Silica–Calix Hybrid Composite of Allyl Calix[4]arene Covalently Linked to MCM-41 Nanoparticles for Sustained Release of Doxorubicin into Cancer Cells

Abstract

An inorganic–organic hybrid material, MCM-allylCalix, was synthesized by covalent modification of an MCM-41 surface with a tetra-allyl calixarene conjugate. The synthesized hybrid was characterized by 13C and 29Si MAS–NMR, Fourier transform infrared (FT-IR), Brunauer–Emmett–Teller surface area, thermogravimetric analysis (TGA), and transmission electron microscopy (TEM) analyses. The application of this MCM-allylCalix hybrid has been demonstrated for loading and in vitro release of doxorubicin (Dox) in phosphate-buffered saline (PBS) buffer as well as in the cancer cells, viz., MCF7, HeLa, and MDA-MB231. The Dox-loaded hybrid, MCM-allylCalix-Dox, was characterized by TEM, FT-IR, TGA, N2 sorption, diffuse refectance spectroscopy–UV, and fluorescence microscopy to confirm the presence of the drug. The release study of the drug from MCM-allylCalix-Dox was carried out in PBS buffer at pH 5 and 7.4. The results showed ∼140% increase in the release of Dox at pH 5 compared to that at pH 7.4 in 144 h, suggesting a pH-triggered release of the drug. MCM-allylCalix-Dox releases a greater amount of Dox compared to that released from unmodified MCM-Dox. Cytotoxicity studies suggested that MCM-allylCalix-Dox exhibits anticancer activity that is dependent on the nature of the cell. The Dox-loaded hybrid shows more cytotoxicity for MCF7 compared to that for the HeLa and MDA-MB231 cells. This was further supported by ∼120% more internalization of Dox into MCF7 cells compared to that in the other two cell lines. Both fluorescence microscopy and fluorescence-activated cell sorting studies suggested concentration-dependent internalization of Dox into the MCF7 and HeLa cells. The results suggested that the inorganic–organic hybrid can be useful in sustained drug delivery into cancer cells.

Calixarene-Assisted Pd Nanoparticles in Organic Transformations: Synthesis, Characterization, and Catalytic Applications in Water for C–C Coupling and for the Reduction of Nitroaromatics and Organic Dyes

“…The synthesis and characterization of upper-rim allylCalix were carried out in three steps starting from p - tert -butyl calix[4]arene by following our previously reported procedure as given in the Supporting Information SI01. 18 Yield = 91%; 1 H NMR: (400 MHz, CDCl 3 , δ): 10.15 (s, 4H), 6.84 (s, 8H), 5.89 (m, 4H), 5.04 (d, J = 17.0 Hz, 4H), 5.03 (d, J = 17.0 Hz, 4H), 4.19 (d, J = 9.0 Hz, 4H), 3.45 (d, J = 9.0 Hz, 4H), 3.18 (d, J = 6.8 Hz, 8H). 13 C NMR (CDCl 3 ; 100MHz; δ, ppm): 31.81 (Ar–CH 2 –Ar), 39.34 (Ar–CH 2 ), 115.59, 128.20 (—CH=CH 2 ) 128.98, 133.47, 137.61, 147.07 (Ar–C).…”

“…The synthesis of MCM-allylCalix was carried out by following the procedure 18 reported by us as given in the Supporting Information SI01. Yield = 378 mg. EDS elemental analysis: C = 25.9%, O = 53.1%, Si = 21%.…”

“…14−17 Recently, we have reported a tetraallyl calixarene (allylCalix) conjugate that is covalently functionalized on to the mesoporous silica NPs (MCM-allylCalix) and demonstrated its drug storage and delivery aspects. 18 In the present case, the same MCM-allylCalix is utilized for the synthesis of Pd(0) NPs by sacrificial oxidation of a calixarene conjugate resulting in Pd@MCM-Calix ox . The resulting ternary hybrid possesses a hydrophobic calixarene conjugate, a heterogeneous surface, and the capability to reduce.…”

Recent progress to construct calixarene-based polymers using covalent bonds: synthesis and applications

“…As shown by the results, the inorganic-organic hybrid can be used for sustained drug delivery to cancer cells. 108 The p-tert-butyl calix [4]arene mesoporous silica molecular sieves were prepared by Huang et al They also studied diethylstilbestrol and bisphenol A adsorption. 109 Li et al tried to prepare and assess a new calix [4]arene-bonded silica gel stationary phase for HPLC.…”

Design, Preparation, and Characterization of Novel Calix[4]arene Bioactive Carrier for Antitumor Drug Delivery

“…By taking advantage of supramolecular drug delivery system, the loading or release of drugs can be controlled precisely Drug carrier system based on supramolecules has gradually become an emerging area of interest. Supramolecular host compounds mainly include cucurbituril (Plumb et al, 2012; Isaacs, 2014; Oun et al, 2014; Assaf and Nau, 2015; Barrow et al, 2015; Chen et al, 2017), Pillararene (Duan et al, 2013; Wheate et al, 2016; Huang et al, 2017; Li et al, 2017; Cheng et al, 2019) cyclodextrin (Lu et al, 2015; Bhunia et al, 2018), crown ether (Kumbhat and Singh, 2018) and calixarene (Narkhede et al, 2018). Calixarenes, which are formed by condensation of multiple phenol units and formaldehyde, are considered to represent the third-generation of host-guest supramolecular chemistry.…”