Polyglutamic Acid-Gated Mesoporous Silica Nanoparticles for Enzyme-Controlled Drug Delivery

Abstract

Mesoporous silica nanoparticles (MSNs) are highly attractive as supports in the design of controlled delivery systems that can act as containers for the encapsulation of therapeutic agents, overcoming common issues such as poor water solubility and poor stability of some drugs and also enhancing their bioavailability. In this context, we describe herein the development of polyglutamic acid (PGA)-capped MSNs that can selectively deliver rhodamine B and doxorubicin. PGA-capped MSNs remain closed in an aqueous environment, yet they are able to deliver the cargo in the presence of pronase because of the hydrolysis of the peptide bonds in PGA. The prepared solids released less than 20% of the cargo in 1 day in water, whereas they were able to reach 90% of the maximum release of the entrapped guest in ca. 5 h in the presence of pronase. Studies of the PGA-capped nanoparticles with SK-BR-3 breast cancer cells were also undertaken. Rhodamine-loaded nanoparticles were not toxic, whereas doxorubicin-loaded nanoparticles were able to efficiently kill more than 90% of the cancer cells at a concentration of 100 μg/mL.

Polymer‐Brush‐Grafted Mesoporous Silica Nanoparticles for Triggered Drug Delivery

“…Advantages of the enzyme trigger lie in that it can yield rapidly as well as selective targeted drug delivery to cancer cells, leading to improved therapeutic effects . For example, proteases found in the tumor microenvironment have been devoted to enzyme‐mediated DDSs based on polyglutamic acid (PGA) functionalized MSNs (Figure ) . The PGA‐capped MSNs remain closed in an aqueous environment, yet they are able to deliver the cargo in the presence of pronase attributed to the hydrolysis of the peptide bonds in PGA.…”

“…Responsive polymers Synthesis References pH poly(l-histidine) graft to [7] polyaniline graft from [21] poly (acrylic acid) graft to [22] Temperature poly-N-isopropylacrylamide graft from [23] poly(epsilon-caprolactone) graft to [24] poly(ethylene glycol-lactide) graft to [25] Enzyme polyglutamic acid graft from [10] azido-GFLGR 7 RGDS graft to [26] Light azobenzene/b-cyclodextrin graft to [27] 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 controllability over the shape and length of polymers, which is essential for drug delivery and cell targeting. [38]…”

“…[43] For example, proteases found in the tumor microenvironment have been devoted to enzymemediated DDSs based on polyglutamic acid (PGA) functionalized MSNs (Figure 2). [10] The PGA-capped MSNs remain closed in an aqueous environment, yet they are able to deliver the cargo in the presence of pronase attributed to the hydrolysis of the peptide bonds in PGA. The accumulative cargo release amount from the prepared solids was less than 20 % within 1 day in water, while in the presence of pronase, the maximum amount of cargo release could reach to 90 % within 5 h. This suggested that pronase could accelerate the drug release rate and DOXloaded NPs were able to efficiently kill more cancer cells at relatively low concentrations.…”

“…Considerable studies associated with polymer‐based micelles or microspheres, liposomes, silica, titanium dioxide and carbon NPs as stimuli‐responsive drug carriers have been exploited. Among these carriers, MSNs have gained tremendous interest attributed to their remarkable features: (1) MSNs have unique pore characteristics to encapsulate various drugs, overcoming the poor water solubility and stability of drugs and also enhancing their bioavailability; (2) MSNs are biocompatible and can be safely taken up by living cells through endocytosis; (3) their surface active silanol groups make these NPs readily modifiable with different molecules to achieve various functions, e. g., responsive to different stimuli.…”

Mesoporous silica materials for controlled delivery based on enzymes

“…42 In this case, polyglutamic-acid was anchored to the surface of MSNs previously modified with APTES thanks to the formation of amide bonds. In the presence of pronase, peptide bonds were cleaved and remarkable cargo release was observed.…”