), which possessed a single metal atom as the active site and excellent biodegradability, could be included by β-CD to construct supramolecular complexes with a H 2 O 2 -responsive property. 31,32 In addition, Fc is preferable for CDT due to its stability, superior biodegradability, and biocompatibility in contrast to inorganic Fe-based nanoparticles.…”

“…Focusing on these problems, supramolecular polymers, which were endowed with a specific stimuli-responsive property and a dynamic nature, could be considered a favorable candidate for the potential preparation and application of CDT nanoagents. − Specially, host–guest interaction-based supramolecular polymers (HGSPs) have attracted much attention in the cancer treatment fields due to the facile preparation strategy, responsive self-assembly behaviors, and biodegradable property. − As one type of macrocyclic molecules, β-cyclodextrins (β-CD) can include specific guest molecules with appropriate sizes and interactions. − It is worth noting that after being grafted into the hyaluronic acid (HA), the CD44-receptor-mediated active targeting biomacromolecules, HA-CD, could be obtained and utilized as biodegradable nanocarriers according to the literature. , Fortunately, ferrocene (Fc), which possessed a single metal atom as the active site and excellent biodegradability, could be included by β-CD to construct supramolecular complexes with a H 2 O 2 -responsive property. , In addition, Fc is preferable for CDT due to its stability, superior biodegradability, and biocompatibility in contrast to inorganic Fe-based nanoparticles . Thus, CD/Fc-based inclusion interactions could be preferable for CDT to construct specific-responsive and biodegradable supramolecular polymer-based nanoagents.…”

Host–guest interaction-based supramolecular prodrug self-assemblies for GSH-consumption augmented chemotherapy

“…In vitro drug release, cellular uptake and cytotoxicity study Supramolecular drug delivery nano-systems, which can respond to the tumor microenvironment, have gained considerable attention in the chemotherapy process to enhance the bioavailibility of chemical drugs, and avoid the side effects to normal tissues. [37][38][39][40] Thus, the controlled drug release behaviors of target SPSAs-2 were first studied. The in vitro drug release behavior of Cb and Cur from SPSAs-2 was investigated by HPLC under the conditions of pH 7.4, pH 5.0, pH 5.0 with H 2 O 2 (1 mM) at 37 1C.…”

Probiotic Engineering and Targeted Sonoimmuno‐Therapy Augmented by STING Agonist

“…for passive targeting transportation through enhanced permeability and retention effect. These approaches could not only substantially prolong the plasma half terminal life of the small molecule sonosensitizers, but also impart the stimuli‐responsive characters (e.g., pH‐responsive, [ 6 ] GSH‐responsive, [ 7 ] H 2 O 2 responsive, [ 8 ] etc.) within the lesion tissue based on the specific microenvironment.…”