Nanoarchitectonics: Complexes and Conjugates of Platinum Drugs with Silicon Containing Nanocarriers. An Overview

Abstract

The development in the area of novel anticancer prodrugs (conjugates and complexes) has attracted growing attention from many research groups. The dangerous side effects of currently used anticancer drugs, including cisplatin and other platinum based drugs, as well their systemic toxicity is a driving force for intensive search and presents a safer way in delivery platform of active molecules. Silicon based nanocarriers play an important role in achieving the goal of synthesis of the more effective prodrugs. It is worth to underline that silicon based platform including silica and silsesquioxane nanocarriers offers higher stability, biocompatibility of such the materials and pro-longed release of active platinum drugs. Silicon nanomaterials themselves are well-known for improving drug delivery, being themselves non-toxic, and versatile, and tailored surface chemistry. This review summarizes the current state-of-the-art within constructs of silicon-containing nano-carriers conjugated and complexed with platinum based drugs. Contrary to a number of other reviews, it stresses the role of nano-chemistry as a primary tool in the development of novel prodrugs.

Keywords: anticancer platinum drugs; nanocomplexes synthesis and properties; nanoconjugates; silicon containing nanocarriers.

Scheme 1

Illustration of silicon-containing constructs nanocarriers conjugated and complexed with platinum-based drugs.

Figure 1

Platinum(II) anticancer drugs (a) cislatin, (b) oxaliplatin, (c) carboplatin.

Figure 2

Basic platinum(IV) synthons applied in preparation of nanoconjugates (a–c).

Figure 3

Pt(IV)-based prodrug consisting of square-planar cisplatin and two axial ligands, X. The two electron reduction to square-planar Pt(II), with loss of the axial ligands, is also shown (a). Scheme of the reduction potential-responsive cisplatin release from a prodrug-MSN carrier is presented, FITC -fluorescein isothiocyanate (b) [38].

Figure 4

Tailor-made synthesis of mesoporous silica nanoparticles for platinum(IV) prodrug delivery and glutathione or sodium ascorbate (SA) induced reduction process to Pt(II) in tumor environment [22].

Figure 5

Schematic illustration of platinum nanoconjugate for tri-model high-performance tumour therapy [42].

Figure 6

Scheme of NIR activation of platinum (IV) prodrug grafted on up conversion luminescent nanoparticles (UCNPs@SiO₂) [44].

Figure 7

Schematic illustration of the synthesis and drug release behaviour of Pt@PAA-MSNDOX [46].

Figure 8

Preparation of nanoparticles with SiO₂ core and poly(acrylic acid) shell (PAA-MSN) [46,47,48].

Figure 9

In vitro viability studies of A357 and HeLa cells against free single drugs, Pt@PAA-MSN, PAA-MSNDOX and Pt@PAA-MSNDOX: (a) A357 cells incubated for 24 h; (b) HeLa cells incubated for 24 h; (c) A357 cells incubated for 48 h; (d) HeLa cells incubated for 48 h [46].

Figure 10

Synthesis of magnetic mesoporous silica nanoparticles functionalised with triethoxy-3-(2-imidazoline-1-yl)propylsilane and release of platinum drug [49].

Figure 11

Synthetic scheme of CoFe₂O₄ encapsulating silica NPs [50].

Figure 12

Functionalization of silica nanoparticles with iminodiacetic acid and the conjugation with Pt-drug, FA and RITC [50].

Figure 13

Modification of 1,2-bidentate carboxyl groups onto the parent nanoparticles of MSN-SH via thiol-ene click reaction (A); MSN nanoparticles conjugated with the oxaliplatin active species and the intracellular release of platinum drugs via acid mediated hydrolysis to inhibit the replication of DNA (B) [51].

Figure 14

Scheme of the Fe₃O₄@SiO₂@Au NPs biofunctionalization process and process of the cPt immobilization [52].

Figure 15

Raman spectra of: cisplatin (black spectrum), the pure MHDA (red spectrum), the Au NPs + MHDA (blue spectrum), Fe₃O₄@-SiO₂@Au + MHDA + cisplatin (green spectrum). There is a mistake in the figure as the value for C=O differs from the one in the text in both papers [52,53].

Figure 16

Synthetic and release scheme for cisplatin-polysilsesquioxane system [18].

Figure 17

Preparation of nitric oxide-cisplatin loaded amine-functionalized mesoporous silica [64].

Figure 18

Platinum loaded mesoporous SiO₂ modified with PEG and PEI [68].

Figure 19

Modification of MSNs via (a) surface grafting of carboxylic groups (MSN-COOH) by postsynthetic modification with TESP, (b) coating of PEG and PEI by amidation (c) co-condensation with MPTES leading to MSN-SH. R = −(C₃H₆)SH and R′ = −(OCH₂CH₃)₃ [69].

Figure 20

Schematic synthesis of MSNS-6MP-cisplatin [71].

Figure 21

One-pot synthetic pathway of polymer-gatekeeper MSN with stimuli responsive polymer (PEG-PDS) and targeting ligand (cRGDfC) [72].

Figure 22

Preparation of organic/inorganic hybrid MSN coated with P(DMA-co-TPAMA)/PAH polyelectrolyte multilayers and the pH-triggered dual release of cisplatin adsorbed within multilayers [73].

Figure 23

Scheme of cisplatin loading and CP release [74].

Figure 24

Platinum drugs loaded holmium-165-containing, wrinkled mesoporous silica nanoparticles DOPC lipid coated [63].

Figure 25

Pt NCs-pSiNTs structure [76].

Figure 26

Cytotoxicity of (A) Pt NCs (3.5 ± 1.1 nm) and (B) K₂PtCl₄ at different doses [76].

Figure 27

Synthetic steps for preparation of silicasomes incorporating platinum drugs [77].

Figure 28

Preparation of silica nano-carrier with targeting agent and release of cisplatin [83].

Figure 29

Synthetic scheme for preparation of CDDP@PSNs-C-B₁₂ nanoparticles [85].

Figure 30

Dual delivery of HNF4α and cisplatin by mesoporous silica nanoparticles [91].

Figure 31

Synthetic scheme for multifunctional double mesoporous silica and schematic loading and release of the drugs and protein [92].

Figure 32

Synthesis of cisplatin-collagen “intelligent” MSN and its action towards normal and cancer cells (A549) [97].

Figure 33

Cytotoxicity towards HeLa cell line of AlClPc-MSNs (dark blue), cisplatin-MSNs (dark red), AlClPc/cisplatin-MSNs (dark green) and physical mixture of cisplatin/AlClPc molecules (dark orange) under dark conditions. Phototoxicity of AlClPc-MSNs (light blue), cisplatin-MSNs (light red), AlClPc/cisplatin-MSNs (light green) and physical mixture of cisplatin/AlClPc molecules (light orange) after red light exposure (570–690 nm; 89 mW/cm²) for 20 min [99]. Asterisk indicates p < 0.05.

Figure 34

Preparation and action scheme of the system designed for combination chemotherapy and photodynamic therapy in cancer treatment [99].

Figure 35

Schematic presentation of CuFe₂O₄/HYPS/cisplatin system [100].

Figure 36

Scheme of the synthesis of the magnetic drug delivery nano-system—Fe₃O₄–CDDP [104].

Figure 37

Functionalized polyamide membrane (PA TEOS CPTES) and its preparation [104].

Figure 37

Functionalized polyamide membrane (PA TEOS CPTES) and its preparation [104].

Figure 38

Cell viability assay of GM07492A cell line after treatment with PA TEOS CPTES incorporated with cis-DDP (0.37–766.64 μM) [104].