Preparation of a mesoporous silica-based nano-vehicle for dual DOX/CPT pH-triggered delivery

Abstract

A dual doxorubicin/camptothecin (DOX/CPT) pH-triggered drug delivery mesoporous silica nanoparticle (MSN)-based nano-vehicle has been prepared. In this drug-delivery system (DDS), CPT is loaded inside the pores of the MSNs, while DOX is covalently attached to the surface of an aldehyde-functionalized MSN through a dihydrazide–polyethylene glycol chain. Thus, DOX and the linker act as pH-sensitive gatekeeper. The system is versatile and easy to assemble, not requiring the chemical modification of the drugs. While at physiological conditions the release of the drugs is negligible, at acidic pH a burst release of DOX and a gradual release of CPT take place. In vitro cytotoxicity tests have demonstrated that this DDS can deliver efficiently DOX and CPT for combination therapy.

Layer-by-layer pH-sensitive nanoparticles for drug delivery and controlled release with improved therapeutic efficacy in vivo

“…Chemotherapy is still the most effective and efficient way to treat cancer in clinic even with the rapid development of nanotechnology recently (Galluzzi et al, 2015;Hallaj-Nezhadi & Hassan, 2015;Gandhi et al, 2018;Srinivasan et al, 2018). A series of chemical anticancer drugs have been well developed and clinically used in these decades, such as doxorubicin (DOX) (Zhang et al, 2012;Fabbri et al, 2016), paclitaxel (PTX) (Markman & Mekhail, 2002;Yang et al, 2018), and camptothecin (CPT) (Venditto & Simanek, 2010;Llin as et al, 2018); however, these drugs are limited in the further clinical applications due to the serious side-effects caused by offtargeting and low therapeutic efficacy (Jungk et al, 2016;Yoshizawa et al, 2016). To overcome these obstacles, nanoscale drug delivery systems (DDSs) have attracted more and more attention and been extensively investigated (Chen et al, 2014), such as polymeric micelles (PMs), nanoparticles (NPs), prodrug, and liposome (Zhang et al, 2016;Zylberberg & Matosevic, 2016;Huang et al, 2018;Li et al, 2018;Dong et al, 2019).…”

Glycyrrhetinic Acid-Functionalized Mesoporous Silica Nanoparticles for the Co-Delivery of DOX/CPT-PEG for Targeting HepG2 Cells

“…Once in the hand of prodrug 1, the DDS was built using regioselectively functionalized amino-aldehyde MSNs. The synthesis of these nanoparticles has been previously reported by our group [5,19] (Tables S1 and S2, Figure S4). Then, CPT-PEG (1) was loaded into the pores of the MSNs using a mixture of CHCl 3 /MeOH (4:1) as solvent.…”

“…MSN-(NH 2 ) CTAB (0.2 g) were mixed with 0.1 g of 2-isothiocyanate-1,1-dimethoxyethane (prepared as described in ref. [5]) (4 eq 0.1 g, 6.8 × 10 −4 mol) in 50 mL of dry toluene. After 24 h, the resulting solid was washed twice with toluene and EtOH.…”

“…Subsequently, an excess of 3,6,9,12,15-pentaoxaheptadecanedihydrazide [5] (Scheme S1) was added to the suspension to render the corresponding mono hydrazone. Then, the unreacted reagent was eliminated by centrifugation to avoid any unwanted reaction in the next step.…”

“…To address these drawbacks, drug delivery systems (DDS) based on nanoparticles (NP) have been proposed. In particular, in the last years, mesoporous silica nanoparticles (MSN) have emerged as effective platforms to prepare smart nano-carriers to ferry drugs with precision to the tumors owing to its outstanding properties such as good biocompatibility, easy chemical modification, and high encapsulation capacity [5][6][7][8][9][10][11][12][13][14][15][16]. These DDSs accumulate selectively into the tumors thanks to the so-called enhanced permeability retention effect (EPR effect) [13,17].…”