Loading cisplatin onto 6-mercaptopurine covalently modified MSNS: a nanomedicine strategy to improve the outcome of cisplatin therapy

Abstract

In the treatment of cancer patients, cisplatin (CDDP) exhibits serious cardiac and renal toxicities, while classical combinations related to CDDP are unable to solve these problems and may result in worse prognosis. Alternately, this study covalently conjugated 6-mercaptopurine (6MP) onto the surface of mercapto-modified mesoporous silica nanoparticles (MSNS) to form MSNS-6MP and loaded CDDP into the holes on the surface of MSNS-6MP to form MSNS-6MP/CDDP, a tumor-targeting nano-releasing regime for CDDP and 6MP specifically. In the S180 mouse model, the anti-tumor activity and overall survival of MSNS-6MP/CDDP (50 mg·kg−1·day−1, corresponding to 1 mg·kg−1·day−1 of 6MP and 5 mg·kg−1·day−1 of CDDP) were significantly higher than those of CDDP alone (5 mg·kg−1·day−1) or CDDP (5 mg·kg−1·day−1) plus 6MP (1 mg·kg−1·day−1). The assays of serum alanine aminotransferase, aspartate aminotransferase and creatinine, as well as the images of myocardium and kidney histology, support that MSNS-6MP/CDDP is able to completely eliminate liver, kidney and heart toxicities induced by CDDP alone or CDDP plus 6MP.

Pt and Ti Complexes Immobilized onto Mesoporous Silica Microspheres and Their Interaction with Molecules of Biological Interest

“…Huang et al used mesoporous silica nanoparticles as carriers with a high density of carboxylic groups inside their mesopores to load hydrophilic Pt II drugs through chelation . A similar strategy has been followed by Lv et al who tested mercaptopurine‐modified mesoporous silica nanoparticles as nanocarriers of cisplatin, and by Balkus and co‐workers who designed nitric‐oxide‐ and cisplatin‐releasing wrinkle‐structured amine‐modified mesoporous silica nanoparticles . A more sophisticated system has been published by Mohapatra et al who synthesized hollow mesoporous silica nanospheres; the exterior was selectively functionalized with carboxylic groups to conjugate cisplatin, folic acid and rhodamine isothiocyanate, whereas the interior space was used to encapsulate superparamagnetic nanoparticles as well as the hydrophobic anticancer drug pemetrexed .…”

A Study on Mesoporous Silica Loaded With Novel Photosensitizers HCE6 and Oxaliplatin for the Treatment of Cholangiocarcinoma

“…Moreover, MSN also exhibit a superior ability in controlling drug release due to the simple attachment of drugs in the mesopores, and the adjustable size and shape of the mesopores. Lv et al (24) revealed in their study that MSNs loading was effective in reducing the toxic effects of cisplatin on the heart, liver, and kidneys of patients as well as the adverse effects during chemotherapy in cancer patients. In this study, OH-MSNs drug delivery system was synthesized using MSNs loaded with Oxaliplatin and photosensitizer HCE6, and a novel dosing strategy was proposed.…”

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

“…Attention to the method of drug loading was also drawn and in order to avoid undesirable reactions of cisplatin with DMSO [70], the solvent was eliminated in synthetic approach. Zhao et al applied a combination strategy by covalent attachment of 6-mercaptopurine (6MP) to the surface of MSN and loading cisplatin into the pores of modified silica carrier [71], containing thiol groups (Figure 20). The contents of cisplatin in the MSN-6MPcisplatin system was 100 mg/1 g (1 g of MSNS-6MP-cispltin contained 100 mg of cisplatin).…”