Proteolytic Nanoparticles Replace a Surgical Blade by Controllably Remodeling the Oral Connective Tissue

Abstract

Surgical blades are common medical tools. However, blades cannot distinguish between healthy and diseased tissue, thereby creating unnecessary damage, lengthening recovery, and increasing pain. We propose that surgical procedures can rely on natural tissue remodeling tools-enzymes, which are the same tools our body uses to repair itself. Through a combination of nanotechnology and a controllably activated proteolytic enzyme, we performed a targeted surgical task in the oral cavity. More specifically, we engineered nanoparticles that contain collagenase in a deactivated form. Once placed at the surgical site, collagenase was released at a therapeutic concentration and activated by calcium, its biological cofactor that is naturally present in the tissue. Enhanced periodontal remodeling was recorded due to enzymatic cleavage of the supracrestal collagen fibers that connect the teeth to the underlying bone. When positioned in their new orientation, natural tissue repair mechanisms supported soft and hard tissue recovery and reduced tooth relapse. Through the combination of nanotechnology and proteolytic enzymes, localized surgical procedures can now be less invasive.

Sodium bicarbonate nanoparticles modulate the tumor pH and enhance the cellular uptake of doxorubicin

“…Nanotechnologies are becoming important medical tools, owned to their ability to target therapeutic and diagnostic compounds to diseased tissues with high accuracy [16][17][18][19][20][21][22][23][24][25][26][27]. Specifically, nanoparticles have been shown to accumulate preferentially in solid tumors by extravagating through defects in the endothelial layer of the tumor vasculature, a phenomenon known as the Enhanced Permeation and Retention (EPR) effect [28][29][30][31][32][33][34] Liposomes, self-assembled vesicles, having one or several concentric lipid bilayers, are widely used nanoscale drug delivery systems [35].…”

Prospects of nanodentistry for the diagnosis and treatment of maxillofacial pathologies and cancers

“…The application of nanotechnological principles and materials has redefined the face of oral diagnosis, therapy, surgery, dentistry and maxillofacial pathologies, globally. Nanodentistry has evolved due to the attendant adverse effects and complication attributed to dentistry and its offshoots such as painful and invasive dental surgeries, as well as disfigurement [ 77 ]. In addition, there is also an increased awareness amongst individuals on the need to maintain above average dental hygiene/care for aesthetics and/or enhancement of beauty, to boost physical/facial appearance and confidence [ 76 , 78 ].…”

“…Practical examples of the benefit of nanodentistry, includes the use of empty nano-sized liposome vesicles, for non-invasive drug delivery in dental therapies [ 77 ]. Also, despite current challenges there is hope for NP-delivered enzymes (collagenase) which have a high probability for remodelling periodontal fibres in targeted oral surgery, without the need for scalpel invasion.…”

“…Also, despite current challenges there is hope for NP-delivered enzymes (collagenase) which have a high probability for remodelling periodontal fibres in targeted oral surgery, without the need for scalpel invasion. This promises faster and painless surgery time [ 77 , 79 ]. Other benefits include novel substances for preventative dental care such as dentifrices for dentine and enamel that impart antimicrobial and/or other rejuvenating potentials.…”

Intravital imaging of vascular anomalies and extracellular matrix remodeling in orthotopic pancreatic tumors

“…Liposomes were prepared as described by Zinger et al 23 with slight modification. Briefly, a lipid mixture of hydrogenated soybean phosphatidylcholine (HSPC; Avanti, MW 762 g/mol), cholesterol (Sigma-Aldrich, MW 386 g/mol), 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-lissamine rhodamine B sulfonyl (Rhod-DSPE; Avanti, MW 1,250 g/mol and 1,2-distearoyl-snglycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPE-PEG (2000); Avanti, MW 2,790 g/mol) at a molar ratio of 55.94:39:0.06:5, respectively, were dissolved in absolute ethanol at 70 C. The dissolved lipids were quickly injected into a 1× PBS (Sigma Aldrich, St. Louis, MO) solution at 70 C, to reach a lipid concentration of 50 mM.…”