Surface-fill hydrogel attenuates the oncogenic signature of complex anatomical surface cancer in a single application

Abstract

Tumors growing in a sheet-like manner on the surface of organs and tissues with complex topologies represent a difficult-to-treat clinical scenario. Their complete surgical resection is difficult due to the complicated anatomy of the diseased tissue. Residual cancer often responds poorly to systemic therapy and locoregional treatment is hindered by the limited accessibility to microscopic tumor foci. Here we engineered a peptide-based surface-fill hydrogel (SFH) that can be syringe- or spray-delivered to surface cancers during surgery or used as a primary therapy. Once applied, SFH can shape change in response to alterations in tissue morphology that may occur during surgery. Implanted SFH releases nanoparticles composed of miRNA and intrinsically disordered peptides that enter cancer cells attenuating their oncogenic signature. With a single application, SFH shows efficacy in four preclinical models of mesothelioma demonstrating a therapeutic impact of local application of tumor-specific miRNA, which might change the treatment paradigm for mesothelioma and possibly other surface cancers.

Tissue architecture in tumor initiation and progression

“…Sheet-like lesions are difficult to efficiently resect surgically. The use of topical hydrogels containing nanoparticles with small RNAs is agnostic to tissue topography and can be used to treat sheet-like lesions [87]. Therapeutic efficiency is further influenced by tumor composition and morphology, as well as by their underlying physical properties.…”

Osteogenic peptides in periodontal ligament stem cell-containing three-dimensional bioscaffolds promote bone healing

“…The inclusion of hydrophobic domains, charge interactions, or hydrogen bonds between the hydrogel and factors can slow the release. 46,47 We will further optimize the delivery of SDSSD in the follow-up studies.…”

Current State of Pleural-Directed Adjuncts Against Malignant Pleural Mesothelioma

“…Recently, a new materials platform harnessing the compelling therapeutic traits of microRNA ( 39 ) (miRNA or miR) that can resolve some of the limitations of MPM intracavitary therapies has been described. A novel biodegradable thin-film depot and delivery material consisting of nanoparticles, prepared by complexing amphiphilic cationic peptides (first polymer) with negatively charged miRNA, which are then embedded into a shear-thinning, self-assembling peptide (second polymer) hydrogel, exerted preferential anti-cancer effects in several murine MPM xenografts ( 40 ). This peptide-based surface-fill hydrogel (SFH) nanocomposite can be applied directly to a body cavity via percutaneous or surgical access by syringe injection or sprayed to coat anatomic surfaces.…”

“…Furthermore, the efficacy of SFH with encapsulated miR-215 ( 42 ) or miR-206 ( 43 ) nanoparticles in a single administration were evaluated in pre-clinical models of MPM. Tumor resection sites receiving adjuvant SFH miR-215 or miR-206 therapy showed minimal tumor recurrence compared to resection controls without miRNA treatment ( 40 ).…”