Large Pore Mesoporous Silica and Organosilica Nanoparticles for Pepstatin A Delivery in Breast Cancer Cells

Abstract

(1) Background: Nanomedicine has recently emerged as a new area of research, particularly to fight cancer. In this field, we were interested in the vectorization of pepstatin A, a peptide which does not cross cell membranes, but which is a potent inhibitor of cathepsin D, an aspartic protease particularly overexpressed in breast cancer. (2) Methods: We studied two kinds of nanoparticles. For pepstatin A delivery, mesoporous silica nanoparticles with large pores (LPMSNs) and hollow organosilica nanoparticles (HOSNPs) obtained through the sol–gel procedure were used. The nanoparticles were loaded with pepstatin A, and then the nanoparticles were incubated with cancer cells. (3) Results: LPMSNs were monodisperse with 100 nm diameter. HOSNPs were more polydisperse with diameters below 100 nm. Good loading capacities were obtained for both types of nanoparticles. The nanoparticles were endocytosed in cancer cells, and HOSNPs led to the best results for cancer cell killing. (4) Conclusions: Mesoporous silica-based nanoparticles with large pores or cavities are promising for nanomedicine applications with peptides.

Protease-triggered bioresponsive drug delivery for the targeted theranostics of malignancy

“…This chemically stable conjugate could be efficiently ingested by retinal cells and exhibited cathepsin D-accelerated drug release and targeted therapy for ocular diseases. Another approach focused on the vectorization of cathepsin D inhibitors and the interpretation of their structure-function relevance 286 , 287 . For cathepsin E, recent studies emphasized exploring its feasibility as a molecular target for cancer theranostics and developing its clinical application potency 288 .…”

Inorganic Porous Nanoparticles for Drug Delivery in Antitumoral Therapy

“…Rahmani et al. have employed large‐pores MSN to deliver pepstatin A, a potent inhibitor of cathepsin D. [ 71 ] Cathepsin D is a proteolytic enzyme overexpressed in breast cancer which is associated with tumor growth and its inhibition yields valuable antitumoral properties.…”

Folic acid-modified celastrol nanoparticles: synthesis, characterization, anticancer activity in 2D and 3D breast cancer models

“…Firstly, 2.5 lM AuNP, 2.5 lM CA and 2.5 lM FCA nanoparticles were dissolved in 2 ml ethanol solution and 0.5 mM of FITC, then stirred for 24 h at RT. After centrifugation for 20 min at 12,000 rpm, the NPs were washed twice with 1 ml of ethanol and dried under air overnight [10]. 2.5 lM folic acid and 2.5 lM celastrol were not added FITC.…”