Publications

Bladder cancer treatment via intravesical drug administration achieves reasonable survival rates but suffers from low therapeutic efficacy. To address the latter, self-propelled nanoparticles or nanobots have been proposed, taking advantage of their enhanced diffusion and mixing capabilities in urine when compared with conventional drugs or passive nanoparticles. However, the translational capabilities of nanobots in treating bladder cancer are underexplored. Here, we tested radiolabelled mesoporous silica-based urease-powered nanobots in an orthotopic mouse model of bladder cancer. In vivo and ex vivo results demonstrated enhanced nanobot accumulation at the tumour site, with an eightfold increase revealed by positron emission tomography in vivo. Label-free optical contrast based on polarization-dependent scattered light-sheet microscopy of cleared bladders confirmed tumour penetration by nanobots ex vivo. Treating tumour-bearing mice with intravesically administered radio-iodinated nanobots for radionuclide therapy resulted in a tumour size reduction of about 90%, positioning nanobots as efficient delivery nanosystems for bladder cancer therapy.© 2024. The Author(s).

JTD Keywords: cell, drug-delivery, nanomotors, tissue, Bladder cancers, Cancer therapy, Diseases, Drug administration, Drug delivery, Enhanced diffusion, Enhanced mixing, Ex-vivo, In-vivo, Mammals, Nanobots, Nanoparticles, Nanosystems, Oncology, Positron emission tomography, Radioisotopes, Silica, Survival rate, Therapeutic efficacy, Tumor penetration, Tumors

MicroRNAs (miRNAs) are small non-coding endogenous RNAs, which are attracting a growing interest as therapeutic molecules due to their central role in major diseases. However, the transformation of these biomolecules into drugs is limited due to their unstability in the bloodstream, caused by nucleases abundantly present in the blood, and poor capacity to enter cells. The conjugation of miRNAs to nanoparticles (NPs) could be an effective strategy for their clinical delivery. Herein, the engineering of non-liposomal lipid nanovesicles, named quatsomes (QS), for the delivery of miRNAs and other small RNAs into the cytosol of tumor cells, triggering a tumor-suppressive response is reported. The engineered pH-sensitive nanovesicles have controlled structure (unilamellar), size (<150 nm) and composition. These nanovesicles are colloidal stable (>24 weeks), and are prepared by a green, GMP compliant, and scalable one-step procedure, which are all unavoidable requirements for the arrival to the clinical practice of NP based miRNA therapeutics. Furthermore, QS protect miRNAs from RNAses and when injected intravenously, deliver them into liver, lung, and neuroblastoma xenografts tumors. These stable nanovesicles with tunable pH sensitiveness constitute an attractive platform for the efficient delivery of miRNAs and other small RNAs with therapeutic activity and their exploitation in the clinics.

JTD Keywords: cancer therapy, mirnas delivery, nanocarriers, nanovesicles, neuroblastoma, pediatric cancer, quatsomes, Biodistribution, Cancer therapy, Cell engineering, Cells, Cholesterol, Controlled drug delivery, Diseases, Dna, Dysregulated ph, Lipoplex, Microrna delivery, Mirnas delivery, Nanocarriers, Nanoparticles, Nanovesicle, Nanovesicles, Neuroblastoma, Neuroblastomas, Pediatric cancer, Ph sensitive, Ph sensors, Quatsome, Quatsomes, Rna, Sirna, Sirna delivery, Sirnas delivery, Small interfering rna, Small rna, Targeted drug delivery, Tumors, Vesicles