title: Bromelain surface modification increases the diffusion of silica nanoparticles in the tumor extracellular matrix.
abstract: Tumor extracellular matrix (ECM) represents a major obstacle to the diffusion of therapeutics and drug delivery systems in cancer parenchyma. This biological barrier limits the efficacy of promising therapeutic approaches including the delivery of siRNA or agents intended for thermoablation. After extravasation due to the enhanced penetration and retention effect of tumor vasculature, typical nanotherapeutics are unable to reach the nonvascularized and anoxic regions deep within cancer parenchyma. Here, we developed a simple method to provide mesoporous silica nanoparticles (MSN) with a proteolytic surface. To this extent, we chose to conjugate MSN to Bromelain (Br-MSN), a crude enzymatic complex, purified from pineapple stems, that belongs to the peptidase papain family. This surface modification increased particle uptake in endothelial, macrophage, and cancer cell lines with minimal impact on cellular viability. Most importantly Br-MSN showed an increased ability to digest and diffuse in tumor ECM in vitro and in vivo.
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute , Houston, Texas 77030, United States.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Parodi
authors.forename: Seth G
authors.initials: SG
authors.lastname: Haddix
authors.forename: Nima
authors.initials: N
authors.lastname: Taghipour
authors.forename: Shilpa
authors.initials: S
authors.lastname: Scaria
authors.forename: Francesca
authors.initials: F
authors.lastname: Taraballi
authors.forename: Armando
authors.initials: A
authors.lastname: Cevenini
authors.forename: Iman K
authors.initials: IK
authors.lastname: Yazdi
authors.forename: Claudia
authors.initials: C
authors.lastname: Corbo
authors.forename: Roberto
authors.initials: R
authors.lastname: Palomba
authors.forename: Sm Z
authors.initials: SZ
authors.lastname: Khaled
authors.forename: Jonathan O
authors.initials: JO
authors.lastname: Martinez
authors.forename: Brandon S
authors.initials: BS
authors.lastname: Brown
authors.forename: Lucas
authors.initials: L
authors.lastname: Isenhart
authors.forename: Ennio
authors.initials: E
authors.lastname: Tasciotti
mesh_terms: D001963:Bromelains / Q000737:chemistry*; D004058:Diffusion; D005109:Extracellular Matrix / Q000737:chemistry*; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D009369:Neoplasms / Q000098:blood supply / Q000737:chemistry* / Q000473:pathology; D012822:Silicon Dioxide / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties
chemical_list: D012822:Silicon Dioxide; D001963:Bromelains
keywords: Bromelain; cancer; cellular uptake; extracellular matrix digestion; mesoporous silica nanoparticle modification