Development of red-light cleavable PEG-PLA nanoparticles as delivery systems for cancer therapy.

The development of targeted delivery systems can improve the selectivity of cancer drugs. Additionally, a system that promotes the controlled delivery of the drug triggered by an external stimulus in the exact target tissue is highly desirable. Regarding the light stimulus, the NIR window (650-950 nm) is the most suitable due to its higher capacity of penetration in human tissues and less harmful effects on normal cells. In this work, new red-light-responsive nanoparticles for doxorubicin delivery were developed. The nanoparticles were based on cleavable di-block copolymers of poly(ethylene glycol) (PEG) and poly(lactic acid) (PLA) linked by a red-light sensitive segment (1,2-bis(2-hydroxyethylthio)ethylene, BHETE). The PEG-BHETE-PLA copolymers were synthesized under mild conditions and exhibited a narrow polydispersity. The nanoparticles presented a size between 53 and 133 nm, with a doxorubicin loading capacity between 1.2 and 4.4 wt%. Release study of the encapsulated doxorubicin confirms the light-triggered nanoparticle disassembly process. In vitro cytotoxicity tests in MCF7 cell line, for the light-triggered nanoparticles, showed a decrease in cancer cells' viability higher than 25% compared to non-irradiated cells. Due to the promising results obtained with the light-sensitive PEG-BHETE-PLA nanoparticles, these materials have great potential to be used in drug delivery systems for cancer therapy.

Near infrared light-triggered nanoparticles using singlet oxygen photocleavage for drug delivery systems.

Drug delivery systems (DDSs) have showed a reduced systemic toxicity and enhanced therapeutic efficacy over conventional cancer treatments. However, after reaching the damaged tissue, DDSs should present a trigger release of the encaged therapeutics. Among all methodologies for a controlled release system, the use of light in NIR window (650-900 nm) shows the most appropriate characteristics for biological applications (e.g. biocompatibility with tissues). This review is focused on NIR responsive approaches for DDSs intermediated by a photosensitizer (PS) using nanoparticles (NP) that possess oxidation sensitive segments. After excited by light, the PS generates singlet oxygen species which interact with a sensitive segment, causing bond cleavage or hydrophobicity change in NP followed by the release of entrapped therapeutics. The most relevant sensitive segments addressed in this work are: olefin (lipid, vinyl ether, vinyl disulfide, and aminoacrylate), thioketal, selenium and hydrophobicity changeable polymers (tellurium, poly(propylene sulfide), imidazole and nitroimidazole). The chemical structure of the sensitive segment, the available strategies for nanoparticle formation and DDSs in vitro and in vivo studies are also critically discussed. These NIR responsive DDSs have enormous potential as a tool for a controlled spatial-temporal drug release with capacity to overcome the drawbacks of the others specificity target DDSs (such as pH, temperature and ROS). In order to reach the pharmacological market, the light sensibility of the labile segments should increase for the range of wavelengths used and more biological test should be addressed.