Second near-infrared photoactivatable biocompatible polymer nanoparticles for effective in vitro and in vivo cancer theranostics.

Photoacoustic imaging (PAI)-guided photothermal therapy (PTT) has drawn considerable attention due to the deeper tissue penetration and higher maximum permissible exposure. However, current phototheranostic agents are greatly restricted by weak absorption in the second near-infrared (NIR-II, 1000-1700 nm) window, long-term toxicity, and poor photostability. In this report, novel organic NIR-II conjugated polymer nanoparticles (CPNs) based on narrow bandgap donor-acceptor BDT-TBZ polymers were developed for effective cancer PAI and PTT. Characterization data confirmed the high photothermal conversion efficiency, good photostability, excellent PAI performance, and superior biocompatibility of as-obtained CPNs. In addition, in vitro and in vivo tests demonstrated the efficient PTT effect of CPNs in ablating cancer cells and inhibiting tumor growth under 1064 nm laser irradiation. More importantly, the CPNs exhibited rapid clearance capability through the biliary pathway and negligible systematic toxicity. Thus, this work provides a novel organic theranostic nanoplatform for NIR-II PAI-guided PTT, which advances the future clinical translation of biocompatible and metabolizable conjugated nanomaterials in cancer diagnosis and therapy.

Highly absorbing multispectral near-infrared polymer nanoparticles from one conjugated backbone for photoacoustic imaging and photothermal therapy.

Semiconducting polymers with specific absorption are useful in various applications, including organic optoelectronics, optical imaging, and nanomedicine. However, the optical absorption of a semiconducting polymer with a determined structure is hardly tunable when compared with that of inorganic semiconductors. In this work, we show that the optical absorption of polymer nanoparticles from one conjugated backbone can be effectively tuned through judicious design of the particle morphology and the persistence length of polymers. Highly absorbing near-infrared (NIR) polymers based on diketopyrrolopyrrole-dithiophene (DPP-DT) are synthesized to have different molecular weights (MWs). The DPP-DT polymer with a large molecular weight and high persistence length exhibited remarkably high optical absorption with a peak mass extinction coefficient of 81.7 L g-1 cm-1, which is one of the highest value among various photothermal agents reported to date. Particularly, the polymer nanoparticles with different sizes exhibit broadly tunable NIR absorption peaks from 630 to 811 nm. The PEGylated small polymer dots (Pdots) show good NIR light-harvesting efficiency and high non-radiative decay rates, resulting in a relatively high photothermal conversion efficiency in excess of 50%. Thus, this Pdot-based platform can serve as promising photothermal agents and photoacoustic probes for cancer theranostics.

Enhanced Phototherapy by Nanoparticle-Enzyme via Generation and Photolysis of Hydrogen Peroxide.

Light has been widely used for cancer therapeutics such as photodynamic therapy (PDT) and photothermal therapy. This paper describes a strategy called enzyme-enhanced phototherapy (EEPT) for cancer treatment. We constructed a nanoparticle platform by covalent conjugation of glucose oxidase (GOx) to small polymer dots, which could be persistently immobilized into a tumor. While the malignant tumors have high glucose uptake, the GOx efficiently catalyzes the glucose oxidation with simultaneous generation of H2O2. Under light irradiation, the in situ generated H2O2 was photolyzed to produce hydroxyl radical, the most reactive oxygen species, for killing cancer cells. In vitro assays indicated that the cancer cells were destroyed by using a nanoparticle concentration at 0.2 µg/mL and a light dose of ∼120 J/cm2, indicating the significantly enhanced efficiency of the EEPT method when compared to typical PDT that requires a photosensitizer of >10 µg/mL for effective cell killing under the same light dose. Furthermore, remarkable inhibition of tumor growth was observed in xenograft-bearing mice, indicating the promise of the EEPT approach for cancer therapeutics.