Biodegradable, pH-Sensitive Hollow Mesoporous Organosilica Nanoparticle (HMON) with Controlled Release of Pirfenidone and Ultrasound-Target-Microbubble-Destruction (UTMD) for Pancreatic Cancer Treatment

The dense extracellular matrix (ECM) and hypovascular networks were often found in solid pancreatic tumors form an impenetrable barrier, leading to limited uptake of chemotherapeutics and thus undesirable treatment outcomes.Methods: A biodegradable nanoplatform based on hollow mesoporous organosilica nanoparticle (HMON) was designed as an effective delivery system for pirfenidone (PFD) to overcome the challenges in pancreatic tumor treatment. By varying pH producing a mildly acidic environment to emulate tumor cells, results in cleavage of the acetal bond between HMON nanoparticle and gating molecular, gemcitabine (Gem), enabling its controlled release.Results: The in vitro and in vivo immunocytochemistry evaluations demonstrated an excellent ECM regulation efficacy of the nanoplatform and therefore the improved penetration of drug into the cells. The technique employed was especially enhanced when mediated with ultrasound target microbubble destruction (UTMD). Evaluations culminated with pancreatic cancer bearing mice and demonstrated therapeutic efficacy, good biodegradability, and negligible systemic toxicity.Conclusion: the designed Gem gated biodegradable nanosystem is expected to provide an alternative way of improving antitumor efficacy by down-regulation of ECM levels and offers a passive-targeted therapy for pancreatic cancer treatment.

致密的细胞外基质（ECM）和低血管网络常见于实体胰腺肿瘤中，形成了一道难以穿透的屏障，导致化疗药物摄取有限，进而治疗效果不佳。 方法：设计了一种基于中空介孔有机硅纳米粒子（HMON）的可生物降解纳米平台，作为吡非尼酮（PFD）的有效递送系统，以克服胰腺肿瘤治疗中的挑战。通过改变pH值产生微酸性环境来模拟肿瘤细胞，导致HMON纳米粒子与门控分子吉西他滨（Gem）之间的缩醛键断裂，从而实现其控释。 结果：体外和体内免疫细胞化学评估表明，该纳米平台具有出色的ECM调节功效，从而提高了药物对细胞的穿透性。当采用超声靶向微泡破坏（UTMD）介导时，该技术效果尤为增强。对荷胰腺癌小鼠的评估最终证明了其治疗效果、良好的生物降解性以及可忽略的全身毒性。 结论：所设计的吉西他滨门控可生物降解纳米系统有望通过下调ECM水平提供一种提高抗肿瘤疗效的替代方法，并为胰腺癌治疗提供一种被动靶向疗法。