Keratin-Based Nanoparticles with Tumor-Targeting and Cascade Catalytic Capabilities for the Combinational Oxidation Phototherapy of Breast Cancer
Journal
ACS Applied Materials and Interfaces
Journal Volume
13
Journal Issue
32
Pages
38074-38089
Date Issued
2021
Author(s)
Abstract
Photodynamic therapy (PDT) holds tantalizing prospects of a prominent cancer treatment strategy. However, its efficacy remains limited by virtue of the hypoxic tumor microenvironment and the inadequate tumor-targeted delivery of photosensitizers, and these can be further exacerbated by the lack of development of a well-controlled nitric oxide (NO) release system at the target site. Inspired by Chinese medicine, we propose a revealing new keratin application. Keratin has garnered attention as an NO generator; however, its oncological use has rarely been investigated. We hypothesized that the incorporation of a phenylboronic acid (PBA) targeting ligand/methylene blue (MB) photosensitizer with a keratin NO donor would facilitate precise tumor delivery, enhancing PDT. Herein, we demonstrated that MB@keratin/PBA/d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) nanoparticles (MB@KPTNPs) specifically targeted breast cancer cells and effectively suppressed their growth. Through MB-mediated biometabolism, the endocytic MB@KPTNPs produced a sufficient amount of intracellular NO that reduced the glutathione level while boosting the efficiency of PDT. A therapeutic combination of NO/PDT was therefore achieved, resulting in significant inhibition of both in vivo tumor growth and lung metastasis. These findings underscore the importance of utilizing keratin-based nanoparticles that simultaneously combine targeting of the tumor and self-generating NO with a cascading catalytic ability as a novel oxidation therapeutic strategy for enhancing PDT. ? 2021 American Chemical Society.
Subjects
biomass human hair keratin
glutathione depletion
nitric oxide generation
photodynamic therapy
reactive nitrogen species
tumor targeting
Catalytic oxidation
Diseases
Nanoparticles
Nitric oxide
Photodynamic therapy
Photosensitizers
Tumors
Breast cancer cells
Catalytic capability
Phenylboronic acids
Photodynamic therapy (PDT)
Targeting ligands
Therapeutic strategy
Tumor microenvironment
Tumor targeted delivery
Keratin
antineoplastic agent
keratin
nanoparticle
nitric oxide
animal
Bagg albino mouse
breast tumor
female
human
mouse
photochemotherapy
procedures
tumor cell line
Animals
Antineoplastic Agents
Breast Neoplasms
Cell Line, Tumor
Female
Humans
Keratins
Mice
Mice, Inbred BALB C
Nitric Oxide
Photochemotherapy
SDGs
Type
journal article