Size-Switchable Nanoparticles with Self-Destructive and Tumor Penetration Characteristics for Site-Specific Phototherapy of Cancer

Abstract

The normoxic and hypoxic microenvironments in solid tumors cause cancer cells to show different sensitivities to various treatments. Therefore, it is essential to develop different therapeutic modalities based on the tumor microenvironment. In this study, we designed size-switchable nanoparticles with self-destruction and tumor penetration characteristics for site-specific phototherapy of cancer. This was achieved by photodynamic therapy in the perivascular normoxic microenvironment due to high local oxygen concentrations and photothermal therapy (PTT) in the hypoxic microenvironment, which are not in proximity to blood vessels due to a lack of effective approaches for heat transfer. In brief, a poly­(amidoamine) dendrimer with photothermal agent indocyanine green (PAMAM-ICG) was conjugated to the amphiphilic polymer through a singlet oxygen-responsive thioketal linker and then loaded with photosensitizer chlorin e6 (Ce6) to construct a nanotherapy platform (denoted as SNPICG/Ce6). After intravenous injection, SNPICG/Ce6 was accumulated at the perivascular sites of the tumor. The singlet oxygen produced by Ce6 can ablate the tumor cells in the normoxic microenvironment and simultaneously cleave the thioketal linker, allowing the release of small PAMAM-ICGs with improved tumor penetration for PTT in the hypoxic microenvironment. This tailored site-specific phototherapy in normoxic and hypoxic microenvironments provides an effective strategy for cancer therapy.

Surface-bound reactive oxygen species generating nanozymes for selective antibacterial action

“…Moreover, a lipid bilayer is permeable to O 2 but impermeable to AA 35 or SOSG 36 . In addition, using Chlorin e6 (Ce6)-preloaded PLGA (poly(lactic-co-glycolic acid)) nanoparticle (i.e., Ce6/PLGA) as a model for free 1 O 2 -generating nanoparticles (Ce6 is an organic photosensitizer that generates free 1 O 2 upon near-infrared light irradiation (λ~660 nm) 37,38 ), we observed that coating Ce6/PLGA with a lipid bilayer (composed of DOPC: DSPE-PEG = 0.90: 0.10) (Fig. 1f, g) that is 11 nm in thickness (Supplementary Fig.…”

Nanodrug Delivery Systems Modulate Tumor Vessels to Increase the Enhanced Permeability and Retention Effect

“…However, due to the existence of various barriers, they often have difficulty in reaching the core of the tumor. Therefore, nanodrugs of variable size can be used to simultaneously achieve long-time circulation, good passive targeting, and high permeability [178][179][180][181][182][183].…”

Self‐Assembled Ag2S‐QD Vesicles for In Situ Responsive NIR‐II Fluorescence Imaging‐Guided Photothermal Cancer Therapy

“…High penetration into biological tissues of nanoprobes is a prerequisite for cancer therapy. [ 17 ] We further tested the penetration ability of fluorescein isothiocyanate (FITC)‐labeled Ag 2 S Ve by using MCF‐7 multicellular spheroids (MCSs). Ag 2 S QDs and two kinds of Ag 2 S Ve were incubated respectively with MCSs for 6 h and monitored by confocal laser scanning microscope (CLSM).…”