A high-throughput microparticle microarray platform for dendritic cell-targeting vaccines

Acharya, Abhinav P.; Clare‐Salzler, Michael; Keselowsky, Benjamin G.

doi:10.1016/j.biomaterials.2009.04.032

Cited by 53 publications

(48 citation statements)

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“…Fabrication (Fig. 1A) was based on a modification of our earlier cell array (32) and provided cell attachment to drug-loaded polymer islands surrounded by nonfouling surface treatment (Fig. 1B).…”

Section: Resultsmentioning

confidence: 99%

“…No differences in apoptosis were noted between the configurations at different drug loading amounts, indicating Glass coverslips are robotically printed with amine-terminated silane in isolated spots and then coated with titanium and gold. Processing exposes silane-grafted islands, whereas the gold region is passivated by the addition of a nonfouling PEG background (32). Drug-loaded EVA is then printed over the exposed silane islands, and amine groups promote polymer adhesion.…”

Section: -H)mentioning

confidence: 99%

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Drug-eluting microarrays to identify effective chemotherapeutic combinations targeting patient-derived cancer stem cells

Carstens

Fisher

Acharya

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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A new paradigm in oncology establishes a spectrum of tumorigenic potential across the heterogeneous phenotypes within a tumor. The cancer stem cell hypothesis postulates that a minute fraction of cells within a tumor, termed cancer stem cells (CSCs), have a tumor-initiating capacity that propels tumor growth. An application of this discovery is to target this critical cell population using chemotherapy; however, the process of isolating these cells is arduous, and the rarity of CSCs makes it difficult to test potential drug candidates in a robust fashion, particularly for individual patients. To address the challenge of screening drug libraries on patient-derived populations of rare cells, such as CSCs, we have developed a drug-eluting microarray, a miniaturized platform onto which a minimal quantity of cells can adhere and be exposed to unique treatment conditions. Hundreds of drug-loaded polymer islands acting as drug depots colocalized with adherent cells are surrounded by a nonfouling background, creating isolated culture environments on a solid substrate. Significant results can be obtained by testing <6% of the cells required for a typical 96-well plate. Reliability was demonstrated by an average coefficient of variation of 14% between all of the microarrays and 13% between identical conditions within a single microarray. Using the drug-eluting array, colorectal CSCs isolated from two patients exhibited unique responses to drug combinations when cultured on the drug-eluting microarray, highlighting the potential as a prognostic tool to identify personalized chemotherapeutic regimens targeting CSCs.personalized medicine | chemopredictive | cancer stem cell | microarray | combination therapy

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Section: Resultsmentioning

confidence: 99%

Section: -H)mentioning

confidence: 99%

Drug-eluting microarrays to identify effective chemotherapeutic combinations targeting patient-derived cancer stem cells

Carstens

Fisher

Acharya

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…As said before (see 'Matrix protein interaction with synthetics surfaces') after implantation of the biomaterial, some ECM proteins spontaneously adsorb onto synthetic biomaterials (Anderson, et al, 2008;Chang et al, 2009) and can modulate leukocyte adhesion and inflammatory responses to implants (Anderson et al, 2008;Hunter et al, 1999;Jenney & Anderson, 2000;Keselowsky et al, 2007;Shen & Horbett, 2001;Tang & Eaton, 1993). The adaptive immune response to the new biomaterial can be altered by these inflammatory responses (Acharya et al, 2009;Acharya et al, 2008).…”

Section: Immunological Cell-protein-materials Interactionsmentioning

confidence: 99%

“…It has been shown that DCs interactions with various biomaterials modulate DCs functions (Babensee, 2008;Jones, 2008) and that DCs express multiple integrins (Ammon et al, 2000;Brown et al, 1997;Dalgaard et al, 2005;Dubey et al, 1995;Hamakawa et al, 2006;Lu et al, 1995;Sung et al, 2006), but there are surprisingly few investigations into the effects of integrin binding to ECM proteins on DCs maturation and only a few investigations have begun to elucidate the mechanisms involved into the modulation of DC functions (Acharya et al, 2009;Acharya et al, 2008;Acharya et al, 2011;Brand et al, 1998;Kohl et al, 2007;Shankar et al, 2010). DCs have been cultured on surfaces presenting a uniform gradient of the integrin targeting RGD peptide and demonstrate the utility of the surface density gradient platform as a high-throughput method to investigate RGD densitydependent DCs adhesive responses (Acharya et al, 2010).…”

Section: Dendritic Cells and Biomaterials Interactionmentioning

confidence: 99%

“…Using biomaterials has been demonstrated to modulate DCs functions (Babensee, 2008;Reddy et al, 2006). Specific proteins adsorbed onto biomaterials can induce different inflammatory responses and can alter the adaptive immune response (Acharya et al, 2009;Acharya et al, 2008). In vivo, upon implantation, numerous proteins are quickly adsorbed on the implant, including ECM proteins.…”

Section: Modulation Of Adaptive Immune Response Introductionmentioning

confidence: 99%

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