An NIR-Guided Aggregative and Self-Immolative Nanosystem for Efficient Cancer Targeting and Combination Anticancer Therapy

Abstract

Nanosized drug delivery systems based on polymeric structures have been proven to be promising approaches for cancer treatments. However, few have been effective at selectively targeting cancer cells and releasing drug at desired tumor sites. Here, we report a “smart” polymeric nanoplatform, which could actively accumulate at tumor sites and dissociate to release encapsulated cargos upon the irradiation of a near-infrared (NIR) laser. This nanoplatform composed of a novel amphiphilic block copolymer poly­(propylene sulfide)-poly­(N-iso­propyl­acryl­amide-co-N,N-di­methyl­acryl­amide) (PPS-P­(NIPAM-co-DMAA)) formed spherical structures in aqueous solution and responded to both oxidants and elevated temperature. Upon laser irradiation at 808 nm, the NIR light was efficiently converted to local heat by the doxorubicin (DOX) and indocyanine green (ICG) co-loaded micelles for enhanced cell uptake and therapeutic efficacy. It showed that the micelles effectively accumulated at the tumor sites guided by the application of an NIR laser in in vivo studies, exhibiting a 6-time greater and much faster targeting effect compared to the nonirradiation group. The effective tumor growth inhibition by the drug-loaded micelles upon laser irradiation demonstrated significant tumor inhibition without regrowth in 16 days. This micellar nanoplatform for precise NIR-guided cancer targeting and combination therapy provides a novel and robust strategy for cancer therapy.

Switching of the Polarity-Sensitive Aggregation Pattern of a Thiosemicarbazone-Based Anticancer Luminophore and Its Involvement in Cellular Apoptosis of the Human Lung Cancer Cell Line

“…Over recent years, the scientific community has come up with strikingly potential and innovative solutions to provide targeted therapy using single-molecular theragnostic platforms combining the benefits of real-time diagnosis and therapy to cancer patients. , The worth of small molecules that can simultaneously image and deliver therapeutic activity is momentous; such an approach can provide an insight into its uptake, distribution, and therapeutic action. − These therapeutic entities carry impending potential to undo the problems accompanying biodistribution and selectivity with a long-term hope of providing personalized medicine . Theragnostic agents can reach the target site and interfere with the activity of specific biomolecules, thereby inhibiting the growth of tumor cells. , It is to be emphasized that harmony between the above-mentioned two different physiological parameters depends on the environmental perturbation emission signals from localized bioactive luminophores.…”

“…3−5 These therapeutic entities carry impending potential to undo the problems accompanying biodistribution and selectivity with a long-term hope of providing personalized medicine. 6 Theragnostic agents can reach the target site and interfere with the activity of specific biomolecules, thereby inhibiting the growth of tumor cells. 7,8 It is to be emphasized that harmony between the above-mentioned two different physiological parameters depends on the environmental perturbation emission signals from localized bioactive luminophores.…”

Oxidation-Responsive Micelles for Drug Release Monitoring and Bioimaging of Inflammation Based on FRET Effect in vitro and in vivo

“…As shown in Scheme 1 , we firstly synthesized an amphiphilic diblock copolymer PPS-mPEG via a living anionic polymerization process. 19 , 20 Polypropylene sulfide (PPS) is a type of well-studied hydrophobic oxidation-responsive polymer, which can consume intracellular ROS and transformed to more hydrophilic polypropylene sulfoxide or sulfone due to the oxidation of the sulfur atoms on the polymer backbone. 12 , 21 Dansyl and dabsyl groups were conjugated to the amino groups of the polymer to form a fluorescent donor DAN-PPS-mPEG and its quencher DAB-PPS-mPEG.…”