Red‐Light‐Controlled Release of Drug–Ru Complex Conjugates from Metallopolymer Micelles for Phototherapy in Hypoxic Tumor Environments

Abstract

Traditional photodynamic phototherapy is not efficient for anticancer treatment because solid tumors have a hypoxic microenvironment. The development of photoactivated chemotherapy based on photoresponsive polymers that can be activated by light in the "therapeutic window" would enable new approaches for basic research and allow for anticancer phototherapy in hypoxic conditions. This work synthesizes a novel Ru-containing block copolymer for photoactivated chemotherapy in hypoxic tumor environment. The polymer has a hydrophilic poly(ethylene glycol) block and a hydrophobic Ru-containing block, which contains red-light-cleavable (650-680 nm) drug-Ru complex conjugates. The block copolymer self-assembles into micelles, which can be efficiently taken up by cancer cells. Red light induces release of the drug-Ru complex conjugates from the micelles and this process is oxygen independent. The released conjugates inhibit tumor cell growth even in hypoxic tumor environment. Furthermore, the Ru-containing polymer for photoactivated chemotherapy in a tumor-bearing mouse model is applied. Photoactivated chemotherapy of the polymer micelles demonstrates efficient tumor growth inhibition. In addition, the polymer micelles do not cause any toxic side effects to mice during the treatment, demonstrating good biocompatibility of the system to the blood and healthy tissues. The novel red-light-responsive Ru-containing polymer provides a new platform for phototherapy against hypoxic tumors.

Hypoxia-activated NIR photosensitizer anchoring in the mitochondria for photodynamic therapy

“…The hypoxic environment is an important feature of tumours due to the insufficient supply of oxygen. Several methods have been reported for hypoxic tumour therapy, such as those based on thermoresponsive nanoplatforms, 24 decomposition of the endogenous H 2 O 2 system, 25,26 electron transfer mediated upconversion nanoparticles (UCNPs), 27 light-controlled drug release complex conjugates 28 and so on. Nitroreductase (NTR) is a well-known specic enzyme overexpressed in solid tumours due to the hypoxic microenvironment which can effectively reduce the nitroaromatic to the corresponding arylamine by using reduced nicotinamide adenine dinucleotide (NADH) as an electron donor.…”

Visible Light‐Responsive Dynamic Biomaterials: Going Deeper and Triggering More

“…[ 100 ] Recent work on ruthenium polypyridyl‐containing micelles demonstrated their use in vivo as well. [ 101–103 ] Upon degradation, the micelles released ruthenium photoproducts into local tissue and the bloodstream; no ruthenium buildup in any major organ (i.e., liver, spleen, kidney, lung) or tissue damage was observed.…”

Boron Dipyrromethene Nano‐Photosensitizers for Anticancer Phototherapies

“…In PDT, PSs with sensitivity to red or near‐infrared (NIR) light in the “650–900 nm” therapeutic window have received increasing attention because they allow deeper tissue penetration than those with sensitivity to ultraviolet (UV) or short‐wavelength visible (VIS) light . PSs with long triplet lifetimes are also desired to ensure high ROS production yields.…”

“…PDT is based on the electron or energy interactions between PSs in triplet states and oxygen (O 2 ) or nearby substrates under light irradiation, generating ROS, such as free radicals (type I) and singlet oxygen ( 1 O 2 ) (type II) . When certain PSs specifically localize in tumor sites via systemic administration and are then activated by light with a specific wavelength, a series of photochemical reactions are initiated and generate ROS to inhibit tumor growth …”