PMID- 25119793 OWN - NLM STAT- MEDLINE DCOM- 20150930 LR - 20231110 IS - 1936-086X (Electronic) IS - 1936-0851 (Print) IS - 1936-0851 (Linking) VI - 8 IP - 10 DP - 2014 Oct 28 TI - Bromelain surface modification increases the diffusion of silica nanoparticles in the tumor extracellular matrix. PG - 9874-83 LID - 10.1021/nn502807n [doi] AB - 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. FAU - Parodi, Alessandro AU - Parodi A AD - Department of Nanomedicine, Houston Methodist Research Institute , Houston, Texas 77030, United States. FAU - Haddix, Seth G AU - Haddix SG FAU - Taghipour, Nima AU - Taghipour N FAU - Scaria, Shilpa AU - Scaria S FAU - Taraballi, Francesca AU - Taraballi F FAU - Cevenini, Armando AU - Cevenini A FAU - Yazdi, Iman K AU - Yazdi IK FAU - Corbo, Claudia AU - Corbo C FAU - Palomba, Roberto AU - Palomba R FAU - Khaled, Sm Z AU - Khaled SZ FAU - Martinez, Jonathan O AU - Martinez JO FAU - Brown, Brandon S AU - Brown BS FAU - Isenhart, Lucas AU - Isenhart L FAU - Tasciotti, Ennio AU - Tasciotti E LA - eng GR - F31 CA154119/CA/NCI NIH HHS/United States GR - R21 CA173579/CA/NCI NIH HHS/United States GR - 1R21CA173579-01A1/CA/NCI NIH HHS/United States GR - 1F31CA154119/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20140917 PL - United States TA - ACS Nano JT - ACS nano JID - 101313589 RN - 7631-86-9 (Silicon Dioxide) RN - 9001-00-7 (Bromelains) SB - IM MH - Bromelains/*chemistry MH - Diffusion MH - Extracellular Matrix/*chemistry MH - Microscopy, Electron, Transmission MH - *Nanoparticles MH - Neoplasms/blood supply/*chemistry/pathology MH - Silicon Dioxide/*chemistry MH - Spectroscopy, Fourier Transform Infrared MH - Surface Properties PMC - PMC4212787 OTO - NOTNLM OT - Bromelain OT - cancer OT - cellular uptake OT - extracellular matrix digestion OT - mesoporous silica nanoparticle modification EDAT- 2014/08/15 06:00 MHDA- 2015/10/01 06:00 PMCR- 2015/08/13 CRDT- 2014/08/15 06:00 PHST- 2014/08/15 06:00 [entrez] PHST- 2014/08/15 06:00 [pubmed] PHST- 2015/10/01 06:00 [medline] PHST- 2015/08/13 00:00 [pmc-release] AID - 10.1021/nn502807n [doi] PST - ppublish SO - ACS Nano. 2014 Oct 28;8(10):9874-83. doi: 10.1021/nn502807n. Epub 2014 Sep 17.