Enhanced Uptake of Porous Silica Microparticles by Bifunctional Surface Modification with a Targeting Antibody and a Biocompatible Polymer

Cheng, Kai; Blumen, Steven R.; MacPherson, Maximilian B.; Steinbacher, Jeremy L.; Mossman, Brooke T.; Landry, Christopher C.

doi:10.1021/am100530t

Cited by 39 publications

(26 citation statements)

References 48 publications

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“…Moreover, the external surface of MSNs can easily be functionalized with target biomolecules, i.e. proteins/antibodies [27][28][29], peptides [30,31] or saccharides [32][33][34], that can be recognized by receptors overexpressed by tumor cells [35][36][37]. Alternatively, these macromolecules can modify their conformation, as a response to a change of environmental conditions (i.e.…”

Section: Introductionmentioning

confidence: 99%

Interactions between bovine serum albumin and mesoporous silica nanoparticles functionalized with biopolymers

Nairi

Medda

Piludu

et al. 2018

Chemical Engineering Journal

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Biomedical application of nanoparticles is largely associated to their fate in biological media which, in turn, is related to their surface properties. Surface functionalization plays a key role in determining biodegradation, cytotoxicity and biodistribution through interactions which may be mediated by the macromolecules occurring in biological media. A typical example is given by several proteins which lead to the formation of coated nanoparticles referred as protein corona. In this work we focus on mesoporous silica nanoparticles which, due to their intrinsic textural features, show potential as carriers for sustained drug release. Mesoporous silica nanoparticles functionalized by different biopolymers such as hyaluronic acid and chitosan were synthesized and characterized through small angle X-rays scattering, thermal analysis, and infrared spectroscopy. Biopolymer-coated mesoporous silica nanoparticles were used to investigate the interaction with bovine serum albumin, and to point out the role of different biopolymer coating. Gold-conjugated-bovine serum albumin was used to gain evidence on the occurrence of surface bound proteins enabling direct observation by transmission electron microscopy. Our findings provide insights on how different biopolymers affect the formation of a protein corona around functionalized mesoporous silica nanoparticles.

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Section: Introductionmentioning

confidence: 99%

Interactions between bovine serum albumin and mesoporous silica nanoparticles functionalized with biopolymers

Nairi

Medda

Piludu

et al. 2018

Chemical Engineering Journal

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“…APMS particle diameter and pore size are easily tunable for optimal delivery of specific agents (Gallis and Landry 2002;Nassivera et al 2002). As previously published, these characteristics make APMS an ideal vehicle for carrying chemotherapeutic agents, DNA plasmids, small interfering RNA (siRNA), or other macromolecules (Blumen et al 2007;Cheng et al 2010). Most important, amorphous silicas produce no chronic adverse biological responses in contrast to crystalline silicas, presumably because of their lack of crystalline structure and increased solubility over time (Warheit 2001).…”

mentioning

confidence: 98%

A Multifunctional Mesothelin Antibody-tagged Microparticle Targets Human Mesotheliomas

Macura

Hillegass

Steinbacher

et al. 2012

J Histochem Cytochem.

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Pleural and peritoneal mesotheliomas (MMs) are chemoresistant tumors with no effective therapeutic strategies. The authors first injected multifunctional, acid-prepared mesoporous spheres (APMS), microparticles functionalized with tetraethylene glycol oligomers, intraperitoneally into rodents. Biodistribution of APMS was observed in major organs, peritoneal lavage fluid (PLF), and urine of normal mice and rats. After verification of increased mesothelin in human mesotheliomas injected into severe combined immunodeficient (SCID) mice, APMS were then functionalized with an antibody to mesothelin (APMS-MB) or bovine serum albumin (BSA), a nonspecific protein control, and tumor targeting was evaluated by inductively coupled plasma mass spectrometry and multifluorescence confocal microscopy. Some APMS were initially cleared via the urine over a 24 hr period, and small amounts were observed in liver, spleen, and kidneys at 24 hr and 6 days. Targeting with APMS-MB increased APMS uptake in mesenteric tumors at 6 days. Approximately 10% to 12% of the initially injected amount was observed in both spheroid and mesenteric MM at this time point. The data suggest that localized delivery of APMS-MB into the peritoneal cavity after encapsulation of drugs, DNA, or macromolecules is a novel therapeutic approach for MM and other tumors (ovarian and pancreatic) that overexpress mesothelin.

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“…APMS microparticles were modified using an antibody to mesothelin (MB) and loaded with DOX as previously described [13,24]. …”

Section: Methodsmentioning

confidence: 99%

Microspheres targeted with a mesothelin antibody and loaded with doxorubicin reduce tumor volume of human mesotheliomas in xenografts

et al. 2013

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BackgroundMalignant mesotheliomas (MMs) are chemoresistant tumors related to exposure to asbestos fibers. The long latency period of MM (30-40 yrs) and heterogeneity of tumor presentation make MM difficult to diagnose and treat at early stages. Currently approved second-line treatments following surgical resection of MMs include a combination of cisplatin or carboplatin (delivered systemically) and pemetrexed, a folate inhibitor, with or without subsequent radiation. The systemic toxicities of these treatments emphasize the need for more effective, localized treatment regimens.MethodsAcid-prepared mesoporous silica (APMS) microparticles were loaded with doxorubicin (DOX) and modified externally with a mesothelin (MB) specific antibody before repeated intraperitoneal (IP) injections into a mouse xenograft model of human peritoneal MM. The health/weight of mice, tumor volume/weight, tumor necrosis and cell proliferation were evaluated in tumor-bearing mice receiving saline, DOX high (0.2 mg/kg), DOX low (0.05 mg/kg), APMS-MB, or APMS-MB-DOX (0.05 mg/kg) in saline.ResultsTargeted therapy (APMS-MB-DOX at 0.05 mg/kg) was more effective than DOX low (0.05 mg/kg) and less toxic than treatment with DOX high (0.2 mg/kg). It also resulted in the reduction of tumor volume without loss of animal health and weight, and significantly decreased tumor cell proliferation. High pressure liquid chromatography (HPLC) of tumor tissue confirmed that APMS-MB-DOX particles delivered DOX to target tissue.ConclusionsData suggest that targeted therapy results in greater chemotherapeutic efficacy with fewer adverse side effects than administration of DOX alone. Targeted microparticles are an attractive option for localized drug delivery.

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Enhanced Uptake of Porous Silica Microparticles by Bifunctional Surface Modification with a Targeting Antibody and a Biocompatible Polymer

Cited by 39 publications

References 48 publications

Interactions between bovine serum albumin and mesoporous silica nanoparticles functionalized with biopolymers

Interactions between bovine serum albumin and mesoporous silica nanoparticles functionalized with biopolymers

A Multifunctional Mesothelin Antibody-tagged Microparticle Targets Human Mesotheliomas

Microspheres targeted with a mesothelin antibody and loaded with doxorubicin reduce tumor volume of human mesotheliomas in xenografts

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