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Abstract:
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Hepatocellular carcinoma (HCC ) is the third most common cause of cancer -related deaths worldwide , accounting for over 600 ,000 deaths per year . The most common treatment strategy for intermediate and advanced stage unresectable HCC is transarterial chemoembolization (TACE ) , which involves the local administration of a chemotherapeutic drug combined with arterial occlusion resulting in ischemic tumor necrosis . However , TACE suffers from inadvertent exposure of noncancerous liver parenchyma to embolic agents resulting in liver injury . In some cases , over -embolization has lead to infection , necrosis of unaffected liver tissue , and even liver failure which suggests the need for a biocompatible , multifunctional embolic material which can deliver anticancer drugs with high target specificity . Our laboratory has recently developed a method to fabricate porous silicon (pSi ) microparticles with defined physicochemical properties based on photolithography and anodic etching . These microparticles function as multistage drug delivery systems that can circumvent the biobarriers present in the systemic circulation enabling site -specific localization and release of chemotherapy and imaging agents . The versatility of the fabrication process enables the realization of microparticles ranging in size from 600nm to 116[mu]m in diameter with varying shapes , including discoidal , cylindrical and hemispherical , and varying porosity with pore sizes ranging from 6nm to greater than 50nm in diameter . Nanoparticles , such as quantum dots , siRNA -loaded nanoliposomes , gadolinium -based contrast agents , gold and iron oxide nanoparticles , are loaded in pSi microparticles by tailoring their pore sizes and surface chemistries . This thesis presents preliminary results on the applicability of biocompatible , engineered pSi microparticles as an embolic agent for HCC chemoembolization therapy . Hemispherical microparticles with 116[mu]m diameter were successfully fabricated and suspended in phosphate buffered saline (PBS ) . A microvascular construct was rapid prototyped in polydimethylsiloxane (PDMS ) as an in vitro experimental platform to study the embolization behavior of pSi microparticles . Oxidized pSi microparticles were introduced into the microfluidic device at an appropriate flow rate and time -lapse images were taken showing the formation of occlusions at the bifurcation within minutes of administration . Furthermore , penetration through the bifurcation was completely hindered suggesting that pSi microparticles can potentially be used as a biocompatible , multifunctional chemoembolization agent . Although these results are promising , further investigations are warranted . |