| Title: |
A photoactivable multi-inhibitor nanoliposome for tumour control and simultaneous inhibition of treatment escape pathways |
| Authors: |
Spring, Bryan Q; Bryan Sears, R; Zheng, Lei Zak; Mai, Zhiming; Watanabe, Reika; Sherwood, Margaret E; Schoenfeld, David A; Pogue, Brian W; Pereira, Stephen P; Villa, Elizabeth; Hasan, Tayyaba |
| Source: |
Nature Nanotechnology, vol 11, iss 4 |
| Publisher Information: |
eScholarship, University of California |
| Publication Year: |
2016 |
| Collection: |
University of California: eScholarship |
| Subject Terms: |
3206 Medical Biotechnology (for-2020); 32 Biomedical and Clinical Sciences (for-2020); 3211 Oncology and Carcinogenesis (for-2020); Orphan Drug (rcdc); Rare Diseases (rcdc); Nanotechnology (rcdc); Cancer (rcdc); Bioengineering (rcdc); 5.1 Pharmaceuticals (hrcs-rac); Cancer (hrcs-hc); Anilides (mesh); Animals (mesh); Antineoplastic Agents (mesh); Cell Line; Tumor (mesh); Humans (mesh); Liposomes (mesh); Male (mesh); Mice (mesh); Photosensitizing Agents (mesh); Porphyrins (mesh); Pyridines (mesh); Xenograft Model Antitumor Assays (mesh); Nanoscience & Nanotechnology (science-metrix) |
| Subject Geographic: |
378 - 387 |
| Description: |
Nanoscale drug delivery vehicles can facilitate multimodal therapies of cancer by promoting tumour-selective drug release. However, few are effective because cancer cells develop ways to resist and evade treatment. Here, we introduce a photoactivable multi-inhibitor nanoliposome (PMIL) that imparts light-induced cytotoxicity in synchrony with a photoinitiated and sustained release of inhibitors that suppress tumour regrowth and treatment escape signalling pathways. The PMIL consists of a nanoliposome doped with a photoactivable chromophore (benzoporphyrin derivative, BPD) in the lipid bilayer, and a nanoparticle containing cabozantinib (XL184)—a multikinase inhibitor—encapsulated inside. Near-infrared tumour irradiation, following intravenous PMIL administration, triggers photodynamic damage of tumour cells and microvessels, and simultaneously initiates release of XL184 inside the tumour. A single PMIL treatment achieves prolonged tumour reduction in two mouse models and suppresses metastatic escape in an orthotopic pancreatic tumour model. The PMIL offers new prospects for cancer therapy by enabling spatiotemporal control of drug release while reducing systemic drug exposure and associated toxicities. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
unknown |
| Relation: |
qt4ft402cx; https://escholarship.org/uc/item/4ft402cx; https://escholarship.org/content/qt4ft402cx/qt4ft402cx.pdf |
| DOI: |
10.1038/nnano.2015.311 |
| Availability: |
https://escholarship.org/uc/item/4ft402cx; https://escholarship.org/content/qt4ft402cx/qt4ft402cx.pdf; https://doi.org/10.1038/nnano.2015.311 |
| Rights: |
public |
| Accession Number: |
edsbas.C8CF1B1F |
| Database: |
BASE |