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

Abstract

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.

Nanoparticle-Based Drug Delivery in Cancer Therapy and Its Role in Overcoming Drug Resistance

“…Mesoporous silica nanoparticle carriers are a type of SNPs which are suitable for drug delivery ( Almeida et al, 2014 ; Gao et al, 2019 ). The large internal pore volume enables them to encapsulate the maximum amount of anticancer drugs, and the supramolecular components act as a cap, allowing capture and release of drugs ( Cheng et al, 2019 ; Lei et al, 2019 ).…”

Dissolving Microneedles with Spatiotemporally controlled pulsatile release Nanosystem for Synergistic Chemo-photothermal Therapy of Melanoma

“…Traditional chemotherapy shows unsatisfactory efficacy in malignant melanoma and toxic side effects usually lead to poor quality of life 4 . Another option proposed for the treatment of melanoma was of external microenergy, including ultrasound therapy 5 - 7 , magnetic response therapy 8 , 9 , and photothermal therapy (PTT) 10 - 12 . PTT can induce thermal ablation of tumor cells by converting light energy to heat using photothermal agents, causing irreversible damage to tumors but no damage to normal tissues.…”

Induction and characterization of pancreatic cancer in a transgenic pig model

“…Due to the lack of a suitable large animal model of pancreatic cancer, many new locoregional therapies for pancreatic cancer are initially tested in normal pig pancreas [9,11], or in nude mice with subcutaneous [6] or orthotopic [15] pancreatic tumor xenografts. Normal pancreas is not an ideal model for pancreatic cancer.…”

“…Several new locoregional therapies for pancreatic cancer have been proposed, including local drug delivery using ultrasound microbubbles [ 6 , 7 ], pancreatic transarterial chemoinfusion [ 8 – 11 ], pancreatic chemoembolization using lipiodol [ 12 ] or drug-eluting beads [ 13 ], intratumoral injection of oncolytic virus [ 14 ], and peritumoral injection of siRNA [ 15 ]. Translation to human trials has been challenging.…”